PIPERAZINE DERIVATIVES AND THEIR USE AS ANTI-INFLAMMATORY AGENTS

Abstract: This invention is directed to acyl piperazine derivatives which are useful as anti-inflammatory agents. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat inflammatory disorders in humans.

Description: PIPERAZINE DERIVATIVES AND THEIR USE AS ANTI-INFLAMMATORY AGENTS Field of the Invention The present invention is directed to piperazine derivatives and their pharmaceutically acceptable salts, which inhibit the activity of the chemokines, MIP-1 α and RANTES, thereby being useful as anti-inflammatory agents It also relates to pharmaceutical compositions containing the derivatives or their pharmaceutically acceptable salts, and methods of their use BACKGROUND OF THE INVENTION An important component of the inflammatory process involves the migration and activation of select populations of leukocytes from the circulation and their accumulation in the affected tissue. While the lαea of leukocyte trafficking is not new, it has enjoyed a renaissance recently following the discovery and characterization of the selectin and integnn families of adhesion molecules and the large family of selective chemotatic cytokines known as chemokines Chemokme receptors are expressed on leukocytes and process the signals following the binding of the chemokme whereDy such signals are eventually transduced into migration or activation of the leukocytes towards the source of the chemokme Therefore, by regulating the migration and activation of leukocytes from the peripheral blood to extravascular sites in organs, skin, articulations or connective, tissue, chemokines play a critical role in the maintenance of host defense as well as in the development of the immune response Originally, the chemokme family of molecules was divided into two groups the "C-X-C" subfamily and the "C-C" subfamily The characteristic feature of both of these subfamilies is the presence of four cysteine residues in highly conserved positions in the molecules. In the "C-C" chemokme subfamily, the first two residues are adjacent to each other, while in the "C-X- C" subfamily, the cysteine residues are separated by a single ammo acid residue A recent description of a "-C-" chemokme appears to represent a new family of chemokines in that the "- C" chemokme lacks two of the four cysteine residues present in the "C-C" subfamily or the "C- X-C" subfamily. One member of the "C-C" subfamily of chemokines is macrophage inflammatory proteιn-1 ("MIP-1 α"). It is expressed by cells such as macrophages, T and B lymphocytes, neutrophils and fibroblasts. A recent study (see Karpus, W.J. ef al., J. Immunol. (1995), Vol. 155, pp. 5003-5010) provides strong in vivo concept validation for a rote of MIP-1 α in a mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Multiple sclerosis is an autoimmune disease mediated by T and B lymphocytes and macrophages, resulting in extensive inflammation and demyelination of white matter in the central nervous system. The study showed that antibodies to MIP-1 α prevented the development of both initial and relapsing disease as well as preventing the infiltration of mononuclear cells into the central nervous system Treatment with the antibodies was also able to ameliorate the severity of ongoing clinical disease These results led the investigators to conclude that MIP-1 α plays an important role in the etiology of multiple sclerosis In addition, another study (see Godiska, R et al., J. Neuroimmunology (1995), Vol. 58, pp 167-176) demonstrated an upregulation of mRNA for a number of chemokines, including MIP-1 , in the lesions and spinal cord of SJL mice (a strain of mice susceptible to Th^ diseases such as EAE) during the course of acute EAE RANTES is another member of the C-C chemoKine subfamily (the name RANTES is an acronym derived from some of the original ODserveo and predicted characteristics of the protein and its gene Regulated upon Activation Normal I cell Expressed presumed Secreted) A wide variety of tissues have been found to express RANTES in a similar pattern to MIP-1 Strong evidence exists linking RANTES to organ transplant rejection, particularly of the kidney The infiltration of mononuclear cells into the interstitium of organ transplants is the hallmark of acute cellar rejection This cellular infiltrate primarily consists of T cells, macrophages and eosinophils. In a study of RANTES expression during acute renal allograft rejection, RANTES mRNA expression was found in infiltrating mononuclear cells and renal tubular epithelial cells and RANTES itself was found to be bound to the endothelial surface of the mtcrovasculature within the rejecting graft (see Pattison, J. et al . Lancet (1994), Vol. 343, pp. 209-211 and Wieαermann, CJ. et al., Curr. Biol. (1993), Vol. 3, pp. 735-739). There is also evidence from a number of studies to implicate the abnormal production of RANTES in the progression of rheumatoid arthritis (see Rathanaswami, P ef al., J. Biol. Chem (1993), Vol. 268, pp. 5834-5839 and Snowαen, N ef al., Lancet (1994), Vol. 343, pp 547-548) Rheumatoid arthritis is a chronic inflammatory disease characterized in part by a memory T lympnocyte and monocyte infiltration, which is believed to be mediated by cnemotactic factors released by inflamed tissues In addition, there is strong evidence from other studies implicating RANTES in the pathophysiology of rheumatoid arthritis (see Barnes, D.A ef al., J. Clin. Invest (1998, in press) and Ptater-Zyberk, C A. ef al , Immunol Lett (1997), Vol 57, pp. 117-120) For example, in an adjuvant-induced arthritis (AIA) model in the rat, antibodies to RANTES greatlv reduced the development of disease in rats induced for AIA These studies and others provide strong evidence tnat MIP-1 α levels are increased in EAE models ot multiple sclerosis and that RANTES levels are increased in rneumatoid artnritis and kioney transplant rejection (see, e g , Glabinski, A R et al , Am J Pathol (1997), Vol 150, pp. 617-630, Glabmski, A R ef al , Methods Enzymol (1997), Vol 288, 182-190, and Miyagishi, R S ef al , J Neuroimmunol (1997), Vol 77, pp 17-26) In addition, as described above, these chemokines are chemoattractants for T cells and monocytes wnich are the major cell types that are involved in the pathophysiology of these diseases Therefore, any molecule that inhibits the activity of either of these cnemokines would be beneficial in treating these diseases and would therefore be useful as an antι-ιnτιammatory agent Related Disclosures Piperazine derivatives of the type similar to the compounds of the invention are known in the literature as being useful for a variety of pharmaceutical indications, particularly as cardiotonic, neurotropic or anti-inflammatory agents For example, published European Patent Application 0 702 010 (Adir) describes certain piperazine derivatives as being useful as central nervous system depressants and in the treatment of Alzheimer's and other diseases of immunological origin, such as arthritis and intestinal peπstaltism Published European Patent Application 0 655 442 (Fujisawa) describes similar piperazine derivatives as tachykmin antagonists useful in treating inflammatory diseases sucn as rheumatoid arthritis and osteoarthπtis A Czech published patent application, 260089, and related article, Valenta, V ef al., Collection Czechoslovak Chem. Commun (1987), Vol. 52, pp. 3013-3023, disclose piperazine derivatives as potential neurotropic and cardiovascular agents. European Published Patent Application 0 252 422 (Mitsubishi) and German Published Patent Application 3614363 (Hoechst) describe piperazine derivatives as being useful as cardiotonic agents. European Published Patent Application 0 190 685 (G.D. Searle) describes piperazine derivatives which block the 5-lιpoxygenase pathway of the arachidonic acid cascade, thereby being useful in the treatment of allergic and hypersensitivity reactions and inflammation. PCT Published Patent Application, WO 96/34864 (Schenng Plough) discloses piperazine derivatives useful as neurokinm antagonists. All of the above references are incorporated herein in full by reference. None of the aDove references describe the piperazine derivatives described herein or their usefulness in treating infiammatorv disorders in numans by inhibition of the activity of the chemokines. MIP-1 α and RANTES SUMMARY OF THE INVENTION This invention is directed to compounds or their pharmaceutically acceptable salts which inhibit the activity of the chemokines, MIP-1 α and RANTES and are therefore useful as pharmacological agents for the treatment of inflammatory disorders in humans. Accordingly, in one aspect, this invention provides compounds of the following formula (la): wherein: R 1a is one or more substituents independently selected from the group consisting of oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycloalkylaminoalkyl, (cycloalkyialkyl)amιnoalkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl, formylaikyl, hydroxyalkyl, hydroxyalkenyl, hydroxyatkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloatkylcarbonyiaminoalkyl, (alkoxy)aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsutfinylalkyl, alkylsulfoπylaikyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoaikyl, (alkoxycarbonylalkyl)ureιdoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyloxyalkyl, alkoxyalkylcarbonyloxyalkyl, aralkoxyalkylcarbonyioxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylamiπocarbonyl, carboxyalkyl, alkoxycaroonylalkyl, aralkoxycarbonylalkyl, aminocaroonylalkyl. monoalkylaminocaroonylalkyl. dialkylaminocarbonvlalkyl, monoarylaminocarponylalkyi, monoaralkylaminocaroonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulf yl, alkylsufonyl, alkylthioalkyl, alkvlsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano. aralkoxy. naloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxyjcycloalkylalkyl, cycloalkylamino, cycloalkvlaminoalkyl, (cycloalkylalkyl)amιno, (cycloalkyalkyl)amιnoalkyl, cyanoalkyl. alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxyiaralkyl, hydroxyalkylthioalkyl, hydroxyaikenyl, hvdroxyalkynyl, aikoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl aralKoxvalkyl, ammo monoalkylamino. dialkylamino, monoarylamino, moπoaralkyiamino. am oalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammo, (alkylcarbonyl)(alkyl)amιno, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylammo, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl. carboxy. alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl. alkoxycaroonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, aminocarbonylalkyl, monoalkylammocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidmo, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl. dialkylureidoalkyl, heterocyciyl and heterocyclylalkyl; R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfiπyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinyialkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, aminoaikoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylamino, cycloalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkylaminoiaraikyl, (hydroxvalkyl)hιoalkyl, hyoroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy laralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylammo. dialkylamiπo, monoaryiamino, monoaralkylamino, aminoalkylamino. heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxvcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylammo, haloalkylcarbonylammo, alkoxyalkylcarbonyiamino. alkoxycarbonylalkylcarbonyiamino. (alkylcarboπyl)(alkyl)amιno, (alkoxycarDonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl alkyicaroonyiaminoalkyl, arylcarbonyiaminoalkyl, (alkvlcarbonyD(alkyl )amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycaroonvlalkvlcarDonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyl, arylsulfonylaminoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarboπyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcaroonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylaminocarbonyl, (amιnocarbonyialkyl)amιnocarbonyl, (monoalkylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonylalkyl)amιnocarbonyl, (amιnoaikyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, ammocarbonylalkyl, monoaikylam ocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylaminocarbonylalkyl, amidino, hydroxyamidmo, guanidino, ureido, monoalkylureido, monoarylureioo, monoaralkylureido, monohaloaikylureido, (monoaikyl)(monoaryl)ureιdo, dialkylureido. diarylureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcaroonyl)giycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcaroonyl)glycιnamιdo. arylcarbonyiglycinamido, (arylcarDonyl)(alkyl)giycιnamιoo, (monoaralkyiamιnocaroonyl)glycιnamιdo, (monoaralkylammocaroonyl)(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιπocaroonyl)(alkyl)glycιnamιdo, glycinamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, or R 3 is a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, naloalkyl formyl nitro, cyano, haloalkoxy, alkenyl, aikynyl, aryl, aralkyl, ammo, monoalkylamino αialkylamino, monoarylammo, monoaralkylamino, alkylcaroonyiamino. aiκoxvcaroonviamιno. alkenylcarbonylamino cycloalkylcaroonylamino, aryicarponviamino naloalkyicaroonvlamino, alkoxyaikylcaroonylammo, alkoxycaroonylalkylcaroonyiamino, (alkylcarbonyl)(alkyl)amιno, (alkoxycaroonyl)(alkyl)amιno, alkylsulfoπyiamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycaroonyi, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, guanidino. ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido; R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond; R 5 is an alkylene cnaiπ or an alkylidene cnam, or, if R 4 is a bond, R is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2 , R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond; each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarDonyl; and each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylamino, aikylcarbonylammo, cycloalkylcaroonylamino, cycloalkylalkylcarbonylamino, alkoxvcaroonyiamino, alkylsulfonviamino, arvlcarbonylamiπo. alkoxycaroonylalkylcarbonylamino (alkylcaroonyl)(alkyl)amιno, aralkylcarbonyiamino, (aralkylcaroonyl)(alkyl)amιno. alkylcarbonylammoalkyl, cycloalkylcaroonylaminoalkyl, alkoxycaroonylammoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, aralkylcaroonylaminoalkyl, heterocyclyicarbonylaminoalkyl, (aralkyicarbonyl)(alkyl)ammoalkyl, arylsulfonylamino, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkyluretdo. dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureiooalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl. carboxyalkyl, alkoxycaroonylalkyl, aminocaroonylalkyl, monoalkylaminocarbonvlalkyl and dialkyiaminocaroonylalkyl, provided that when R 4 is -N(R' )-, R 3 can not be a heterocyclic ring system containing 4-8 memoers consisting of caroon atoms ano oniv one nitrogen atom, and as a single stereoisomer or a mixture thereof, or a pnarmaceutically acceptable salt thereof In another aspect, this invention provides pnarmaceutical compositions useful in treating an inflammatory disorder in a human in need of sucn treatment, whicn composition comprises a therapeutically effective amount of a compound of formula (la) as described above, and a pharmaceutically acceptabe excipient In another aspect, this invention provides a method of treating an inflammatory disorder in a numan, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (la) as described above In another aspect, this invention provides pharmaceutical compositions useful in treating an inflammatory disorder in a humar in need of such treatment, which composition comprises a therapeutically effective amount of a compound of formula (lb): wherein R 2 , R 3 , R 4 , R 5 and R 6 are the same as described above for compounds of formula (la), and a pharmaceutically acceptable excipient In another aspect, this invention provides a method of treating an inflammatory disorder in a numan, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) as described above In another aspect, this invention provides compounds of the following formula (lc) wherein R 2 , R 3 , R 4 , R 5 and R° are the same as described aoove for the compounds of formula (la), Y is a pharmaceutically acceptable counteπon R 1b is one or more substituents independently selected from the group consisting of hydrogen, oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycloalkylaminoalkyl, (cycloalkylalkyl)amιnoalkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hyoroxy)aralkyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcaroonyiaminoalkyl, (alkoxy)aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsuifonylalkyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkylcarbonyi)(alkyl)amιnoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarDonylalkyl)ureιdoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarDoπyloxyalkyl, alkoxyalkylcarbonyloxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcaroonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylaminocarbonyl, carboxyalkyl, alkoxycaroonylalkyl, aralkoxycaroonylalkyl, aminocarbonylaikyl, monoalkylaminocaroonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl; and R 9 is alkyl, aralkyl, haloalkyl, hvdroxvalkyl. aiKoxvalkyl. carooxyalkyl, alkoxycaroonylalkvl, alkylcarbonylalkyl, alkylcarbonylammoalkyl, aminocaroonylalkyl, monoalkylaminocarbonylalkyl, dialkylammocaroonylalkyl, hetereocyclylalkyl, or cycloalkylalkyl; as a single stereoisomer or a mixture thereof: or a pharmaceutically acceptable salt thereof. In another aspect, this invention provides a pharmaceutical composition useful in treating an inflammatory disorder, which composition comprises a therapeutically effective amount of a compound of formula (lc) as descrioed above, and a pharmaceutically acceptable excipient. In another aspect, this invention provides a metnoo of treating an inflammatory disorder in a numan, which method comprises administration to a numan in need thereof of sucn treatment of a therapeutically effective amount of a compound of formula (lc) as described above. In another aspect, this invention provides compounds of the following formula (Id). wherein: R 3 , R 4 , R 5 and R 6 are the same as described above for the compounds of formula (la); R 1 is one or more substituents independently selected from the group consisting of oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycloalkylam oalkyl, (cycloalkylalkyl)amιnoalkyl, haloalkyl, alkenyl, alkyπyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylammoalkyl, (alkoxy)aralkyl. alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylaikyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyi)amιnoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarPonylalkyl)ureιooalkyl. aikoxycaroonylaminoalkyl, hydroxyalkylammoalkyl, aryioxyalkylcarbonyioxyaikyl, alkoxyalkylcaroonyioxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonyl. alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl. dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylaminocaroonyl, carboxyalkyl. alkoxycaroonylalkyl. aralkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylaminocaroonylalkyl, monoaralkylaminocarponylalkyl. arylsulfonyl, heterocyclyl and heterocyciylalkyl; and R 10 is a heterocyclyl optionally substituted by one or more suostituents selected from the group consisting of hydroxy, mercapto, halo. alκyl. alkenyl. alkyπyl. phenyl, pnenylalkyl, phenylalkenyl, alkoxy, pnenoxy, phenylalkoxy, haloalkyl, naloalkoxy, formyl, nitro, cyano, amidino, cycloalkyl, hydroxyalkyl, alkoxyalkyl, phenoxyalkyl, phenylalkoxyalkyl, am o, monoalkyiamino, dialkylamino, monophenylamino, monophenylaikylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monophenylaminoalkyl, monophenylalkylammoalkyl, carboxy, alkoxycarbonyl, phenyicarbonyl. benzylcarbonyl, alkylcarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, phenylaminocarbonyl, ammocarbonylalkyl, monoalkylaminocarooπylalkyl, dialkylaminocarbonylalkyl, ureido, monoalkylureido, monophenylureido, and monobenzylureido; as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof. In another aspect, this invention provides a pnarmaceutical composition useful in treating an inflammatory disorder in a human in need of such treatment, which composition comprises a therapeutically effective amount of a compound of formula (Id), as described above, and a pharmaceutically acceptable excipient. In another aspect, this invention provides a method of treating an inflammatory disorder in a human, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (Id) as described above. DETAILED DESCRIPTION OF THE INVENTION Definitions As used in the specification and appended claims, unless specified to the contrary, the following terms have the meaning indicated' "Alkyl" refers to a straight or brancned chain monovalent or divalent radical consisting solely of carbon and hydrogen, containing no unsaturation and having from one to eight carbon atoms, e.g., methyl, ethyl, π-propyl, 1-methylethyl (/so-propyl), π-butyl, π-pentyl, 1 ,1-dιmethylethyl (f-butyl), n-heptyl, and the like "Alkylcarbonyl" refer to a radical of the formula -C(0)-R 3 where R a is an alkyl radical as defined above, e.g., acetyl, ethylcarbonyi, n-propyicarbonyl, and the like "Alkylcarbonylalkvl" refers to a radical of the tormuia -R a -C(O R a where each R a is independently an alkyl radical as defined above e g (acetvl .methyl, 2-(acetvl)ethyl, 4-(ethylcarbonyl)butyl, and the like. "Aikylcarbonylammo" refers to a radical of the formula -N(H)-C(0)-R a wnere R a is an alkyl radical as defined above, e.g., acetylamino, ethylcarbonylamino, π-propyicarbonylamino and the like. "(Alkylcarbonyl)(aikyl)amιno" refers to a radical of the formula -N(R a )-C(0)-R a where each R a is independently an alkyl radical as defined above, e.g., Λ/-methyl-Λ/-acetylamιno, Λ/-ethyl-Λ/-(ethylcarbonyl)amιno, and the like "Alkylcarbonylammoalkyl" refers to a radical of the formula -R a -N(H)C(0)-R a where each R a is independently an alkyl radical as defined above, e.g., acetylaminomethyl, 2-(acetylamιno)ethyl, 4-(ethylcaroonylamιno)butyl, and the like "(AlkylcarDonyl)(alkyl)amιnoaikyl" refers to a radical of the formula -R a -N(R a )-C(O)-R a where each R a is independently an alkyl radical as defined above, e.g., (Λ/-methyl-Λ/- acetylamιno)methyl, 2-(Λ/-ethyl-/V-(ethylcarbonyl)amιno)propyl, and the like. "Alkylthio" refers to a radical of the formula -S-R a where R a is an alkyl radical as defined above, e.g., methylthio, ethylthio. π-propylthio, and the like. "Alkylsulfinyl" refers to a radical of the formula -S(0)R a where R a is an alkyl radical as defined above, e.g , methylsulfmyl, ethylsulfmyl, π-propylsulfinyl, and the like "Alkylsulfonyl" refers to a radical of the formula -S(0) 2 R a where R a is an alkyl radical as defined above, e g , methylsulfonyl, ethylsulfonyi, n-propylsulfonyl, and the like "Alkylthioalkvl" refers to a radical of the formula -R a -S-R a where each R a is independently an alkyl radical as defined above, e g methylthiomethyl, 2-methylthιoethyl, 2-ethylthιopropyl, and the like "Alkylsulfmylalkyl" refers to a radical of the formula -R a -S(0)-R a where where each R a is independently an alkyl radical as defined above, e g , methylsulfinylmethyl, 2-methylsulfιnyiethyl, 2-ethylsulfιnylpropyl, and the like "Alkylsulfonylalkyl" refers to a radical of the formula -R a -S(0) 2 -R a where each R a is independently an alkyl radical as defined above, e g methylsulfonyimethyl, 2-methylsulfonylethyl, 2-ethylsuifoπylpropyl, and the like "Alkylsulfonyiamino" refers to a radical of the formula -N(H)-S(0) 2 -R 3 where R a is an alkvi radical as defined above, e g , methylsultonviamino ethylsulfonviamino. iso- propylsulfonylamino, and the iike. "Alkylsulfonylammoalkyl" refers to a radical of the formula -R a -N(H)-S(0) 2 -R a where each R a is independently an alkyl radical as defined above, e.g , methylsulfonylammomethyl, 2-(ethylsulfonylamιno)ethyl, 3-(.so-propylsulfonylamιno)propyl, and the like "(Alkylsulfoπyl)(alkyl)amιnoalkyl" refers to a radical of the formula -R a -N(R a )-S(0) 2 -R a where each R a is independently an alkyl radical as defined above, e.g., (methylsulfonyl)(methyl)amιnomethyl, 2-((ethylsulfonyl)(methyl)amιno)ethyl, 3-((/so- propylsulfonyl)(ethyl)amιno)propyl, and the like. "Alkenyl" refers to a straight or branched chain monovalent or divalent radical consisting solely of carbon and hydrogen, containing at least one double bond and having from two to eight carbon atoms, e.g., ethenyl, prop-1-enyl, but-1-enyl, pent-1-enyl, penta-1 ,4-dιenyl, and the like. "Alkenylcarbonylamino" refers to a radical of the formula -N(H)-C(0)-R c where R c is an alkenyl radical as defined above, e.g., ethenylcarbonylamino, prop-2-enylcarbonylamιno, but-2- enylcarbonylamino, and the like. "Alkynyl" refers to a straight or branched chain monovalent or divalent radical consisting solely of carbon and hydrogen, containing at least one triple bond and having from two to eight carbon atoms, e.g., ethynyl, prop-1-ynyl, but-1-ynyl, pent-1-ynyl, pent-3-ynyl, and the like "Alkoxy" refers to a radical of the formula -OR a where R a is an alkyl radical as defined above, e.g., methoxy, ethoxy, π-propoxy, 1 -methylethoxy (/so-propoxy), π-butoxy, π-oentoxy 1 ,1 -oιmethylethoxy (f-butoxy), and the like "Alkoxycarbonyl" refers to a radical of the formula -C(0)OR a wnere R a is an alkyl radical as defined above, e.g., methoxycarbonyl, ethoxycarbonyl, π-propoxycarbonyl, and the like "Alkoxycarbonylalkyl" refers to a radical of the formula -R a -C(0)OR a where each R a is independently an alkyl radical as defined above, e g , methoxycarDonyimethyl, 2-(ethoxycaroonyl)ethyl, 2-(methoxycarbonyl)propyl, and the like. "Alkoxyalkylcaroonyloxyalkyl" refers to a radical of the formula -R a -OC(0)-R a -OR a wnere each R a is independently an alkyl radical as defined above, e.g , metnoxymethylcaroonyloxymethyl, 2-(2-(2-(ethoxy)ethvlcarbonyloxy)ethvl)ethyl, 2-(3-(2- (ethoxy)ethylcarbonyioxy)propyl)ethyl, and the like "Alkoxycarbonylamino" refers to a radical of the formula -N(H)-C(0)-OR a wnere R a is an alkyl radical as defined above, e.g., methoxycaroonylaminα, ethoxycarbonylamino, /sopropoxycarbonylamino, and the like. "(Alkoxycarbonyl)(alkyl)amιno" refers to a radical of the formula -N(R a )(C(0)OR a ) where each R a is independently an alkyl radical as defined above, e.g., Λ/-methyl-/V- methoxycarbonylammo, A/-ethyl-Λ/-ethoxycarbonylamιno, and the like "Alkoxycarbonylaminoalkyl" refers to a radical of the formula -R a -N(H)-C(0)-OR a wnere each R a is independently an alkyl radical as defined above, e.g., metnoxycarbonylammomethyl, 2-(ethoxycarbonylamιno)ethyl, /sopropoxycarbonylaminomethyl, and the like. "(Alkoxycarbonyl)(alkyl)amιnoalkyl" refers to a radical of the formula -R a - N(R a )(C-(0)OR a ) where each R a is independently an alkyl radical as defined above, e.g., Λ/-methyl-Λ-methoxycarbonylamιnomethyl, 2-(Λ/-ethyl-Λ/-ethoxycarbonyiamιno)ethyl, and the like. "(Alkoxy )aralkyl" refers to an aralkyl radical wherein the alkyl group therein is substituted by an alkoxy radical as defined above, e.g., 2-phenyl-1-methoxyethyl, phenyi(methoxy)methyl, "Alkoxyalkylcarbonylamino" refers to a radical of the formula -N(H)-C(O)-R a -0-R a where each R a is an alkyl radical as defined above, e.g., methoxymethyicarbonylamino, ethoxyethylcarbonylamino, methoxyethylcarbonylamino, and the like. "Alkoxycarbonylalkylcarbonylamino" refers to a radical of the formula -N(H)-C(0)-R a -C(0)OR a wnere each R a is independently an alkyl radical as defined above, e g ethoxycaroonylmethylcarbonylamino methoxvcaroonyimethylcarbonylammo, (2-ethoxycarbonylethyl)carbonylamιno, (2-methoxycarbonylethyl)carbonylamιno, and the like "Alkoxycarbonylalkylcarbonylaminoalkyl" refers to a radical of the formula -R a -N(H)-C(0)-R a -C(0)OR a where each R a is independently an alkyl radical as defined above e.g., ethoxycarbonylmethylcarbonylammomethyl, 2-(methoxycarbonylmethylcarbonylamιno)ethyl, 1 -((2-ethoxycarDonylethyl)carboπylamιno)ethyl, (2-methoxycarbonylethyl)carbonylamιnomethyl, and the like "(Alkoxycarboπylalkyl)amιnocarbonyl" refers to a radical of the formula -C(0)-N(H)-R a - C(O)-OR a where each R a is independently an alkvl radical as defined above, e g , (methoxycaroonylmethyl)ammocaroonyl, (2-(etnoxvcaroonyl)ethyhamιnocaroonyl (1 - (methoxycarbonyl)ethyl)amιnocarbonyl, and the like "(AlkoxycarDonylalkyl)ureιdoalkyl" refers to a radical of the formula -R a -N(H)-C(0)-N(H)- R a -C(0)-OR a where each R a is independently an alkyl radical as defined above and where the nitrogen to which -R a -C(0)-OR a is attached is indicated as "N", e g , (ethoxycarbonylmethyl)ureιdomethyl, (2-(ethoxycarbonyl)ethyl)ureιoomethyl, 2-((2- (ethoxycarbonyl)ethyl)ureιdo)ethyl, and the like "(Alkoxycarbonylalkylcaroonyl)(alkyl)glycιπamιdo" refers to a radical of the formula -N(H)-C(O)-CH 2 -N(R a )-C(O)-R a -C(0)-OR a where each R a is independently an alkyl radical as defined above, e.g., (methoxycaroonyimethylcarbonyl)(methyl)glycιnamido, ((2-ethoxycarbonylethyl)carbonyl)(ethyi)glycιnamιdo, and the like. "(Alkoxyalkylcarbonyl)glycιnamido" refers to a radical of the formula -N(H)-C(0)-CH 2 - N(H)-C(O)-R a -0-R a where each R a is independently an alkyl radical as defined above, e.g., (methoxyacetyl)glycιnamιdo, (ethoxyacetyl)glycιnamido, and the like. "Alkylene chain" refers to straight or branched chain divalent radical consisting solely of carbonyl and hydrogen, containing no unsaturation and having from one to eight carbon atoms, e.g., methylene, ethylene, propylene, π-butylene, and the like. "Alkylidene chain" refers to a straight or branched chain unsaturated divalent radical consisting solely of carbon and hydrogen atoms, having from one to eight caroon atoms, wherein the unsaturation is present only as double oonds and wherein a double bond can exist between the first carbon of the cnain and the rest of the molecule, e.g., ethylidene, propylidene, π-butylidene, and the like. "Ammo" refers to the radical -NH 2 . "Ammoalkyl" refers to a radical of the formula -R a NH 2 wnere R a is an alkyl radical as defined above, e.g., aminomethyl, 2-amιnoethyl, 3-amιnopropyl, 2-amιnopropyl, and the like. "Aminoalkyiamino" refers to a radical of the formula -N(H)-R a -NH 2 wnere R a is an alkyl radical as defined above, e.g., aminomethylammo, (2-amιnoethyl)amιno, (2-amιnopropyl)amιno, and the like. "Am oalkoxy" refers to a radical of a formula -OR π -NH 2 wnere R a is an alkyl radical as defined above, e.g., aminomethoxy, 2-amιnoethoxy, 3-amιnopropoxy, 2-amιnopropoxy, 4- ammobutoxy, and the like. "Aminocarbonyl" refers to the radical -C(0)NH 2 . "Aminocarbonylglycinamido" refers to a radical of the formula -N(H)-C(0)-CH 2 -N(H)- C(0)-NH 2 . "(Amιnocarbonyl)(alkyl)glycιnamido" refers to a radical of the formula -N(H)-C(0)-CH 2 -N(R a )-C(0)-NH 2 wnere R a is an alkyl radical as defined above and where the nitrogen with the R a substituent is designated as "N" , e.g., (amιnocarbonyl)(Λ '-methyi)glycιnamido, (amιnocarbonyl)(Λ/'-ethyl)glycιnamιoo, and the like. "Ammocaroonylalkyl" refers to a radical of the formula -R a -C(O)NH 2 where R a is an alkyl radical as defined above, e.g., aminccarooπylmethyl, 2-(amιnocarbonyl)ethyl, 2-(amιnocarbonyl)propyl, and the like. "(Amιnocarbonylalkyl)amιnocarbonyl" refers to a radical of the formula -C(0)-N(H)-R a - C(0)-NH 2 where R a is an alkyl radical as defined above, e.g., (amιnocaroonylmethyl)amιnocarbonyl, (2-amιnocarbonylethyl)amιnocarbonyl, (1- amιnocarboπylethyl)amιnocarbonyl, and the like. "(Amιnoalkyl)amιnocarbonyl" refers to a radical of the formula -C(0)-N(H)-R a -NH 2 where R a is an alkyl radical as defined above, e.g., (amιnomethyi)amιnocarbonyl, (2- amιnoethyl)amιnocaroonyl, (l -amιnoethyl)amιnocaroonyl, and the like. "Amidmo" refers to the radical -C(NH)NH 2 . "Aryl" refers to a phenyl or naphthyl radical. Unless stated otherwise specifically in the specification, the term "aryl" or the prefix "ar-" (such as in "aralkyl") is meant to include aryl radicals optionally substituted by one or more substituents selected from the group consisting of hydroxy, mercapto, halo, alkyl, alkenyl, alkynyl, phenyl, phenylalkyl, phenylalkenyl, alkoxy, phenoxy, phenylalkoxy, haloalkyl, haloalkoxy, formyl, nitro, cyano, amidmo, cycloalkyl, hydroxyalkyl, alkoxyalkyl, phenoxyalkyl, phenylalkoxyalkyl, am o, monoalkylamino, dialkylammo, monopnenylamino, monophenylalkylam o, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monophenyiaminoalkyl, moπophenylalkylaminoalkyl. alkylcarbonyl, carboxy, alkoxycarbonyl, carooxyalkyl. alkoxycarbonylalkyl. aminocarbonyl, monoalkylammocarbonyl dialkylaminocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, as defined herein. "Arylcarbonyl" refers to a radical of the formula -C(0)R b where R b is an aryl radical as defined above, e.g., phenylcarbonyl and naphthalen-2-ylcarbonyl, and the like. "Arylcarbonylaikyl" refers to a radical of the formula -R a C(0)R b where R a is an alkyl radical as defined above and R b is an aryl radical as defined above, e.g., phenylcarbonylmethyl, 2-(phenylcaroonyl)ethyl, 3-(naphthalen-2-ylcarbonyl)propyl, and the like. "Arylcarbonyiaminoalkyl" refers to a radical of the formula -R a -N(H)-C(0)-R where R a is an alkyl radical as defined above and R b is an aryl radical as defined above, e.g., (4- methoxyphenyl)carbonylamιnomethyl, 2-((4-fluorophenyl)carbony!amιno)ethyl, 1-((4- chlorophenyl)carbonylamιno)ethyl, and the like. "Arylsulfonyl" refers to a radical of the formula -S(0) 2 -R b where R b is an aryl radical as defined above, e.g., phenylsulfonyl, (4-chloropnenyl)sulfonyl, (3-nιtrophenyl)sulfonyl, and the like. "Arylsulfonylamino" refers to a radical of the formula -N(H)-S(0) 2 -R b where R b is an aryl radical as defined above, e.g , pheπylsulfonyiammo, (4-chlorophenyl)sulfonyiamιno, (4- fluorophenyl)sulfonylamιno, (3-nιtrophenyl)sulfonylamιno), and the like. "Arylsulfonylaminoalkyl" refers to a radical of the formula -R a -N(H)-S(0) 2 -R b where R a is an alkyl radical as defined above and R b is an aryl radical as defined above, e.g., phenylsulfonylaminomethyl, (4-chlorophenyl)sulfonylammomethyl, 2-((4- fluoropnenyl)sulfonylamino)ethyl 1 -((3-nιtropnenyl)sulfonvlamιno)ethyl, and the like "(Arylsulfonyl)(alkyl)amιnoalkyl" refers to a radical of the tormula -R a -N(R a )-S(0) 2 -R b where each R a is independently an alkyl radical as defined above and R b is an aryl radical as defined above, e.g., (phenylsulfonyl)(methyl)amιnomethyl, ((4-chlorophenyl)sulfonyl)(ethyl)amιnomethyl, 2-(((4-fluoropnenyl)sulfoπyl)(methyl)amιno)ethyl, 1-(((3-nιtrophenyl)sulfonyl)(ethyl)amιno)ethyl and the like "(Alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo" refers to a radical of the formula -N(H)-C(0)-CH 2 -N(H)-C(0)-N(H)-C(0)-OR a wnere R 3 is an alkyl radical as defined above, e g , (ethoxycarbonyiamιnocarbonyl)glycιnamιdo, (methoxycaroonylammocarbonyl)glycιnamιoo, and the like "Arylcarbonyigiycmamido" refers to a radical of the tormula -N(H)-C(0)-CH 2 -N. H)-C(OV R wnere R b is an aryl radical as defined above e g , pnenyicaroonylgiycinamido (4-fluoro-3- trιfluoromethyiphenyl)carbonylglycιπamιdo, (4-fluoropnenyl)carnonylglycinamido, and the like "(Arylcarbonyl)(alkyl)glycinamido" refers to a radical of the formula -N(H)-C(O)-CH 2 -N(R a )-C(O)-R b wnere R a is an alkyl radical as defined above and R b is an aryl radical as defined above and the nitrogen to which the R a radical is attached is designated as "ΛT, e.g., (phenylcarbonyl)(-V'-methyl)glycιnamιdo, ((4-fluoro-3- tπfiuoromethylphenyl)carbonyl)(/V'-ethyl)glycιnamιdo, ((4-fluorophenyi)caroonyl)(Λ/'-methyl)glycιnamιdo, and the like "Araikyl" refers to a radical of the formula -R a R b where R a is an alkyl radical as defined above and R b is an aryl radical as defined above, e.g., benzyl, and the like. "Aralkylcarbonyl" refers to a radical of the formula -C(O)-R d where R < j is an aralkyl radical as defined above, e.g., benzylcarbonyl, 1-(phenyl)ethylcarbonyl, and the like. "Aralkylcarbonylalkyl" refers to a radical of the formula -R a C(0)R d where R a is an alkyl radical as defined above and Rm, is an aralkyl radical as defined above, e.g., benzylcarbonylmethyl, 2-(1-(phenyl)ethylcarbonyl)ethyl, and the like. "Aralkenyl" refers to a radical of the formula -R c R where R b is an aryl radical as defined above and R c is an alkenyl radical as defined above, e.g., 3-phenyipropyiιd-1-enyl, and the like "Aryloxy" refers to a radical of the formula -OR b wnere R b is an aryl radical as defined above, e.g., phenoxy and naphtnoxy, and the like "Aralkoxycarbonyl" refers to a radical of the formula -C(0)OR d where _ is an aralkyl radical as defined above, e.g., benzyloxycarbonyl, and the like. "Aralkoxycarbonylalkyl" refers to a radical of the formula -R a C(0)OR d wnere R a is an alkyl radical as defined above and R η is an aralkyl radical as defined above, e.g., benzyloxycarbonylmethyl, 2-(benzyloxycarbonyl)ethyl, 3-((πaphthalen-2-yl)oxy)carbonyl)propyl, and the like. "Aryloxyalkyl" refers to a radical of the formula -R a -OR b wnere R a is an alkyl radical as defined above and R is an aryl radical as defined above e g , phenoxvmethyl 2-(phenoxy)ethyl, 3-(phenoxy)propyl, and the like "Aryloxyalkylcarbonyloxyalkyl" refers to a radical of the formula -R a -OC.O)-R a -OR b where each R a is independently an alkyl radical as defined above and R is an aryl radical as defined above, e.g., phenoxymethylcarbonyloxymethyl, (2-phenoxvethyl)caroonyloxymethyl 3-((2-phenoxyethyl)carbonyloxy)propyl, and the like. "Aralkoxy" refers to a radical of the formula -OR d where R d is an aralkyl radical as defined above, e.g., benzyloxy, and the like "Aralkoxylalkyl" refers to a radical of the formula -R^OR^ wnere R a is an alkyl radical as defined above and R_ is an aralkyl radical as defined above, e.g., benzyloxymethyl, 2-phenylethoxymethyl, and the like. "Aralkoxyalkylcarbonyloxyalkyl" refers to a radical of the formula -R a -OC(0)-R a -OR d where each R a is independently an alkyl radical as defined above and R d is an aralkyl radical as defined above, e.g., benzyloxymethylcarbonyloxymethyl, (2-(phenyl)ethoxymethyl)- carbonyloxymethyl, 2-((2-(phenyl)ethoxymethyl)carbonyloxy)ethyl, and the like. "Alkoxyalkyl" refers to a radical of the formula -R a OR a where each R a is independently an alkyl radical as defined above, e.g., methoxyethyl, ethoxymethyi, propoxymethyl, propoxyethyl, and the like. "Alaninamido" refers to a radical of the formula -N(H)-C(0)-C(CH 3 )H-NH 2 "Alanimamidoalkyl" refers to a radical of the formula -R a -N(H)-C(0)-C(CH 3 )H-NH 2 where R a is an alkyl radical as defined above, e.g., alaninamidomethyl, 2-(alanιnamιdo)ethyl, 1- (alanιnamιdo)ethyl, 3-(aianιnamιdo)propyl, and the like "Azidoaikyl" refers to radical of the tormula -R a -N 3 wnere R a is an alkyl radical as defined above, e.g., 2-azιdoethyl, 3-azιdopropyl, 2-azιdopropyl 4-azιdobutyl, and the like "Benzyl" refers to a radical of the formula -CH 2 -R h where R h is a phenyl radical optionally substituted by one or more substituents selected from the group consisting of hydroxy, halo, alkyl, haloalkyl, alkoxy, alkenyl, nitro, cyano, am o, monoalkylamino, dialkylamino, alkylcarbonyl, carboxy, alkoxycarbonyl, and aminocarbonyl "Benzyicaroonyl" refers to a radical of the formula -C(0)-CH 2 -R h where R h is a phenyl radical as defined above, e.g , (4-methoxybenzyl)caroonyl, (3-fluoroDenzyl)carbonyl, and the "Carboxy" refers to the radical -C(0)OH "Carboxyalkyl" refers to the radical of the tormula -R 3 -C(0)OH wnere R a is an alkyl radical as defined above, e.g., carboxymethyl, 2-carooxyethyl, 3-carooxypropyl, and the like "(Carboxyalkyl)amιnocaroonyl" refers to a radical of the formula -C(0)-N(H)-R a -C(0)OH where R a is an alkyl radical as defined above, e g , (carboxymethyl)amιnocarbonyl, (2- carboxyethyl)amιnocarbonyl, (l-carboxyethyl)amιnocarbonyl, and the like. "Carbocyciic πng system" refers to a stable 3- to 15-membered πng radical consisting solely of carbon and hydrogen atoms. For purposes of this invention, the caroocyclic ring system radical may be a monocyclic, bicyclic or tncyclic ring system, and may include fused or bndged ring systems, and the ring system may be partially or fully saturated or aromatic, and the caroon atoms in the ring system may be optionally oxidized Examples of such caroocyclic ring system radicals include, but are not limited to, cyclopropyl, cyclobutyl, cyclohexyl, norbornane, norbornene, adamantyl, bιcyclo[2.2.2]octane, phenyl, naphthyl, indenyl, azulenyl, fluorenyl, anthracenyl, and the like. "Cycloalkyl" refers to a stable 3- to 10-membered monocyclic or bicyclic radical which is saturated, and which consist solely of carbon and hydrogen atoms, e.g., cyclopropyl, cyclobutyl, cyclobutyl, cyclohexyl, decalmyl and the like. Unless otherwise stated specifically in the specification, the term "cycloalkyl" is meant to include cycloalkyl radicals which are optionally substituted by one or more substituents independently selected from the group consisting of alkyl, halo, hydroxy, ammo, nitro, alkoxy, carboxy, phenyl and alkoxycarbonyl. "Cycloalkylalkyl" refers to a radical of the formula -R a -R e wnere R a is an alkyl radical as defined above and Rg is a cycloalkvl radical as defined above, e g., cyclopropylmethyl, 2-cyclobutylethyl, 3-cyclohexylpropyl, and the like "Cycloalkylamino" refers to a radical of the formula -N(H)-R € wnere R e is a cycloalkyl radical as defined above, e.g , cyclopropylamino, cyclobutylammo, cyclohexylarπino, and the like "Cycloalkyiaminoalkyl" refers to a radical of the formula -R a -N(H)-R e where R a is an alkyl radical as defined above and R e is a cycloalkyl radical as defined above, e.g , cyclopropylaminomethyl, 2-(cyclobutylamιno)ethyl, cyclohexylammomethyl, and the like "(Cycloalkylalkyl)amιno" refers to a radical of the formula -N(H)-R a -R e where R a is an alkvl radical as defined above and Re is a cycloalkyl radical as defined above, e.g , (cyclopropylmethyl)amιno, (2-cvclobutylethyl)amιno, (3-cyclohexyιpropyl)amιno, and the like "(Cycloalkylalkyl)amιnoalkyl" refers to a radical of the formula -R a -N(H)-R a -R e where each R a is independently an alkyl radical as defined above and R e is a cycloalkyl radical as defined above, e.g., (cyciopropylrπethyl)amιnomethyl, 2-((2-cyclobutylethyl)amιno)ethyl, (3-cyclohexyipropyl)amιnomethyl, and the like "Cycloalkylcarbonyiammo" refers to a radical of the formula -C(0)-N(H)-R e wnere R e is a cycloalkyl radical as defined above, e.g., cyciopropylcarbonylamino, (2-phenylcyclopropyl)carbonyiamιno, cyclohexylcarbonytamino, 4-cyanodecalιnylcarbonylamιno cyclopentylcarbonylamino, and the like. "Cyctoalkylcarbonylaminoalkyl" refers to a radical of the formula -R a -C(0)-N(H)-Re where R a is an alkyl radical as defined above and Re is a cycloalkyl radical as defined above e.g., cyclopropytcarbonylaminomethyl, 2-((2-phenylcyctopropyi)carbonylamιno)ethyl, 1-(cyclohexytcarbonyiamιno)ethyl, (3-phenylcyclopentyl)carbonylamιnomethyl, and the like. "Cycloalkylalkylcarbonylamino" refers to a radical of the formula -C(0)-N(H)-R a -R e where R a is an alkyl radical as defined above and R e is a cycloalkyl radical as defined above, e.g., (cyclopropylmethyl)carbonylamιno, ((2-phenylcyclopropyl)methyl)carbonyiamιno, (2- cyclohexylethyl)carbonyiamιno, (l-cyclohexylethyl)carbonylamιno, and the like. "Cyano" refers to the radical -CN. "Cyanoalkyl" refers to a radical of the formula -R a CN where R a is an alkyl radical as defined above, cyanomethyl, 2-(cyano)ethyl, 3-(cyano)propyl, and the like. "DMF" refers to Λ.,/V-dιmethylformamιde. "DMSO" refers to dimethyisulfoxide. "Dialkylamino" refers to a radical of the formula -N(R a )R a where each R a is independently an alkyl radical as defined above, e.g., dimethytamino, methylethylammo, diethytammo, dipropylam o, ethylpropylamino, and the like. "Dialkylammoalkyl" refers to a radical of the formula -R a -N(R a )R a where each R a is independently an alkyl radical as defined above, e.g., dimethylamiπomethyl, methyethylamiπomethyl, 2-diethylamιnoethyl, 3-dιpropylamιnopropyl, and the like. "Dialkylaminocarbonyl" refers to a radical of the formula -C(0)N(R a )R a where each R a is independently an alkyl radical as defined above, e g., dimethyiaminocarDonyl, methylethylammocaroonyl, diethytammocaroonyl, dipropylammocarbonyl, ethylpropylaminocarbonyl, and the like. "Dialkylaminocarbonylalkyl" refers to a radical of the formula -R a -C(0)N(R a )R a where each R a is independently an alkyl radical as defined above, e.g., dimethylammocarbonylmethyl, 2-(methyiethylamιnocarbonyl)ethyl, 3-(dιethylamιnocarbonyl)propyl, 2-(dιpropylamιπocaroonyl)propyl, and the like. "Dialkylaminocarbonyloxyalkyl" refers to a radical of the formula -R a -0-C(0)-N(R a )R a where each R a is independently an alkyl radical as defined above, e.g, dimethylaminocarbonyloxymethyl, 2-(methylethylamιπocarbonyloxy)ethyl, 3- (diethylamιnocarbonyloxy)propyl, 2-(dipropylamιnocarbonyloxy)propyl, and the like. "Dialkylureido" refers to a radical of the formula -N(H)-C(O)-N(R a )(R a ) or a radical of the formula -N(R a )-C(O)-N(R a )H where each R a is independently an alkyl radical as defined above and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g., N', Λ/'-dι(methyl)ureιdo, Λ/'-methyl-Λ/'-ethylurβido, Λ ',Λ/'-dι(ethyl)ureιdo, N',N'- dι(propyl)ureιdo, Λ/-methyl-Λ/'-ethylureιdo, and the like. "Diarylureido" refers to a radical of the formula -N(H)-C(O)-N(R b )(R b ) or a radical of the formula -N(R b )-C(0)-N(R b )H where each R b is independently an aryl radical as defined above and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g., Λ/',/V'-dι(phenyl)ureιdo, Λ/'-phenyl-Λ/-(3-nιtro)phenylureιdo, ΛT.Λf -dι(4- methoxyphenyl)ureιdo, Λ/',Λ/'-dι(4-chloropnenyl)ureιdo ^-chlorophenyl-/V'-(3- ch!oropnenyl)ureιdo and the like "Dialkylureidoalkyl" refers to a radical of the tormula -R a -N(H)-C(0)-N(R a )(R a ) or a radical of the formula -R a -N(R a )-C(0)-N(R a )H where each R a is independently an alkyl radical as defined above and the attached nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g., /V',/V'-di(methyl)ureioomethyl, 2-(Λ/'-methyl-Λ/'-ethylureιdo)ethyl, 1- (Λ/',/V'-dι(ethyl)ureιdo)ethyl, 3-(Λ/',Λ/'-dι(propyl)ureιdo)propyl, 2-(Λ/-methyl-Λ/'-ethylureιdo)ethyl, "Formyl" refers to the radical -C(O)H "Formylalkyl" refers to a radical -R 3 -C(0)H wnere R 3 is an alkyl radical as defined above, e.g., formylmethyl, 2-(formyl)ethyl, 3-(formyl)propyι and the like "Glycmamido" refers to a radical of the formula -N(H)-C(0)-CH 2 -NH 2 "Glycinamidoalkyl" refers to a radical of the formula -R a -N(H)-C(0)-CH 2 -NH 2 wnere R a is an alkyl radical as defined above, e.g., glycinamidomethyl, 2-(glycιnamιdo)ethyl, 1- (glycιnamιdo)ethyl, 3-(glycιnamιdo)propyl, and the like "Guanidino" refers to the radical -N(H)-C(NH)-NH 2 "Halo" refers to bromo, chioro, lodo or fluoro "Haloalkyl" refers to an alkyl radical, as defined above, that is substituted by one or more halo radicals, as defined above, e.g., tπfluoromethyl, difiuorometnyl, tπchloromethyl, 2-tπfluoroethyl, 1 -fluoromethyl-2-fluoroethyl, 3-bromo-2-fluoropropyl, 1-bromomethyl-2-bromoethyl, and the like "Haloalkoxy" refers to a radical of the formula -OR f wnere R f is an haloalkyl radical as defined above, e.g., tπfluoromethoxy, difluoromethoxy, tπchloromethoxy, 2,2,2-trιfluoroethoxy, 1-fluoromethyl-2-fluoroethoxy, 3-bromo-2-fluoropropoxy, 1-bromomethyl-2-bromoethoxy, and the like. "Haloalkylcarbonylamino" refers to a radical of the formula -N(H)-C(O)-R. where R f is an haloalkyl radical as defined above, e.g., trifluoromethylcarbonylamino, trifluoromethylcarbonylamino, 2-bromoethylcarbonylamιno, and the like. "(Haloalkylcarbonyi)ureιdo" refers to a radical of the formula -N(H)-C(0)-N(H)-C(0)-R f where R f is a haloalkyl radical as defined above, e.g., (tπchloromethylcarbonyl)ureιdo, (3- fluoropropylcarbonyl)ureιdo, and the like. "(Haloaikyl)(alkyl)ureιdoalkyl" refers to a radical of the formula -R a -N(R a )-C(0)-N(H)-R f or a a radical of the formula -R a -N(R f )-C(0)-N(H)-R a or a radical of the formula -R a -N(H)-C(0)- N(R a )R f where each R a is independently an alkyl radical as defined above and R f is an haloalkyl radical as defined above and terminal nitrogen is designated as "N" and the other nitrogen is designated as "AT', e.g., /V'-(2-chloroethyl)-Λ/-(methyl)ureιdomethyl, and 2-(Λ/'-(2- chloroethyl)-Λ/-(methyl)ureido)ethyl, and the like. "Haloalkylcarbonylammoalkyl" refers to a radical of the formula -R a -N(H)-C(0)-R f where R a is an alkyl radical as defined above and R f is an haloalkyl radical as defined above, e.g., tπfluoromethyicarbonylaminomethyl, 2-(tπfluoromethvlcaroonylamιno)ethyl, and the like "Hydroxy" refers to the radical -OH "Hydroxyalkyl" refers to a alkyl radical as defined above that is substituted by a hydroxy radical, e.g., hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 4-hydroxybutyl, 3-hydroxybutyl, and the like. "(Hydroxyalkyl)amιnocarbonyl" refers to a radical of the formula -C(0)-N(H)-R a -OH where R a is an alkyl radical as defined above, e.g., hydroxymethytaminocarbonyl, (2-hydroxyethyl)amιnocarbonyl, (l-hydroxyethyl)amιnocarbonyl, and the like. "Hydroxyalkoxy" refers to a radical of the formula -OR a -OH where R a is an alkyl radical as defined above, e.g., 2-hydroxyethoxy, 2-hydroxypropoxy, 4-hydroxybutoxy, 3-hydroxybutoxy, and the like. "(Hydroxyalkoxy)carbonyl" refers to a radical of the formula -C(O)-OR a -OH where R a is an alkyl radical as defined above, e.g., (2-hydroxyethoxy)carbonyl, (2-hydroxypropoxy)carbonyl, (4-hydroxybutoxy)carbonyl, (3-hydroxybutoxy)carbonyl, and the like. "(Hydroxy)aralkyP' refers to an aralkyl radical as defined above wherein the alkyl radical therein is substituted by a hydroxy radical, e.g., (phenyl)(hydroxy)methyl, 2-phenyl-1- hydroxyethyl, 2-phenyl-3-hydroxypropyl, and the like. "(Hydroxyalkylthιo)alkyl" refers to an alkylthioalkyl radical as defined above that is substituted by an hydroxy radical, e.g., 2-hydroxyethylthιomethyl, 2-(hydroxymethylthιo)ethyl, and the like. "Hydroxyalkenyl" refers to an alkenyl radical as defined above that is substituted by a hydroxy radical, e g., 3-hydroxyprop-1-enyl, 4-hydroxybut-1-enyl, 4-hydroxypent-1-enyl, 5-hydroxypenta-1 ,3-dιenyl, and the like "Hydroxyalkynyl" refers to an alkynyl radical as defined above that is substituted by a hydroxy radical, e g., 3-hydroxyprop-ynyl, 4-hydroxypent-2-ynyl, 1-hydroxybut-3-ynyl, and the "(Hydroxy)cycloalkylalkyl" refers to a radical of the formula -R a (OH)-R e where R a is an alkyl radical as defined above and R e is a cycloalkyl radical as defined above and where the OH radical is a substituent on any carbon of the R a radical, e g , 2-cyclopropyl-1-hydroxyethyl, (4-hydroxycyc!ohexyl)methyl, and the like "Hydroxyalkylammoalkyl" refers to a monoalkylaminoalkyl radical as defined below that is substituted by a hydroxy radical, e.g., 2-hydroxyethylamιnomethyl, 2-(3- hydroxypropylamιno)ethyi, and the like "Hydroxyamidino" refers to a radical of the formula -C(NH 2 )=NOH "Heterocyclic ring system" refers to a stable 3- to 15-membered ring radical which consists of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur For purposes of this invention, the heterocyclic ring system radical may be a monocyclic, bicyclic or tncyclic ring system, which may include fused or bπdged ring systems; and the nitrogen, carbon or sulfur atoms in the heterocyclic ring system radical may be optionally oxidized; the nitrogen atom may be optionally quaternized; and the heterocyclic ring system may be partially or fully saturated or aromatic The heterocyclic ring system may be attached to the main structure at any heteroatom or carbon atom which results in the creation of a stable compound Examples of such heterocyclic radicals include, but are not limited to, azepinyl, acπdinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl, carbazolyl, cinnohnyl, decahydroisoquinolyl, dioxolanyl, furanyl, isothiazolyl, qumuclidinyl, imidazolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, indolyl, isomdolyl, indolmyl, isoindo nyl, indanyl, indolizmyl, isoxazolyl, isoxazolidinyl, morpholmyl, naphthyπdinyl, oxadiazolyl, octahydromdolyl, octahydroisoindolyl, 2-oxopιperazιnyl, 2-oxopιpeπdιnyl, 2-oxopyrrolιdιnyl, 2-oxoazepιnyl, oxazolyl, oxazolidmyl, pipeπdinyl, piperazmyl, 4-pιpeπdonyl, phenazinyl, phenothiazinyl, phenoxazmyl, phthalazinyl, ptendinyl, puπnyl, pyrrolyl, pyrro dinyl, pyrazolyl, pyrazolidmyl pyπdinyl, pyrazinyl, pyπmidinyl, pyπdazinyl, quinazolmyl, quinoxalmyl, quinolinyl, qumuclidinyl isoquinoiinyl, thiazolyl, thiazolidmyl, thiadiazolyi, tπazolyl, tetrazolyl, tetrahydrofuryl, tπazinyl tetrahydropyranyl, thienyl, thiamorpholmyl, thiamorphol yl sulfoxide, and thiamorpholinyl sulfone "Heterocyclyl" refers to a heterocyclic ring system as defined above Unless stated otherwise specifically in the specification, the term "heterocyclyl" is meant to include a heterocyclic ring system as defined above which is optionally substituted by one or more substituents selected from the group consisting of hydroxy, mercapto, halo, alkyl, alkenyl alkynyl phenyl, phenylalkyl, phenylalkenyl, alkoxy, phenoxy, phenylalkoxy, haloalkyl, haloalkoxy, formyl, nitro, cyano, amidmo, cycloalkyl hydroxyalkyl, alkoxyalkyl, phenoxyalky phenylalkoxyalkyl, ammo, monoalkylamino, dialkylamino, monophenylamino, monophenylalkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monophenyiaminoaikyl, monophenylalkylaminoalkyl, carboxy, alkoxycarbonyl, phenylcarbonyl benzylcarbonyl, alkylcarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, phenylaminocarbonyl, ammocarbonylalkyl monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, ureido, monoalkylureido, monophenylureido, monobenzylureido, as defined herein "Heterocyclylalkyl" refers to a radical of the formula -R a R g where R a is an alkyl radical as defined above and R g is a heterocyclyl radical as defined above, e g , indolinylmethyl or imidazolylmethyl, and the like "Heterocyclylamino" refers to a radical of the formula -N(H)-R g where R g is a heterocyclyl radical as defined above, e.g., oxazol-2-ylamιno; pιpeπdιn-4-ylamιno, and the like "Heterocyclylaminoalkyl" refers to a radical of the formula -R a -N(H)-R g where R a is an alkyl radical as defined above and R g is a heterocyclyl radical as defined above, e.g., oxazol-2- ylaminomethyl, 2-(oxazol-2-ylamιno)ethyl, pιperidιn-4-ylamιnomethyl, 2-(pιpeπdιn-4- ylamιno)ethyl, and the like. "Heterocyclylcarbonylamino" refers to a radical of the formula -N(H)-C(0)-R g where R g is a heterocyclyl radical as defined above, e.g., pιpeπdιn-4-ylcarbonylamιno, furan-2- ylcarbonylammo, morphotιn-4-ylcarbonylamιno, and the like. "Heterocyclylcarbonylammoalkyl" refers to a radical of the formula -R a -N(H)-C(0)-R g where R a is an alkyl radical as defined above and R g is a heterocyclyl radical as defined above, e.g., pιperιdιn-4-ylcarbonylamιnomethyl, 2-(furan-2-yicarbonylamιno)ethyl, 1 -(morpholιn-4- ytcarbonylamιno)ethyl, and the like. "Mercapto" refers to the radical -SH. "Mercaptoalkyl" refers to a radical of the formula -R a -SH where R a is an alkyl radical as defined above, e.g., mercaptomethyl, 2-mercaptoethyl, 3-mercaptopropyl, 2-mercaptobutyl and the like. "Monoalkylamino" refers to a radical of the formula -N(H)R a where R a is an alkyl radical as defined above, e.g., methylamino, ethylamino, propylamiπo, and the like "Monoalkylaminoalkyl" refers to a radical of the formula -R a -N(H)R a where each R a is independently an alkyl radical as defined above, e.g., methylammomethyl, ethylaminomethyl, 2-(propylamιno)ethyl, and the like. "(Monoalkyiamino)aralkyl" refers to a radical of the formula -R -N(H)R a where R a is an alkyl radical a defined above and R < j is an aralkyl radical as defined above, e.g., (methylamιno)(phenyl)methyl, 1-(ethylamιno)-1-(4-methoxyphenyl)ethyl, 2-(isopropyiammo)-3- (3-chlorophenyl)propyl, and the like. "Monoarylamino" refers to a radical of the formula -N(H)R wnere R b is an aryl radical as defined above, e.g., phenylamino, (4-methoxyphenyl)amιno, (3,4,5-trιmethoxyphenyl)amιno and the like. "Monoarylaminoalkyl" refers to a radical fo the formula -R a -N(H)R b where R a is an alkyl radical as defined above and R is an aryl radical as defined above, e.g., phenylaminomethyl, 2-((4-methoxyphenyl)amιno)ethyl, 3-((3,4,5-tπmethoxyphenyl)amιno)propyl, and the like. "Monoaralkylamino" refers to a radical of the formula -N(H)R where R d is an aralkyl radical as defined above, e.g., benzylammo, (3,4,5-trιmethoxybenzyl)amιno, (4-chlorobenzyl)amιno,and the like. "Monoaralkylaminoalkyl" refers to a radical of the formula -R a -N(H)R d where R a is an alkyl radical as defined above and R d is an aralkyl radical as defined above, e.g., benzylaminomethyl, (3-phenylpropyl)amιnomethyl, 2-(benzylamιno)ethyl, and the like "Monoalkylammocaroonyl" refers to a radical of the formula -C(O)N(H)R a where R a is an alkyl radical as defined above, e.g , methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyt, and the like. "Monoalkylaminocarbonylalkyl" refers to a radical of the formula -R a -C(0)N(H)R a where each R a is independently an alkyl radical as defined above, e g , methylaminocarbonylmethyl, 2-(ethylamιnocarbonyl)ethyl, 3-(propylamιnocarbonyl)propyl, and the like "Monoarylaminocarbonyl" refers to a radical of the formula -C(0)N(H)R b where R b is an aryl radical as defined above, e.g., phenylaminocarbonyl, (3,4,5-fπs(tπfluoromethoxy)phenyl)- ammocarbonyl, (4-chlorophenyl)amιnocarbonyl, and the like "Monoarylammocarbonylalkyl" refers to a radical of the formula -R a -C(0)N(H)R b where R a is an alkyl radical as defined above and R b is an aryl radical as defined above, e g , phenylaminocarbonylmethyl, 2-((4-chlorophenyl)amιnocarbonyl)ethyl, 3-((3,4,5- tπmethoxyphenyl)amιnocarbonyi)propyl, and the like "Monoaralkylaminocarbonyl" refers to a radical of the formula -C(0)N(H)R where R d is an aralkyl radical as defined above, e.g., benzylaminocarbonyl, (3,4,5-fπs(trifluoromethoxy)benzyl)-amιnocarbonyl, (4-chlorobenzyl)amιnocarbonyl, and the like "Monoaralkylaminocarbonyialkyl" refers to a radical of the formula -R a -C(0)N(H)R d where R a is an alkyl radical as defined above and (^ is an aralkyl radical as defined above, e g , benzylaminocarbonylmethyl, 2-((4-chlorobenzyl)amιnocarbonyl)ethyl, 3-((3,4,5- trιmethoxybenzyl)amιnocarbonyl)propyl, and the like "(Monoalkytamιnocarbonylalkyi)amιnocarbonyl" refers to a radical of the formula -C(0)-N(H)-R a -C(O)-N(H)R a where each R a is independently an alkyl radical as defined above, e g , (methylamιnocarbonylmethyl)amιnocarbonyl, (2-(methylamιnocarbonyl)ethyl)amιnocarbonyl, (1-(ethylamιnocarbonyl)ethyl)amιnocarbonyl "Monoalkylalaninamido" refers to radical of the formula -N(H)-C(O)-C(CH 3 )H-N(H)R a where R a is an alkyl radical as defined above and the attached nitrogen is designated as "N" and the other nitrogen (having the R a substituent) is designated as "N", e g , N'- methylalanimido, Λ/'-ethylalanιmιdo, and the like "Monoalkylglycinamido" refers to a radical of the formula -N(H)-C(0)-CH 2 -N(H)R a where R a is an alkyl radical as defined above and the attaching nitrogen is designated as "N" and the other nitrogen (having the R a substituent) is designated as "N", e g , Λ/'-methylglycmamido N'- ethylglycinamido, and the like "(Monoarylamιnocarbonyl)glycιnamιdo" refers to a radical of the formula -N(H)-C(0)-CH 2 -N(H)-C(0)-N(H)R b where R b is an aryl radical as defined above, e g , ((4- phenoxyphenyl)amιnocarbonyl)glycιnamιdo, ((4-chlorophenyl)amιnocarbonyl)glycιnamιdo, (phenylamιnocarbonyl)glycιnamιdo, and the like "(Monoarylamιnocarbonyl)(alkyl)glycιnamιdo" refers to a radical of the formula -N(H)-C(0)-CH 2 -N(R a )-C(0)-N(H)R b where R a is an alkyl radical as defined above and R b is an aryl radical as defined above and the nitrogen to which R a is attached is designated as "N" e g , ((4-phenoxyphenyi)amιπocarbonyl)(Λ/'-methyl)glycιnamιdo, ((4-chiorophenyl)amιnocarbonyl)(Λ/'-ethyl)glycιnamιdo (phenylamιnocarbonyl)(Λ. '-methyl)glycιnamιdo, and the like "(Monoaralkylamιnocarbonyl)glycιnamιdo" refers to a radical of the formula -N(H)-C(O)-CH 2 -N(H)-C(O)-N(H)R d where R d is an aralkyl radical as defined above, e g , ((4- phenoxybenzyl)amιnocarbonyl)glycιnamιdo, ((4-chlorobenzyl)amιnocarbonyl)glycιnamιdo (benzylamιnocarbonyl)glycιnamιdo, and the like "(Monoaralkylamιnocarbonyl)(alkyl)glycιnamιdo" refers to a radical of the formula -N(H)-C(O)-CH 2 -N(R a )-C(O)-N(H)R d where R a is an alkyl radical as defined above and R d is an aralkyl radical as defined above and the nitrogen to which the R a is attached is designated as "N", e g , ((4-phenoxybenzyl)amιnocarbonyl)(/V'-methyl)glycιnamιdo, ((4-chlorobenzyl)amιnocarbonyl)(Λ/'-ethyl)glycιnamιdo, (benzyiamιnocarbonyl)(/V-methyl)glycιnamιdo, and the like. "Monoalkylureido" refers to a radical of the formula -N(H)-C(0)-N(H)R a or a radical of the formula -N(R a )-C(O)-NH 2 where R a is an alkyl radical as defined above and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g., Λ/'-methylureιdo, Λ/'-ethylureιdo, Λf-propylureido, Λ/-methylureιdo, Λ/-ethylureιdo, Λ/-propylureιdo, and the like "Monophenyiureido" refers to a radical of the formula -N(H)-C(O)-N(H)R h where R h is a phenyl radical as defined above, and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e g , Λ/'-phenyiureido, W-(4-nitrophenyl)ureido, Λ/'-(3- chlorophenyl)ureιdo, and the like "Monobenzylureido" refers to a radical of the formula -N(H)-C(0)-N(H)-CH 2 -R h wnere R h is a phenyl radical as defined above, and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g., Λf-benzylureido, Λ/-(4-nιtrobenzyl)ureιdo, Λ/'-(3- chlorobenzyl)ureιdo, and the like. "Monohaloalkylureido" refers to a radical of the formula -N(H)-C(0)-N(H)R f or a radical of the formula -N(R f )-C(O)-NH 2 where R f is a haloalkyl radical as defined above and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g., N'- chloromethylureido, Λf-(2,2-dιfluoroethyl)ureιdo, Λ/'-(3-chloropropyl)ureιdo, N- (tπfluoromethyl)ureιdo, Λ/-(pentafluoroethyl)ureιdo, /V-(3-ιodopropyl)ureιdo, and the like "Monoarylureido" refers to a radical of the formula -N(H)-C(0)-N(H)R b or a radical of the formula -N(R b )-C(0)-NH 2 where R is an aryl radical as defined above and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g , Λ/-phenylureιdo, Λ/'-(4-methoxyphenyl)ureιdo, Λf-(3-chlorophenyl)ureιdo, Λ/-phenylureιdo, Λ/-(2- tπfluoromethylphenyl)ureιdo, Λ/-(4-chlorophenyl)ureιdo, and the like "Monoaralkylureido" refers to a radical of the formula -N(H)-C(0)-N(H)R d or a radical of the formula -N(R d )-C(O)-NH 2 where R < j is an aralkyl radical as defined above and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g., Λ/'-benzylureido, Λf-(4-methoxybenzyl)ureιdo, Λ/-(3-chlorobenzyl)ureιdo, Λ/-benzylureιdo, N-(2- tπfluoromethylbenzyl)ureιdo, Λ/-(4-chlorobenzyl)ureιdo, and the like. "(Monoalkyl)(monoaryl)ureιdo" refers to a radical of the formula -N(R a )-C(0)-N(R b )H, or a radical of the formula -N(R b )-C(O)-N(R a )H, or a radical of the formula -N(H)-C(0)-N(R a )(R b ) where R a is an alkyl radical as defined above and R is an aryl radical as defined above, and where the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g , /V-methyl-Λ/'-phenylureιdo, /V-phenyl-Λ/'-ethylureιdo, /V-methyl-Λ/-(4-fluorophenyl)ureιdo, N'- ethyl-/v"-(3-cyanophenyl)ureιdo, and the like. "Monoalkylureidoalkyl" refers to a radical of the formula -R a -N(H)-C(O)-N(H)R a or a radical of the formula -R a -N(R a )-C(0)-NH 2 where R a is an alkyl radical as defined above and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e g , N'- methylureidomethyi, 2-(Λ/'-ethylureιdo)ethyl, 1-(/V'-propylureιdo)ethyl, Λ/-methylureιdomethyl 2-(Λ/-ethylureιdo)ethyl, 1-(Λ/-propylureιdo)ethyl, and the like "Monohaloalkylureidoalkyl" refers to a radical of the formula -R a -N(H)-C(0)-N(H)R, or a radical of the formula -R a -N(R f )-C(0)-NH 2 where R a is an alkyl radical as defined above and R f is a haloalkyl radical as defined above and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g , Λ/'-chloromethylureidomethyl, 2- (Λ/-(2,2-dιfluoroethyl)ureιdo)ethyl, 1-(Λ/'-(3-chloropropyl)ureιdo)ethyl, /V-(tπfluoromethyl)ureιdomethyI, 2-(/V-(pentafluoroethyl)ureιdo)ethyl, 1 -(Λ/-(3- ιodopropyl)ureιdo)ethyl, and the like "Monoarylureidoalkyl" refers to a radical of the formula -R a -N(H)-C(O)-N(H)R b or a radical of the formula -R a -N(R b )-C(0)-NH 2 where R a is an alkyl radical as defined above and R b is an aryl radical as defined above and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g , Λ/'-phenylureidomethyl, 2-(Λf-(4- methoxyphenyl)ureιdo)ethyl, 1-(Λ '-(3-chlorophenyl)ureιdo)ethyl, Λ/-phenylureιdomethyl, 2-(Λ/-(2- tπfluoromethylphenyl)ureιdo)ethyl, 1-(/V-(4-chlorophenyl)ureido)ethyl, and the like "Monoaralkylureidoalkyl" refers to a radical of the formula -R a -N(H)-C(0)-N(H)R d or a radical of the formula -R a -N(R d )-C(O)-NH 2 where R a is an alkyl radical as defined above and R is an aralkyl radical as defined above and the attaching nitrogen is designated as "N" and the other nitrogen is designated as "N", e.g., Λ/'-benzylureιdomethyl, 2-(Λ/'-(4- methoxybenzyi)ureιdo)ethyl, 1 -(Λ/'-(3-chiorobenzyl)ureιdo)ethyl, Λ/-benzylureιdomethyl, 2-(Λ/-(2-tπfluoromethylbenzyl)ureιdo)ethyl, 1-(Λ/-(4-chlorobenzyl)ureιdo)ethyl, and the like "Monophenylamino" refers to an ammo radical substituted by a phenyl radical as defined herein "Monophenylalkylamino" refers to an ammo radical substituted by a phenylalkyl group as defined below, e.g., benzylamino, 2-(benzyl)butylamιno, and the like. "Monophenylaminoalkyl" refers to an alkyl radical as defined above substituted by a monophenylamino group as defined above, e g., (phenylamιno)methyl, 2-(1- (phenyl)ethylamιno)ethyl, and the like "Monophenylalkylammoalkyl" refers to an alkyl radical as defined above substituted by a monophenylalkylamino group as defined above, e g , (benzylamιno)methyl, 2-(2- benzyl)butylamιno)ethyl, and the like. "Nitro" refers to the radical -NO 2 "Oxo" refers to the subsituent =O. "Optional" or "optionally" means that the subsequently described event of circumstances may or may not occur, and that the description includes instances where said event or circumstance occurs and instances in which it does not For example, "optionally substituted aryl" means that the aryl radical may or may not be substituted and that the description includes both substituted aryl radicals and aryl radicals having no substitution "Phenyl" refers to the benzene radical optionally substituted by one or more substituents selected from the group consisting of hydroxy, halo, alkyl, haloalkyl, alkoxy, alkenyl, nitro, cyano, ammo, monoalkylamino, dialkylammo, alkylcarbonyl, carboxy, alkoxycarbonyl, and aminocarbonyl "Phenoxy" refers to the radical of the formula -OR h where R h is phenyl as defined above "Phenylalkyl" refers to an alkyl radical as defined above substituted by a phenyl radical, e.g , benzyl, and the like. "Phenylalkenyl" refers to an alkenyl radical as defined above substituted by a phenyl radical, e.g., 3-phenylprop-2-enyl, and the like "Phenylalkoxy" refers to a radical of the formula -OR, where R, is a phenylalkyl radical as defined above, e.g., benzyloxy, and the like "Phenylalkoxyalkyl" refers to an alkyl radical as defined above substituted by a phenylalkoxy radical as defined above, e g , benzyloxymethyl, and the like "Phenylcarbonyl" refers to a radical of the formula -C(O)-R h where R h is a phenyl radical as defined above, e.g., (4-chlorophenyl)carbonyl, (4-fluorophenyl)carbonyl, and the like "Phenylaminocarbonyl" refers to a radical of the formula -C(O)-N(H)-R h where R h is a phenyl radical as defined above, e.g , (4-chlorophenyl)amιnocarbonyl, (4- methoxyphenyi)amιnocarbonyl, and the like. "Pharmaceutically acceptable counteπon" " refers to those anions which retain the biological effectiveness and properties of the parent compound which are not biologically or otherwise undesirable Examples of such anions may be found in Berge, S M ef al , Journal of Pharmaceutical Sciences (1977), Vol 66, No 1 , pp 1-19 "Pharmaceutically acceptable salt" includes both acid and base addition salts "Pharmaceutically acceptable acid addition salt" refers to those salts which retain the biological effectiveness and properties of the free bases, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuπc acid, nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, pyruvic acid, maleic acid, malonic acid, succmic acid, fumaπc acid, tartaπc acid, citric acid, benzoic acid, mandeiic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like "Pharmaceutically acceptable base addition salt" refers to those salts which retain the biological effectiveness and properties of the free acids, which are not biologically or otherwise undesirable These salts are prepared from addition of an inorganic base or an organic base to the free acid Salts derived from inorganic bases include, but are not limited to, the sodium potassium, lithium, ammonium, calcium, magnesium, zinc, aluminum salts and the like Preferred inorganic salts are the ammonium, sodium, potassium, calcium, and magnesium salts Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, tπmethylamine, diethylamine, tπethylamine, tπpropylamine, ethanolamine, 2-dιmethylamιnoethanol, 2-dιethytamιnoethanol, tπmethamine, dicyciohexylamine, lysme, arginme, histidme, caffeine procaine, hydrabamine, choline, betame, ethylenediamme, glucosamine, methylglucamine, theobromme, puπnes, piperazine, pipeπdine, tV-ethylpιperιdιne, polyam e resins and the like Particularly preferred organic bases are isopropylamine, diethylamine, ethanolamine, tnmethylamine, dicyclohexylamine, choline and caffeine. "THF" refers to tetrahydrofuran. "Therapeutically effective amount" refers to that amount of a compound of formula (I) which, when administered to a human in need of such administration, is sufficient to effect treatment, as defined below, for inflammatory disorders which are alleviated by the inhibition of the activity of the chemokines, MIP-1 α and RANTES, in particular, for inflammatory disorders characterized by migration, accumulation and activation of leukocytes to the affected tissue The amount of a compound of formula (I) which constitutes a "therapeutically effective amount" will vary depending on the compound, the disorder and its severity, and the age of the human to be treated, but can be determined routinely by one of ordinary skill in the art having regard to his own knowledge and to this disclosure "Treating" or "treatment" as used herein cover the treatment of an inflammatory disorder in a human; and include: (i) preventing the disorder from occurring in a human, in particular, when such human is predisposed to the disorder but has not yet been diagnosed as having it, (ii) inhibiting the disorder, i.e., arresting its development; or (in) relieving the disorder, i.e., causing regression of the disorder "Ureido" refers to a radical of the formula -N(H)-C(0)-NH 2 "Ureidoalkyl" refers to a radical of the formula -R a -N(H)C(0)NH 2 where R a is an alkyl radical as defined above, e.g., ureidomethyl, 2-(ureιdo)ethyl, 3-(ureιdo)propyl, and the like It is understood from the above definitions and examples that for radicals containing a substituted alkyl group any substitution thereon can occur on any carbon of the alkyl group The compounds of the invention, or their pharmaceutically acceptable salts, may have asymmetric carbon atoms in their structure The compounds of the invention and their pharmaceutically acceptable salts may therefore exist as single stereoisomers, racemates, and as mixtures of enantiomers and diastereomers. All such single stereoisomers, racemates and mixtures thereof are intended to be within the scope of this invention. Absolute configuration of certain carbon atoms within the compounds, if known, are indicated by the appropriate absolute descriptor R OT S The descriptor "trans" is used to indicate that the R 1a or the R 1b substituents are on opposite sides of the piperazine plane The descriptor "cis" is used to indicate that the R 1a or the R 1 substituents are on the same side of the piperazine plane The nomenclature used herein is a modified form of the I U P A C system wherein the compounds of the invention are named as piperazine derivatives For example, a compound of formula (la) wherein R 6 is -C(O)-, R 5 is ethylene, R 4 is -0-, R 1a is in the 2-posιtιon of the piperazine ring and is ethoxycarbonyl, R 2 is 2-(ethyiamιno)ethyl in the 4-posιtιon of the phenyl ring and R 3 is naphthalen-1-yl substituted at the 4-posιtιon by methoxy, / e , the compound of the following formula is named herein as 1-(2-((4-methoxynaphthalen-1 -yl)oxy)ethyl)carboπyl-2-ethoxycarbonyl-4-(4- (2-(ethylamιno)ethyl)benzyi)pιperazιne Utility and Administration A. Utility The compounds of the invention inhibit the activity of the chemokines MIP-1α and RANTES and are therefore useful as anti- infiammatory agents In particular, the compounds are useful in treating inflammatory disorders such as multiple sclerosis, leukoencephalopathy, encephalomyelitis, Alzheimer's disease, Guiliian-Barre syndrome, acute cell-mediated renal transplant rejection, allograft rejection, rheumatoid arthritis, atherosclerosis, uπcaria, angioderma, allergic conjunctivitis, atopic dermatitis, allergic contact dermatitis, drug or insect sting allergy or systemic anaphytaxis Of particular interest to the invention is the use of the compounds to treat multiple sclerosis B. Testing To demonstrate that the compounds inhibit the activity of MIP-1 α or RANTES several assays may be employed. One assay utilizes a microphysiometer, which uses a patented silicon-based light addressable potentiometπc sensor to continuously monitor subtle changes in extracellular pH levels. These changes result from the generation of acidic metabolites excreted by living cells into their immediate microenvironment during basal and stimulated conditions. It has been previously demonstrated by microphysiometry that THP-1 cells, which have been shown to express the chemokine receptors, CCR1 and CCR2, respond dose- responsively to their respective chemokines, including MIP-1 , RANTES and MCP-1 (a ligand for CCR2). See, e.g., Hirst, M. ef al., "Chemokine receptors," Journal of NIH Research (1995), Vol. 80. Another assay which may be used to demonstrate the ability of the compounds to inhibit the activity of MIP-1 α and RANTES is based on the measurement of intracellular Ca 2+ concentrations and/or increases in intracellular [ 3 H] mositol phosphate release from MIP-1 α and RANTES stimulated cells. Ligand binding to the CCR1 receptor results in G-protein induced activation of phospho pase C, which leads to the conversion of phosphatidyl mositol phosphate to mositol phosphate and diacyglycerol. Inositol phosphate in turn binds to a receptor located at intracellular sites to release Ca 2+ into the cytoplasm In addition to Ca 2+ concentration increases due to release from intracellular stores, binding of mositol phosphate to its receptor ieads to an increased flux of extracellular calcium across the membrane and into the cell Thus the activation of the CCR1 receptor by MIP-1α and RANTES and, subsequently, inhibition of the activation by the compounds of the invention can be determined by assaying for an increase in free intracellular Ca 2+ levels. Typically this can be achieved by the use of calcium- sensitive fluorescent probes such as quin-2, fura-2 and ιndo-1. Alternatively, functional activation or inhibition of the activation of the CCR1 receptor can be measured by quantitation of [ 3 H] mositol phosphate release from the cell pre-labeled with [ 3 H] inositol Standard in vitro binding assays may be employed to demonstrate the affinity of the compounds for the CCR1 receptor (thereby inhibiting the activity of MIP-1 α and RANTES by competitive binding to the receptor). See, e.g., Neote, K. ef al., Cell (1993), Vol. 72, pp. 415- 425 One particular assay employs the use of HEK293 cells which have been stably transfected to express human CCR1 receptor Standard in vivo assays which may be employed to demonstrate the compounds usefulness as anti-inflammatory agents are the animal model for experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis and the adjuvant-induced arthritis (AIA) model for rheumatoid arthπtis C. General Administration Administration of the compounds of the invention, or their pharmaceutically acceptable salts, in pure form or in an appropriate pharmaceutical composition, can be carried out via any of the accepted modes of administration or agents for serving similar utilities Thus, administration can be, for example, orally, nasally, parenterally, topically, transdermally, or rectally, sublmgualiy, intramuscular, subcutaneously, or intravenously in the form of solid, semi-solid, lyophilized powder, or liquid dosage forms, such as for example, tablets, suppositories, pills, soft elastic and hard gelatin capsules, powders, solutions, suspensions, or aerosols, or the like, preferably in unit dosage forms suitable for simple administration of precise dosages The compositions will include a conventional pharmaceutical carrier or excipient and a compound of the invention as the/an active agent, and, in addition, may include other medicinal agents, pharmaceutical agents, carriers, adjuvants, etc Generally, depending on the intended mode of administration, the pharmaceutically acceptable compositions will contain about 1 % to about 99% by weight of a compound(s) of the invention, or a pharmaceutically acceptable salt thereof, and 99% to 1 % by weight of one or more suitable pharmaceutical excιpιent(s) Preferably, the composition will be about 5% to 75% by weight of a compound(s) of the invention, or a pharmaceutically acceptable salt thereof, with the rest being suitable pharmaceutical excipients The preferred route of administration is oral, using a convenient daily dosage regimen which can be adjusted according to the degree of severity of the disease-state to be treated For such oral administration, a pharmaceutically acceptable composition containing a compound(s) of the invention, or a pharmaceutically acceptable salt thereof, is formed by the incorporation of any of the normally employed excipients Such excipients include non-toxic and chemically compatible fillers, binders, disintegrants, buffers, preservatives, anti-oxidants, lubricants, flavorings, thickeners, coloring agents, emulsifiers, and the like, for example, pharmaceutical grades of mannitol, lactose, starch, pregelatinized starch, magnesium stearate, sodium saccharine, talcum, cellulose ether derivatives, glucose, gelatin, sucrose, citrate, cyciodextrin, propyl gallate, and the like. Such compositions take the form of solutions, suspensions, tablets, pills, capsules, powders, sustained release formulations and the like. Preferably such compositions will take the form of capsule, caplet or tablet and therefore will also contain a diluent such as lactose, sucrose, dicalcium phosphate, and the like; a disintegrant such as croscarmellose sodium or derivatives thereof; a lubricant such as magnesium stearate and the like; and a binder such as a starch, gum acacia, polyvinylpyrrolidone, gelatin, cellulose ether derivatives, and the like. The compounds of the invention, or their pharmaceutically acceptable salts, may also be formulated into a suppository using, for example, about 0.5% to about 50% active ingredient disposed in a carrier that slowly dissolves within the body, e.g., polyoxyethylene glycols and polyethylene glycols (PEG), e.g., PEG 1000 (96%) and PEG 4000 (4%), and propylene glycol. Liquid pharmaceutically administrabie compositions can, for example, be prepared by dissolving, dispersing, etc., a compound(s) of the invention (about 0.5% to about 20%), or a pharmaceutically acceptable salt thereof, and optional pharmaceutical adjuvants in a carrier, such as, for example, water, saline, aqueous dextrose, aqueous cyciodextrin, glycerol, ethanol and the like, to thereby form a solution or suspension. If desired, a pharmaceutical composition of the invention may also contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, antioxidants, and the like, such as, for example, citric acid, sorbitan monolaurate, triethanoiamine oleate, butylated hydroxytoluene, etc. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington's Pharmaceutical Sciences, 18th Ed., (Mack Publishing Company, Easton, Pennsylvania, 1990). The composition to be administered will, in any event, contain a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, for treatment of an inflammatory disorder alleviated by the inhibition of the activity of the chemokines, MIP-1 α and RANTES. The compounds of the invention, or their pharmaceutically acceptable salts, are administered in a therapeutically effective amount which will vary depending upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of the compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular disease-states, and the host undergoing therapy Generally, a therapeutically effective daily dose is from about 0.014 mg to about 14 0 mg/kg of body weight per day of a compound of the invention, or a pharmaceutically acceptable salt thereof, preferably, from about 0 14 mg to about 10 0 mg/kg of body weight per day; and most preferably, from about 1 4 mg to about 7 0 mg/kg of body weight per day For example, for administration to a 70 kg person, the dosage range would be from about 1 0 mg to about 1 0 gram per day of a compound of the invention, or a pharmaceutically acceptable salt thereof, preferably from about 10 mg to about 700 mg per day, and most preferably from about 100 mg to about 500 mg per day Preferred Embodiments One aspect of the invention are the compounds of formula (la) as defined above in the Summary of the Invention Of these compounds, a preferred group of compounds of formula (la) is that group of compounds wherein R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsuifinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, am oalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycioalkylalkyl, cycloalkylammo, cycloalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkylamιno)aralkyl, (hydroxyalkyl)hιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylamino, monoaralkylamino, aminoalkylamino, heterocyclylammo, (cycioalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonyiammo, alkenylcarbonylamino, cycloalkylcarbonyiamino, arylcarbonylamino, heterocyciylcarbonylamino, hatoalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl)(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoaryiaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkyicarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyi, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylaminocarbonyl, (amιnocarbonylalkyl)amιnαcarbonyi, (rπonoalkylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl. dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyl)(monoaryl)ureιdo, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, aminocarbonylglyαnamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyi)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycinamido, (arytcarbonyl)(alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamido, (monoaralkylamιnocarbonyl)(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoaryiaminocarbonyl)(alkyl)giycιnamιdo, glycmamidoalkyl, alanmamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl. Of this group of compounds, a preferred subgroup of compounds is that group of compounds wherein: R 4 is -O-, -N(R 7 )- or -C(R 8 )-; R 5 is an alkylene chain; R 7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, amino, monoalkylamino, dialkylamino, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylaikylcarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, arylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl)(alkyl)amino, aralkylcarbonyiamino, (aralkylcarbonyl)(alkyl)amino, alkylcarbonyiaminoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyl)aminoalkyl, aralkylcarbonylaminoaikyl, heterocyciylcarbonylaminoalkyl, (aralkylcarbonyl)(alkyl)aminoalkyl, arylsulfonylamino, alkylsulfonylaminoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido. ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, aminoalkyl, monoalkylaminoalkyl, dialkytaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl. Of this subgroup of compounds, a preferred class of compounds is that group of compounds wherein: R 4 is -O-; R 5 is methylene; and R 6 is -C(O)-. Of this class of compounds, a preferred subclass of compounds is that group of compounds wherein: R 1a is one or more substituents independently selected from the group consisting of halo, alkyl, cycloalkyl, cycioalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, azidoalkyl, monoalkylureidoalkyl, (alkoxycarbonylalkyl)ureidoalkyl, hydroxyalkyiaminoalkyl, aryloxyalkylcarbonyloxyalkyl, araikoxyalkylcarbonyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen and halo; R 3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, aminoalkoxy, cycloalkyl, cycioalkylaminoalkyl, aralkyl, hydroxyalkyl, (monoalkylamιno)aralkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylam o, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonyiamino, (alkyicarbonyl)(alkyl)amιno, alkyisulfonylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, alkylsulfonylaminoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsuifonyl)(alkyl)amιnoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιπocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιπocarbonyl, dialkylaminocarbonylalkyl, hydroxyamidino, ureido, monoalkylureido, moπoarylureido, monoaralkylureido, (monoalkyl)(monoaryl)ureιdo, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkytureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl monohaloalkylureidoalkyl, (haioalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycmamido, aminocarbonylgiycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxy carbonylalkylcarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycinamido, (arylcarbonyl)(alkyi)glycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkyiamιnocarbonyl)(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo (monoarylamιnocarbonyl)(alkyl)glycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl. Preferred compounds within this subclass of compounds are selected from the group consisting of the following compounds: (2S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)piperazιne; 1-((phenoxy)methyl)carbonyl-2-ethyl-4-(4-fluorobenzyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-ethyipiperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(methoxymethyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-((acetylamιno)methyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-((4-fluorobenzyl)amιno)ethyl)-4-(4- fluorobenzyl)piperazιne; 1 -((4-chlorophenoxy)methyl)carbonyl-2-(2-((methyl)amιno)ethyl)-4-(4- fluorobenzyl)pιperazιne; 1-((4-chiorophenoxy)methyl)carbonyl-2-(2-((2-hydroxyethyi)amιno)ethyl)-4-(4- fluorobenzyl)piperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-((((4-chlorophenoxy)- methyl)carbonyl)oxy)methyl-5-methylpιperazιne; 4-(4-fluorobenzyl)-1-((4-chlσrophenoxy)methyl)carbonyl-3-(ethoxycarbonyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carboπyl-3-(methoxycarbonyl)methylpιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-((methoxy)methyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-(methoxy)ethyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxy-2-(4-methylphenyl)- ethyl)pιperazιne; 4-(4-fiuorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxypropyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chiorophenoxy)methyl)carbonyl-3-(2-hydroxybut-4-ynyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-5-(2-hydroxy-2- methylpropyi)piperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxyethyl)pιperazιne ; 1-((4-chlorophenoxy)methyl)carbonyl-3-(2-((2-hydroxyethyl)amιno)ethyl)-4-(4- fluorobenzyl)piperazιne; (c;s / )-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,3-dιmethylpιperazιne; (2S,5R)-1-((4-chloro-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazine; (2S,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,5-dιmethylpιperazιne, (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlo r ophenoxy)methyl)carbonyl-2-methyl-5-(2- methylthιo)ethylpιperazιne, (2 5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(benzyloxy)methyl- piperazine, (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-(((2-hydroxyethyl)thιo)methyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(Λ '-(ethoxycarbonylmethyl) ureιdo)methyl)pιperazιne, (2R,5S)-1 -((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-((amιno)carbonyloxy)methyl-4-(4- fluorobenzyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-((acetyl)methyl)pιperazιne, (2 5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1- hydroxy-1-(phenyl)methyl)pιperazιne, (2f?,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1- hydroxybutyl)piperazine, (2f?,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-((dιethylamιno)methyl)pιperazιne, (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobeπzyl)- 5-((dιmethylamιno)methyl)pιperazιne, (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-(((cyclopropyl)amιno)methyl)pιperazιne, (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((morpholιn-4- yl)methyl)pιperazιne, (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((pιperazιn-1- yl)methyl)pιperazιne, (c/s)-1 -((3,4,5-tnmethoxyphenoxy)methyl)carbonyl-2,6-dimethyl-4-(4-fluorobenzyl)piperazine, (c/s)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,6-dιmethylpιperazιne, 1-((phenoxy)methyt)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, 1-((2-(acetylamιno)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-hydroxypropyl)-4-(4-fluorobenzyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-hydroxybut-3-enyl)-4-(4-fluorobenzyl)piperazine; 1-((4-chlorophenoxy)methyl)carbony!-3-trifluoromethyl-4-(4-fluorobenzyl)piperazine; and (frans)-1-((4-chloro-2-((4-(2,5-di(trifluoromethyl)phenylcarbonyl)piperazin-1- yl)methyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine. Of this subclass of compounds, a preferred group of compounds is that group of compounds wherein: R 1a is one or more substituents independently selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl, azidoalkyl, monoalkylureidoalkyl, aryloxyalkylcarbonyloxyalkyl, and heterocyclylalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, nitro, cyano, aminoalkoxy, cycioalkylaminoalkyl, hydroxyalkyl, (monoalkyiamino)aralkyl, alkoxyalkyl, amino, monoalkylamino, dialkylamino, monoaralkylamino, alkylcarbonyiamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)aminoalkyl, (cycloalkyalkyl)aminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, alkylsuifonylaminoalkyl, (alkylsulfonyl)(alkyl)aminoalkyl, aryisulfonylaminoalkyl, (aryisuifonyl)(alkyl)aminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyt, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (aminocarbonyialkyl)aminocarbonyl, (aminoalkyl)aminocarbonyl, (hydroxyalkyl)aminocarbonyl, hydroxyamidino, ureido, monoalkylureido, monoaryiureido, monoaralkylureido, (monoalkyl)(monoaryl)ureido, (haloalkylcarbonyl)ureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureidoalkyl, (alkoxycarbonylalkyl)ureidoalkyl, glycinamido, monoalkylglycinamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl)glycinamido, (aminocarbonyl)(alkyl)glycinamido, (alkoxycarbonylalkyicarbonyl)(alkyl)glycinamido, (alkoxycarbonylamιnoalkytcarbonyl)glycιnamιdo, arylcarbonylglycinamido, (arylcarbonyl)(alkyl)glycιnamido, (monoaralkylamιnocarbonyl)(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyl)(alkyl)glycιnamιdo, alan amido, heterocyclyl and heterocyclylalkyl. Preferred compounds within this group of compounds in this subclass group of compounds are selected from the group consisting of the following compounds: 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; 1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chtorophenoxy)methyl)carbonyl-2-ethylpιperazιne; (2R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-propylpιperazιne; (2S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-propylpιperazιne; 4-(4-fluorobenzyl)-1-(((4-chlorophenoxy)methyl)carbonyi)spiro[cyclopropane-1 ,2'-pιperazιne], 1-((4-chlorophenoxy)methyl)carbonyl-2-hydroxymethyl-4-(4-fluorobenzyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-(methoxy)ethyl)pιperazιne; 1 -((4-chlorophenoxy)methyl)carbonyl-2-(2-((2-methylpropyl)amιno)ethyl)-4-(4- fluorobenzy piperazine; 1-((4-chlorophenoxy)methyl)carbonyl-3-methyl-4-(4-fluorobenzyt)pιperazιne; 1-((4-chlorophenoxy)methyl)carbonyl-4-(4-fluorobeπzyl)-5-methylpιperazιne; (2R)-1 -((4-chlorophenoxy)methyi)carbonyl-3-methyl-4-(4-fluorobenzyl)pιperazιne, (2S)-1 -((4-chtorophenoxy)methyl)carbonyl-3-methyl-4-(4-fluorobenzyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(hydroxymethyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyi)carbonyl-3-(2-hydroxyethyl)pιperazme; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(((methyl)ureιdo)methyl)pιperazιne, (2R,3R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,3-dιmethylpιperazιne, (c/s)-1-((4-chlorophenoxy)methyl)carbonyl-3,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-(((4-chlorophenoxy)- methyl)carbonyl)oxy)ethyl-5-methylpιperazιne; (2f?,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5- ((hydroxy)methyl)piperazine; (2f.,5R)-4-(4-fluorobenzyl)-1-((4-chiorophenoxy)methyl)carbonyl-2-methyl-5-((methoxy)- methyl)pιperazine; (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1- methylethyl)piperazine; (2R,5f?)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1- hydroxyethyl)piperazine; (2R,5/?)-4-(4-fluorobenzyl)-1 -((4-chiorophenoxy)methyl)carbonyl-2-methyl-5-(1 -hydroxyprop-3- enyl)piperazine; (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fIuorobenzyl)- 5-((cyano)methyl)piperazιne; (2f?,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((1 ,2,4-tπazol-2- yi)methyl)pιperazine; (2f?,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5- ((tetrazolyl)methyl)piperazine; (3S,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3,5-dιmethylpιperazιne; 1-((4-chloro-3-nitrophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazine; (frans)-1 -((4-chloro-2-methylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)piperazine; (fraπs)-1-((4-chloro-2-(diethylamino)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; (fraπs)-1-((4-chloro-2-hydroxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; (fraπs)-1-((5-chloro-2-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyt)piperazine; (fraπs)-1-((4-chloro-2-((ethyl)(1-methylbutyl)amιnomethyl)phenoxy)methyl)carbonyl-2,5- dimethyl-4-(4-fluorobenzyl)piperazine; 1-((4-chloro-2-amιnophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; 1-((4-chloro-3-nitrophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyi)piperazine; (frans)-1-((4-chloro-2-(benzylamino)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; (fraπs)-1-((4-chloro-2-((1-methylbutyl)amino)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)piperazine; (frans)-1-((4-chloro-2-(/so-propylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (fraπs)-1-((4-chloro-2-(Λ/'-(2,4-dιchlorophenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(Λ '-(4-nιtrophenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(Λ/'-(4-methylphenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(Λ/'-benzylureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-((cyclopropylmethyl)amιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl- 4-(4-fluorobenzyl)pιperazιne, (fraπs)-1-((4-chloro-2-(phenylamιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(acetylamιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyi)pιperazιne, (fraπs)-1-((4-chloro-2-((methylamιno)(phenyl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(1-(phenylsulfonyl)(methyl)amιnoethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frat.s)-1-((4-chloro-2-(1-(acetyl)(methyl)amιnoethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (frans)-1 -((4-chloro-2-(1-(Λ/-methyl-Λ/'-ethylureιdo)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl- 4-(4-fluorobenzyl)pιperazιne, (fraπs)-1-((4-chioro-2-(1-((methyl)(ethyl)amιno)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobeπzyl)pιperazιne, (frans)-1-((4-chioro-2-(1-(dιmethylamιno)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (2R)-1-((4-chloro-2-((4-f-butoxycarbonylpιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2- methyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-((piperazιn-1-yi)methyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyi)pιperazιne; (fraπs)-1-((4-chioro-2-(oxazol-2-ylamιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; 1-((4-chloro-2-(morpholin-4-ylmethyl)phenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyl)pιperazιne; (frans)-1-((4-bromo-2-formylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)pιperazιne; (frans)-1-((4-fluoro-3-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, 1-((4-chloro-2-methoxycarbonylphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-methoxycarbonylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; 1-((4-chloro-2-amιnocarbonylphenoxy)methyl)carboπyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzy piperazine; (frans)-1-((4-chloro-2-formylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)pιperazιne; (fraπs)-1 -((4-chloro-2-cyanophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπs)-1-((3-cyanophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-methyl-2-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; (frans)-1-((3-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπs)-1-((4-methyl-2-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; (frans)-1-((2-methoxycarbonylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)piperazιne; (frans)-1-((3-nitrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-acetyl-2-(amιnocarbonyt)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; (fraπs)-1-((4-nιtro-3-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((5-nitro-2-methylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobeπzyl)pιperazιne; (frat7s)-1-((4-amιno-3-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1 -((5-nιtro-2-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1 -((2-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1 -((3-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frat?s)-1-((4-methoxy-2-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; (frans)-1 -((5-methoxy-2-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; (frans)-1-((2-((2-hydroxyethyl)amιnocarbonyl)phenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (frans)-1-((2-((2-hydroxyethoxy)carbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; (frans)-1-((2-(2-hydroxyethoxy)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzy piperazine; (fraπs)-1-((2-acetyl-4,5-dιmethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (fraπs)-1-((5-methoxy-2-(methoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(/V'-methylureιdo)- amιno)methyl)pιperazιne, (frans)-1-((4-methyl-2-formyiphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; (frans)-1-((3-chloro-5-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; (frans)-1-((2-methoxy-5-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; (frans)-1-((2-(hydroxymethyl)phenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; (frans)-1 -((2-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, 1-((4-chtorophenoxy)methyl)carbonyl-2-(2-azιdoethyl)-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(phthatιmido)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazιne; (frans)-1-((4-chloro-2-(maleimido)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazιne; (frans)-1-((4-chloro-2-((4-(benzylcarbonyl)pιperazιn-1-yl)methyl)phenoxy)methyl)-carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (fraπs)-1-((4-chioro-2-((4-((2,3,4-trifluorophenyl)amιnocarbonyl)piperazin-1- yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyi-4-(4-fluorobeπzyl)pιperazιne; (frans)-1-((4-chloro-2-((4-((2-fluorophenyl)amιnocarbonyl)pιperazin-1- yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; (fraπs)-1-((4-chloro-2-((Λ/'-(2,6-difiuorophenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(ethenylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazιne; (frans)-1-((4-chloro-2-(cyclopropytcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazιne; (frans)-1-((4-chloro-2-(cyclopentylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; (fraπs)-1-((4-chloro-2-((furan-2-yl)carbonylamιno)phenoxy)methyi)carbonyl-2,5-dιmethyl-4-/4- fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(phenylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; (trans)- . -((4-chloro-2-((/V-(3-methoxyphenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; (frans)-1-((4-chloro-2-((A/'-(methoxycarbonylmethylcarbonyl)-A/- (methyl)glycιnamido)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazιne; (frans)-1-((4-chloro-2-((Λ/'-(2-methoxycarbonylethyl)carbonyl-W- (methyl)glycinamido)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazιne; (frans)-1-((4-chloro-2-((/V'-(3-methylbenzyl)amιnocarbonyl-Λ/- (methyl)glycιπamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (fra/7s)-1-((4-chloro-2-((Λ/'-(3-tπfluoromethyl-4-fluorophenyl)carbonyl--V- (methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(( V'-(4-methylbenzyl)amιnocarbonyl-Λ/- (methyl)glycmamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (trans)-1 -((4-chloro-2-((Λ/-(3-chlorophenyl)carbonyl-Λ. '- (methyl)giycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-((Λ/-(4-fluorobenzyl)amιnocarbonyl-Λf- (methyl)giycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(Λ/'-(2-ιodophenytcarbonyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπs)-1-((4-chloro-2-(Λ/'-(2,3-dιfluorophenylcarbonyl)glycιnamιdo)phenoxy)-methyl)carbonyl- 2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(/v " -((4-phenoxyphenyl)aminocarbonyl)glycinamido)phenoxy)- methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπs)-1-((4-chloro-2-(Λ/-(2,4-dιflurophenylcarbonyl)glycιnamιdo)phenoxy)methyl)-carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chioro-2-((2-ιodophenylcarbonyl)amιnomethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιπe, (frans)-1-((4-chloro-2-((ethoxycarbonyimethyicarbonyl)amιnomethyl)phenoxy)-methyl)carbonyl- 2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(Λ '-(3-chloropropyl)ureιdomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl- 4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(/V'-(2-fluoro-6-trιfluoromethylphenyl)ureιdomethyl)phenoxy)- methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-((3-fluorophenyl)carbonylamιnomethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (frans)-1 -((4-chloro-2-(Λ/'-(2-(ethoxycarbonyl)ethyl)ureιdomethyl)phenoxy)-methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyt)pιperazιne, (2S)-1-((4-chloro-2-(ureιdo)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-((2,5-dι(tπfluoromethyl)phenyl)carbonylamιnomethyl)- phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; and (frans)-1-((4-chloro-2-(/V'-(2-(phenyl)cyclopropyl)ureιdomethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne A more preferred group of compounds in this subclass group of compounds are those compounds wherein R 1a IS one or more substituents independently selected from the group consisting of alkyl and hydroxyalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro, R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of halo, alkyl, alkoxy, formyl, nitro, cycioalkylaminoalkyl, hydroxyalkyl, am o, aikylcarbonylammo, haloalkylcarbonylammo, alkoxyalkyicarbonylamino, alkoxycarbonylalkylcarbonylamino, aikylsulfonylamino. ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyl, alkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonyialkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyi, hydroxyamidino, ureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, glycmamido, monoalkylglycinamido, aminocarbonylglycmamido, (alkoxyaikylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, aianinamido, and heterocyclylalkyl Preferred compounds within this more preferred group of compounds in this subclass group of compounds are selected from the group consisting of the following compounds (fraπs)-1-((4-chloro-3-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chtoro-2-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne, (frans)-1 -((4-chioro-2-(amιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazιne; (2R,5S)-1-((4-chloro-2-(amιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; (2S,5R)-1-((4-bromo-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (2R,5S)-1-((3-hydroxy-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzy piperazine; (2S,5f?)-1-((4-nitro-3-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyt)pιperazιne; (2R)-1 -((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-hydroxyethyl)pιperazιne; (frans)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,5-dimethylpιperazιne; (2R,5S)-4-(4-fluorobenzyl)-1-((4-chtorophenoxy)methyl)carbonyl-2,5-dιmethylpιperazιne; (frans)-1-((4-chloro-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (2R,5S)-1-((4-chloro-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fiuorobenzy piperazine; (2f.,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-hydroxyethyl)- 5-methylpιperazιne; (2R,6R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,6-dιmethylpιperazιne, (frans)-1-((4-chloro-2-methoxyphenoxy)methyt)carbonyl-2,5-dιmethyl-4-(4- fluorobeπzyl)pιperazιne; 1-((4-chloro-2-(hydroxymethyl)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (2R,5S)-1-((4-chloro-3-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-(1-hydroxyethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzy piperazine; (frans)-1-((4-chloro-2-(aminomethyi)phenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; (fraπs)-1-((4-chloro-2-(ureidomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazιne; (frans)-1 -((4-chloro-2-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, 1-((4-chloro-2-(acetylamιno)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (fraπs)-4-(4-fluorobenzyl)-1-((2-acetylamιno-4-chlorophenoxy)methyl)carbonyl- 2,5-dιmethylpιperazιne; (frans)-1-((4-chloro-2-(propylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (fraπs)-1-((4-chloro-2-(methoxymethytcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(2-(methoxycarbonyl)ethyicarbonylamιno)phenoxy)-methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(2-(ethoxycarbonyl)ethylcarbonylamιno)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(methylsulfonyiammo)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-(bromomethylc3rbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobeπzyOpiperazine; (2R)-1-((4-chloro-2-(glycιnamιdo)phenoxy)methyl)carbonyl-2-methyl-4-(4- fiuorobenzyOpiperazine; (frans)-1-((4-chloro-2-((Λ/'-methylglycιnamιdo)pheπoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((4-chloro-2-(alanιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((4-chloro-2-((amιnocarbony0glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-((amιnocarbony0(methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(Λ/'-ethyluredιo)phenoxy)methy0carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-(ethyicarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1 -((4-chloro-2-amιno-5-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, dihydrochloπde salt; (frans)-1-((4-chloro-2-(((ethyl)amιno)methyl)phenoxy)methy0carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(((diethyl)amino)methyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-(((cyclopropy0amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(((dιmethy0amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-(((methyl)amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (fraπs)-1-((4-chtoro-2-((amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((4-methylpιperazιn-1-yl)methyθphenoxy)methyt)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-((piperazin-1-yl)methyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(ethylamιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (fraπs)-1 -((4-chloro-2-(1 -(methylamιno)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(1-(methylsulfonyl)(methy0amιnoethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (2f?)-1-((4-chloro-2-((pιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazine; (2R,5S)-1-((4-chloro-2-((pιperazιn-1-y0methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((4-f-butoxycarbonylpiperazin-1-yl)methy0phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (fraπs)-1 -((4-chloro-2-(ιmιdazol-1 -ylmethyl)pheπoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-(1-(ιmιdazol-1-yl)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ( rans)-1 -((4-chloro-2-(tπazol-1 -ylmethyl )phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyt)pιperazιne, (frans)-1 -((4-chloro-2-(tetrazol-1 -ytmethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((4-chloro-2-((morpholιn-4-yl)methy0phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (2f?)-1 -((4-chloro-2-amιnocarbonylphenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazine, 1-((4-chloro-2-formylphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (2R,5S)-1-((4-chioro-2-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (2f?)-1-((4-chloro-2-formylphenoxy)methy0carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (fraπs)-1 -((4-chloro-2-(methylamιnocarbonyl)phenoxy)methy0carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((4-chloro-2-((amιnocarbonylmethyl)amιnocarbonyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπs)-1-((4-chloro-2-((2-amιnoethyl)amιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-((4-aminocarbonylphenyl)aminocarbony0phenoxy)methyl)caroonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(hydroxyamιdιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1 -((4-chloro-2-acetyiphenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((2-(aminocarbonyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)pιperazιne; (fraπs)-1-((4-chloro-2-((Λ/'-(trιchtoromethylcarbonyl)ureιdo)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(A/'-(methoxymethylcarbony0giycinamido)phenoxy)methyl)-carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; and (fraπs)-1-((4-chioro-2-(/V'-(ethoxycarbonylamιnocarbonyl)- glycinamido)phenoxy)methy0carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)piperazιne. The most preferred group of compounds within this subclass group of compounds are those compounds wherein R 2 is 4-fluoro and R 3 is phenyl substituted at the 4-posιtιon with chloro and at the 2-posιtion by aminocarbonyl, ureido, or glycmamido.; namely, the compounds selected from the group consisting of the following compounds: (2f?,5S)-1-((4-chloro-2-(amιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(glycιnamido)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (2R)-1-((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (frat7s)-1-((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (2f?,5S)-1-((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; and (2R,5S)-1-((4-chioro-2-(glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine. Of the subgroup of compounds as set forth above, another preferred class of compounds are those compounds wherein: R 5 is methylene; R 7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl. Of this class of compounds, a preferred subclass of compounds are those compounds wherein: R a is one or more substituents independently selected from the group consisting of halo, alkyl, cycloalkyl, cycioalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, cyaπoalkyl, haloalkylcarbonylaminoalkyl, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, azidoalkyl, monoalkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyloxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen and halo; R 3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, aminoalkoxy, cycloalkyl, cycioalkylaminoalkyl, aralkyl, hydroxyalkyl, (monoalkylamιno)aralkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonytamino, haloalkylcarbonylamino, alkoxyalkylcarbonylammo, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyθ(alkyl)amιno, alkylsulfonyiamino, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, alkylsulfonylaminoalkyl, (alkylsulfonyθ(alkyl)amιnoalkyl, arylsulfonyiaminoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyi, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (aminoalkyl)amιnocarbonyl, (hydroxyaikyl)amιnocarbonyl, dialkylaminocarbonylalkyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, (monoalkyi)(monoaryl)ureido, (haloalkylcarbonyl)ureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycinamido, monoalkylglycinamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl)glycinamido, (aminocarbonyl)(alkyl)glycιnamido, (aikoxycarbonylalkylcarbonyl)(alkyl)giycinamido, (alkoxycarbonylaminoalkylcarbonyi)glycinamido, arylcarbonylgiycinamido, (arylcarbonyl)(alkyOglycιnamido, (monoaralkylamιnocarbonyl)glycinamido, (monoaraikylamιnocarbonyθ(alkyl)glycιnamido, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylaminocarbonyl)(alkyl)glycinamido, alaninamido, heterocyclyl and heterocyclylalkyl. A preferred group of compounds in this subclass group of compounds is that group wherein: R 1a is one or more substituents independently selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl, azidoalkyl, monoalkylureidoalkyl, aryloxyalkylcarbonyloxyalkyl, and heterocyclylalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, nitro, cyano, ammoalkoxy, cycioalkylaminoalkyl, hydroxyalkyl, (monoalkylamιno)aralkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonyiamino, heterocyclylcarbonylamino, haloalkylcarbonylammo, alkoxyalkylcarbonylamino, alkoxycarbonyialkylcarbonyiamino, alkylsulfonylammo, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylalkyicarbonylaminoalkyl, alkylsulfonylaminoalkyl, (alkylsulfonyθ(alkyl)amιnoaikyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyl, aminocarbonyl, monoalkylaminocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (aminoalkyl)aminocarbonyl, (hydroxyalkyl)amιnocarbonyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, (monoalkyi)(monoaryi)ureido, (haloalkylcarbonyl)ureido, ureidoalkyl, monoalkylureidoalkyl, dialkytureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkyiureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylgiycinamido, aminocarbonylglycinamido, (alkoxyalkyicarbonyl)glycιnamido, (amιnocarbonyl)(alkyl)glycιnamido, (alkoxycarbonylalkyicarbonyθ(alkyl)glycιnamido, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylgiycinamido, (arylcarbonyθ(alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyl)(alkyl)glycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl. A more preferred group in this subclass group of compounds are those compounds wherein R 1a is one or more substituents independently selected from the group consisting of alkyl and hydroxyalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro, R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of halo, alkyl, alkoxy, formyl, nitro, cycioalkylaminoalkyl, hydroxyalkyl, am o, aikylcarbonylammo, haloalkylcarbonylammo, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, (alkylsulfonyθ(alkyl)amιnoalkyl, alkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, hydroxyamidino, ureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, glycmamido, monoalkylglycmamido, aminocarbonylglyαnamido, (alkoxyalkyicarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylaminoalkylcarbonyl)glycinamido, alaninamido, and heterocyclylalkyl An even more preferred group of compounds in this subclass group of compounds are those compounds wherein R 2 is 4-fluoro and R 3 is phenyl substituted at the 4-posιtιon with chloro and optionally substituted at the 2-posιtιon by aminocarbonyl, ureido, or glycmamido Preferred compounds in this group selected from the group consisting of the following compounds- (fraπs)-1 -((4-chlorophenylamino)methyi)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine 1-((4-chloro-2-(amιnocarbonyl)phenylamιno)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazine; and 1-((4-chlorophenylamιno)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne;. Of the subgroup of compounds as set forth above, another preferred class of compounds are those compounds wherein. R 5 is methylene, each R 8 is independently selected from the group consisting of hydrogen, alkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkyialkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylammo, alkylcarbonylammoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, heterocyclylcarbonylaminoalkyl, arylsulfonylamino, alkylsulfonylaminoalkyl, ureido, monoalkylureido, monohaioalkylureido, ureidoalkyl, monoalkylureidoalkyl, monohaloalkylureidoaikyl, ammoalkyl, monoalkylaminoalkyl, and dialkylammoalkyl A preferred subclass of compounds of this class of compounds are those compounds wherein R a is one or more substituents independently selected from the group consisting of halo, alkyl, cycloalkyl, cycioalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, cyanoalkyl, haloalkylcarbonylammoalkyl, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, azidoalkyl, monoalkylureidoalkyl, (alkoxycarbonylalkyi)ureιdoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyloxyalkyl aralkoxyalkylcarbonyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen and halo; R 3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, aminoalkoxy, cycloalkyl, cycioalkylaminoalkyl, aralkyl, hydroxyalkyl, (monoalkylamιno)aralkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonyiamino, alkoxyalkylcarbonyiamino, alkoxycarbonylalkylcarbonylamino, (alkyicarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonyiaminoalkyl, (alky!carbonyO(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, dialkylaminocarbonylalkyl, hydroxyamidino, ureido, monoalkylureido, monoaryiureido, monoaralkylureido, (monoalkyO(monoaryl)ureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoaryiureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylgiycmamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnam-do, (amιnocarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycinamido, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycmamido, (arylcarbonyθ(alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyθ(alkyl)giycιnamιdo, (monoaryiamιnocarbonyl)giycιnamιdo, (monoarylamιnocarbonyθ(alkyl)glycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl. A preferred group of compounds within this preferred subclass of compounds are those compounds wherein: R a is one or more substituents independently selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl, azidoalkyl, monoalkylureidoalkyl, aryloxyalkylcarbonyloxyalkyl, and heterocyclylalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, nitro, cyano, ammoalkoxy, cycioalkylaminoalkyl, hydroxyalkyl, (monoalkylamιno)aralkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkyicarbonylamino, alkylsulfonylammo, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylalkylcarbonylammoalkyl, alkylsulfonyiaminoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyi, arylsulfonylammoalkyl, (arylsulfonyθ(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyi, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkyiureido, (monoalkyl)(monoaryl)ureιdo, (haioaikylcarbonyl)ureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyi, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureidoalkyl, (alkoxycarbonylalkyl)ureidoalkyl, glycinamido, monoalkylgiycinamido, aminocarbonylgiycinamido, (alkoxyalkylcarbonyi)glycιnamιdo, (aminocarbonyθ(alkyl)glycιnamido, (alkoxycarbonylalkylcarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycinamido, (arylcarbonyl)(alkyl)glycinamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)giycιnamιdo, (monoarylamιnocarbonyl)(alkyOgiycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl. A more preferred group of compounds within this subclass of compounds are those compounds wherein: R 1a is one or more substituents independently selected from the group consisting of alkyl and hydroxyalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of halo, alkyl, alkoxy, formyl, nitro, cycioalkylaminoalkyl, hydroxyalkyl, am o, aikylcarbonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylsulfonylamino, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyl, alkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, hydroxyamidmo, ureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, glycmamido, monoalkylglycinamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, alaninamido, and heterocyclylalkyl An even more preferred group of compounds of this subclass group of compounds are those compounds wherein R 2 is 4-fluoro; R 3 is phenyl substituted at the 4-posιtιon with chloro and optionally substituted at the 2-posιtιon by aminocarbonyl, ureido, or glycmamido; and one R 8 is hydrogen and the other R 8 is selected from the group consisting of ammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylcarbonylammoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, heterocyclylcarbonylammoalkyl, aryisulfonylamino, alkylsulfonylaminoalkyl, ureido, monoalkylureido, monohaloalkylureido, ureidoalkyl, monoalkylureidoalkyl, monohaloalkylureidoalkyl, and ammoalkyl Preferred compounds in this even more preferred group are those compounds selected from the group consisting of the following compounds: (frat7s)-1-(2-(4-chlorophenyl)-3-(methylsulfonylamιno)propyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; (frat)s)-1-(2-(4-chlorophenyl)-3-(acetylamιno)propyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-(2-(4-chlorophenyl)-2-(methyisulfonylamιno)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ( rans)-1-(2-(4-chlorophenyl)-2-(acetylamιno)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frar7s)-1-(2-(4-chlorophenyl)-2-(amιno)ethyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzy0pιperazιne, (frans)-1-(2-(4-chlorophenyl)-2-(ureido)ethyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, (frat7s)-1-(2-(4-chlorophenyl)-3-(ureido)propyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frat7s)-1-(2-(4-chlorophenyl)-3-(amino)propyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)piperazine; (frans)-1-(2-(4-chlorophenyl)-3-(f-butoxycarbonylamino)propyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-(2-(4-chlorophenyl)-2-((ethoxycarbonylmethylcarbonylamino)ethyl)carbonyl-2,5- dimethyl-4-(4-fluorobenzyl)piperazine; (frat7s)-1-(2-(4-chlorophenyO-2-(Λ/'-/so-propylureido)ethyOcarbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-(2-(4-chlorophenyl)-2-(Λ/-(2-chloroethyi)ureido)ethy0carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)piperazine; (frat7s)-1-(2-(4-chloropheny0-2-((2-nitrophenyl)carbonylamino)ethyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1 -(2-(4-chlorophenyl)-2-((4-methoxyphenylmethyl)carbonylamino)ethyl)carbonyl-2,5- dimethyl-4-(4-fluorobenzyl)piperazine; (fraπs)-1-(2-(4-chloropheny0-2-((2,4-dinitrophenyl)sulfonylamino)ethyl)carbonyl-2,5-dimethyl-4- (4-fluorobenzyl)piperazine; (frans)-1-(2-(4-chlorophenyl)-2-(cyclopropylcarbonylamino)ethyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-(2-(4-chlorophenyl)-2-((2-cyclopropylethyl)carbonylamino)ethyl)carbonyl-2,5-dimethyl- 4-(4-fluorobenzyl)piperazine; (frans)-1-(2-(4-chlorophenyl)-3-((2-methylpropyl)carbonylamino)propyl)carbonyl-2,5-dimethyl-4- (4-fluorobenzyl)piperazine; (frans)-1-(2-(4-chloropheny0-3-(cycloppentylcarbonylamino)propyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frat7s)-1-(2-(4-chlorophenyl)-3-(A/'-(f-buty0ureido)propy0carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)piperazine; (frans)-1-(2-(4-chlorophenyl)-3-(Λ/-(ethyl)ureido)propyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-(2-(4-chloropheny0-3-(Λ/'-(3-choropropy0ureιdo)propyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, and (frans)-1-(2-(4-chlorophenyl)-3-((morpholin-4-yl)carbonylamino)propyl)carbonyl-2,5-dimethyl-4- (4-fluorobenzyl)pιperazιne. Of the compounds of formula (la), another preferred group of compounds are those compounds wherein: R 3 is a heterocyclic πng system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, ammo, monoalkylamino, dialkylammo, monoarylamino, monoaralkylamino aikylcarbonylammo, alkoxycarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylammo, (alkylcarbonyl)(alkyOamιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylam oalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido Of this group of compounds, a preferred subgroup of compounds is that group of compounds wherein. R 4 is -0-, -N(R 7 )- or -C(R 8 )-, R 5 is an alkylene chain, R 7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, am o, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylammo, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylammo, (alkylcarbonyθ(alkyl)amιno, aralkylcarbonylamino, (aralkylcarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, cycloalkylcarbonylammoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyi)amιnoalkyl, aralkylcarbonylammoalkyl, heterocyclylcarbonylaminoalkyl, (aralkylcarbonyl)(alkyl)amιnoalkyl, arylsulfonylammo, alkylsulfonylaminoalkyl, ureido, monoalkylureido, monohaloalkyiureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl Of this subgroup of compounds, a preferred class of compounds are those compounds wherein R 5 is methylene; and Of this class of compounds, a preferred subclass group of compounds are those compounds wherein: R 1a is one or more substituents independently selected from the group consisting of halo, alkyl, cycloalkyl, cycioalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, azidoalkyl, monoalkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, hydroxyalkylammoalkyl, aryloxyaikylcarbonyloxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl; and R 2 is one or more substituents independently selected from the group consisting of hydrogen and halo A preferred group of compounds in this preferred subclass group of compounds are those compounds wherein R 3 is selected from the group consisting of azep yl, acπdinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl, carbazolyl, cmnolinyl, decahydroisoquinolyl, dioxolanyl, furyl, isothiazolyl, qumuclidinyl, imidazolyl, imidazolinyl, imidazolidmyl, isothiazolidmyl, mdolyl, isomdolyl, indolmyl, isoindolmyl, mdanyl, indolizmyl, isoxazolyl, isoxazolid yl, morpholmyl, naphthyπdinyl, oxadiazolyl, octahydromdolyl, octahydroiso dolyl, 2-oxopιperazιnyl, 2-oxopιpeπdιnyl, 2-oxopyrrolιdιnyl, 2-oxoazepιnyl, oxazolyl, oxazolid yi, pipeπdinyl, piperazmyl, 4-pιpeπdonyl, phenazmyl, phenothiazmyl, phenoxazmyl, phthalazinyl, ptendinyl, puπnyl, pyrrolyl, pyrrolidmyl, pyrazolyl, pyrazolidmyl, pyπdinyl, pyrazmyl, pyπmidinyl, pyπdazinyl, quinazolmyl, quinoxalmyl, quinolmyl, qumuclidinyl, isoquinolmyl, thiazolyl, thiazolid yl, thiadiazolyl, tπazolyl, tetrazolyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, thiamorpholmyl, thiamorpholmyl sulfoxide, and thiamorpholmyl sulfone A more preferred group of compounds in this preferred subclass of compounds are those compounds wherein R 3 is benzopyranyl, benzopyranonyl, benzfuranyl, benzofuranonyl, quinolmyl, mdolyl, indolmyl, oxazolyl, imidazolyl, or benzothienyl A preferred compound in this more preferred group is (frans)-1-((benzo[b]pyran-2-on-7- yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne. Another aspect of the invention is a method of treating an inflammatory disorder in a human, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (la) as described above A preferred method is the method of treating inflammatory disorders selected from the group consisting of multiple sclerosis, leukoencephalopathy, encephalomyelitis, Alzheimer's disease, Guillian-Barre syndrome, acute cell-mediated renal transplant rejection, allograft rejection, rheumatoid arthritis, atherosclerosis, uπcaria, angioderma, allergic conjunctivitis, atopic dermatitis allergic contact dermatitis, drug or insect sting allergy and systemic anaphylaxis Another aspect of the invention is a method of treating an inflammatory disorder in a human, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) as described in the Summary of the Invention. A preferred method is that method which comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) wherein R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinytalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, aminoaikoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylamino, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyt, (monoalkylamino)aralkyl, (hydroxyalkyl)hιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, amino, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonyialkylcarbonyiamino, (alkylcarbonyl)(alkyl)ammo, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, aryicarbonylaminoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyθ(alkyl)amιnoalkyl, alkyisulfonyiaminoalkyl, (alkylsulfonyθ(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyθ(alkyl)amιnoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkyiaminocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (monoalkyiamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonylalkyl)amιnocarbonyl, (aminoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidino, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaioalkylureido, (monoalkyl)(monoaryl)ureido, dialkylureido, diarylureido, (haloalkyicarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, moπoarylureidoalkyl, monoaralkylureidoaikyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ιιreidoalkyl, (alkoxycarbonylalkyi)ureιdoalkyl, glycmamido, monoalkylglycmamido, aminocarbonyiglycinamido, (alkoxyalkyicarbonyl)glycιnamido, (aminocarbonyl)(alkyl)glycinamido, (alkoxycarbonylalkylcarbonyθ(alkyi)glycιnamιdo, (alkoxycarbonyiammoalkylcarbonyOglycinamido, arylcarbonylglycmamido, (arylcarbonyl)(alkyOglycιnamιdo, (monoaralkylamιnocarbonyl)glycinamido, (monoaralkylamιnocarbonyl)(alkyl)glycιnamido, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylaminocarbonyl)(alkyl)glycιnamιdo, glycinamidoalkyl, alaninamido, monoalkylalaninamido, alaninamidoalkyl, heterocyclyl and heterocyclylalkyl. An even more preferred method is that method which comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) wherein: R 4 is -0-, -N(R 7 )- or -C(R 8 )-; R 5 is an alkylene chain; R 7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylaikylcarbonylamino, (alkylcarbonyl)(alkyl)amιno, aralkyicarbonylamino, (aralkylcarbonyl)(alkyl)amino, alkylcarbonylammoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, (alkyicarbonyθ(alkyl)amιnoalkyl, aralkylcarbonylaminoalkyl, heterocyclylcarbonylaminoalkyl, (aralkylcarbonyl)(alkyl)amιnoalkyl, arylsulfonylammo, alkylsulfonyiaminoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl. An even more preferred method is that method which comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) wherein: R 5 is methylene; and The most preferred method is that method which comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) wherein- R 2 is one or more substituents independently selected from the group consisting of hydrogen and halo; R 3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, ammoalkoxy, cycloalkyl, cycioalkylaminoalkyl, aralkyl, hydroxyalkyl, (monoalkylamιno)aralkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylamino, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylammoalkyl, (alkoxycarbonyθ(alkyl)amιnoalkyl, alkylsulfonyiaminoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyθ(alkyl)amιnoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, dialkylaminocarbonylalkyl, hydroxyamidmo, ureido, monoalkylureido, monoarylureido, monoaralkylureido, (monoalkyl)(monoaryl)ureιdo, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoaryiureidoalkyl, monoaralkyiureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylgiycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyθ(alkyl)giycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycmamido, (arylcarbonyl)(alkyl)glycinamido, (monoaralkylaminocarbonyOglycmamido, (monoaralkyiamιnocarbonyl)(alkyl)giycιnamιdo, (monoaryiaminocarbonyl)glycinamido, (monoarylamιnocarbonyl)(alkyOglycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl. Particularly preferred is that method which comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) selected from the group consisting of the following compounds 1 -((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(benzyl)pιperazιne, 1-((3,5-dιmethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((2-(hydroxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((4-ιodophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((2-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1 -((4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((2,4-dιchiorophenoxy)methyl)carbonyl-4-(4-chlorobenzy0pιperazιne, 1 -((4-bromo-2-chiorophenoxy)methy0carbonyl-4-(4-chlorobenzyl)piperazine, 1 -((4-chloro-3-nitrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine, 1 -((2-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, l -((4-bromophenoxy)methyl)carbonyl-4-(benzyl)pιperazιne, 1 -((2,4-dιbromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((2-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((2-methoxy-5-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((3,4,5-tπmethoxyphenoxy)methyi)carbonyl-4-(4-fluorobenzyl)pιperazine, 1 -((4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne, 1 -((3-fluoro-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; 1-((3,5-dιmethoxy-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzy0pιperazιne, 1-((4-bromo-2-formylphenoxy)methy0carbonyl-4-(4-chlorobenzyl)pιperazιne; 1-((3-formyl-4-nιtrophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne, 1-((2-amιnocarbonyl-4-chlorophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne, 1-((3,5-dimethoxy-4-bromophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)piperazine; and 1-((2-acetylaminophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)piperazine. Preparation of Compounds of The Invention The following Reaction Schemes are directed to the preparation of compounds of formula (la), formula (lb) and formula (lc). It is understood that those compounds of the invention which are not specifically prepared in the following Reaction Schemes may be prepared by similar synthetic processes with the appropriately substituted starting materials and reagents. It is also understood that in the following descriptions, combinations of the various substituents (e.g., R 1a , R 2 and R 3 substituents) on the depicted formulae are permissible only if such combinations result in stable compounds. For the purposes of convenience only, preparation of compounds of the invention where R 3 is only phenyl are illustrated below. It is understood that other R 3 groups (including other carbocyciic and heterocyclic ring systems) may be prepared in a similar manner. It is also understood that during the preparation of the compounds of the invention, as described below, additional reactive groups (for example, hydroxy, amino or carboxy groups) on the intermediate compounds utilized in the preparation may be protected as needed by the appropriate protecting group by treating the intermediate compound prior to the desired reaction with the appropriate protecting group precursor by methods known to those of ordinary skill in the art. The protecting groups may then be removed as desired by methods known to those of ordinary skill in the art, for example, by acidic or basic hydrolysis. Such protecting groups and methods are described in detail in Greene, T.W. and Wuts, P.G.M., "Protective Groups in Organic Synthesis", 2nd Edition, 1991 , John Wiley & Sons. Also, dimethylpiperazines can be prepared in an asymmetric synthesis according to the method outlined in Mickelson, J.W., Belonga, K.L., Jacobsen, E.J., Journal of Organic Chemistry (1995), Vol. 60, pp. 4177-4123. It should be noted that the only difference in the two groups of compounds covered by formula (la) and formula (lb) as described above in the Summary of the Invention is the required substitution of the piperazine ring in the compounds of formula (la). Accordingly, it is understood that, unless otherwise indicated, the following Reaction Schemes directed to the preparation of the compounds of formula (la) may be used to prepare compounds of formula (Ib), and the following Reaction Schemes directed to the preparation of the compounds of formula (lb) may be used to prepare compounds of formula (la). In addition, compounds of formula (Id) may be prepared in a similar manner as those described herein for compounds of formula (la) and (lb). A. Preparation of Compounds of Formula (C) Compounds of formula (C) are intermediates in the preparation of the compounds of the invention. They are prepared according to the following Reaction Scheme 1 wherein R 1a1 is one or more independently selected R 1a substituents as described above in the Summary of the Invention for compounds of formula (la) (except that R 1a1 can not be ammoalkyl or monoalkylaminoalkyl unless appropriately protected), X is chloro, bromo or lodo; and R 2 is as described above for compounds of formula (la): Reaction Scheme 1 (A) (B) (C) The compounds of formula (A) and formula (B) are commercially available, e.g., from Aldrich Chemical Co. or Sigma Chemical Co., or may be prepared according to methods known to those of ordinary skill in the art. In general, the compounds of formula (C) are prepared by treating a compound of formula (A) in an organic solvent, such as methylene chloride, with an equimolar amount of a compound of formula (B). The reaction mixture is stirred for about 10 to 20 hours at ambient temperature. The reaction mixture is then concentrated to afford a residue which is dissolved in an organic solvent. The compound of formula (C) is isolated from the solution by standard isolation techniques, for example, by filtration, concentration and flash column chromatography B. Preparation of Compounds of Formula (Ga) and Formula (Gb) Compounds of formula (Ga) and formula (Gb) are intermediates in the preparation of compounds of the invention. They are prepared as illustrated in the following Reaction Scheme 2 wherein each R 1a1 is independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, cycioalkylaminoalkyl, (cycloalkylalkyl)amιnoalkyl, haloalkyl, alkenyl, alkynyl, aralkyl, aralkenyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, (alkoxy)aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkyicarbonyl)(alkyOamιnoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, aryloxyaikylcarbonyloxyalkyl, alkoxyalkylcarbonyloxyalkyl, aralkoxyalkyicarbonyloxyalkyl, alkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoaryiaminocarbonylalkyl, monoaralkylammocarbonylalkyl, heterocyclyl and heterocyclylalkyl (except that R 1a1 can not be aminoalkyl or monoalkylaminoalkyl unless appropriately protected): Reaction Scheme 2 (D) (E) (F) (F) (F) Compounds of formula (D) and formula (E) are commercially available, e.g., from Aldrich Chemical Co. or Sigma Chemical Co., or may be made from methods known to those of ordinary skill in the art. ln general, compounds of formula (Ga) and formula (Gb) are prepared by first treating a compound of formula (D) in an anhydrous aprotic solvent, such as anhydrous ether, with an equimolar amount of a compound of formula (E) in an anhydrous aprotic solvent, such as anhydrous ether, over a period of time, for example, over a two hour period The resulting reaction mixture is stirred for about 2 to about 4 hours, preferably for about 3 hours, at ambient temperature The compound of formula (F) is isolated from the reaction mixture by standard isolation techniques, such as concentration of the product and purification by vacuum distillation To a solution of a strong reducing agent, such as lithium aluminum hydride, in an anhydrous polar aprotic solvent, such as tetrahydrofuran, is added the compound of formula (F) The resulting mixture is stirred at ambient temperature for about 30 minutes to about 2 hours, preferably for about 1 hour The mixture is then heated to reflux to complete the reaction Upon completion, the compound of formula (Ga) is isolated from the reaction mixture by standard isolation techniques, such as quenching by water and a mild base, followed by filtration Alternatively, to a solution of formula (F) in a polar protic solvent, such as absolute ethanol, is added a solid alkaline metal, such as sodium metal over a period of time, such as over a 3 hour period The resulting mixture is heated to reflux for about 2 to about 4 hours preferably for about 3 hours The compound of formula (Gb) is distilled from the reaction mixture by the addition of water to the reaction mixture The distillate is then treated with an aqueous acid, such as hydrochloric acid, to form the salt of the compound of formula (Gb) Compounds of formula (Ga) and formula (Gb) may then be treated with compounds of formula (B) in a manner similar to that described above in Reaction Scheme 1 to produce compounds of the invention wherein the relative orientation of the R 1a substituents is fixed C. Preparation of Compounds of Formula (la) The compounds of formula (la) are compounds of the invention and they are prepared as illustrated in the following Reaction Scheme 3 wherein each X is independently chloro or bromo, R 1a1 is one or more independently selected R 1a substituents as described above in the Summary of the Invention for compounds of formula (la) (except that R 1a1 can not contain a primary or secondary amine unless appropriately protected); R , R and R are as described in the Summary of the Invention for compounds of formula (la) (except that R 4 and R 5 can not contain a primary or secondary amine unless adequately protected); and R 3a is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylaikyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkyiamino, cycioalkylaminoalkyl, (cycloalkylalkyl)amino, (cycloalkyalkyl)aminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino. dialkylamino, monoarylammo, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkyicarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)aminoalkyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amino, alkoxycarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidino, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl; and R 4 and R 5 are as described above in the Summary of the Invention: Reaction Scheme 3 (H) (J) (K) (B) (la) The compounds of formula (B), formula (H) and formula (J) are commercially available, for example, from Aldrich Chemical Co. or Sigma Chemical Co., or may be prepared according to methods known to those of ordinary skill in the art In general, compounds of formula (la) are prepared by the foregoing Reaction Scheme by first treating a compound of formula (H) in a polar solvent, such as methanol, with an equimolar amount of a compound of formula (J) in an anhydrous polar solvent, such as anhydrous ether. The resulting reaction mixture is stirred at ambient temperature for about 5 minutes to about 24 hours in the presence of an acid-scavenging base, such as tπethylamine The compound of formula (K) is then isolated from the reaction mixture by standard isolation techniques, such as organic phase extraction, evaporation of solvents and purification by flash column chromatography. The compound of formula (K) in an aprotic polar solvent, such as tetrahydrofuran, is treated with an excess molar amount of a compound of formula (B) in the presence of a mild base, such as tπethyiamine and, optionally, a catalytic amount of sodium iodide. The resulting mixture is stirred at ambient temperature for about 1 to 5 days, preferably for about 2 days The compound of formula (la) is then isolated from the reaction mixture by standard isolation techniques such as filtration, concentration of volatiles and purification by flash column chromatography. Alternatively, compounds of formula (Ga) and formula (Gb), as prepared above in Reaction Scheme 2, may be used in place of compounds of formula (H) in this Reaction Scheme to produce compounds of the invention wherein the relative orientation of the R 1a substituents is fixed. D. Preparation of Compounds of Formula (la) Compounds of formula (la) are compounds of the invention and they are prepared as illustrated in the following Reaction Scheme 4 wherein X is chloro, bromo or an activated ester, P 1 and P 2 are independently nitrogen-protecting groups, such as f-butoxycarbonyl (P 1 can also be hydrogen), R 1a , R 2 , R 4 and R 5 are as described above in the Summary of the Invention, R 1b is as described above in the Summary of the invention for compounds of formula (lc) and (Id), and R 3a is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfmylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylamino, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno, (cycloalkyalkyl)amιnoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaralkyiaminoaikyl, aikylcarbonylammo, (alkylcarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)aminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylaminocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylammocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl Reaction Scheme 4 (L) (M) (N) (0) Reaction Scheme 4 continued (la) Compounds of formula (L), formula (N), formula (P) and formula (J) are commercially available, for example, from Aldrich Chemical Co or Sigma Chemical Co , or may be prepared according to methods known to one of ordinary skill in the art Compounds of formula (L) wherein the R 1 substituent contains an un-protected hydroxy group may be protected with the appropriate oxygen-protecting group prior to the synthesis of the compound of formula (M) Removal of the protecting group may be performed as desired In general, the compounds of formula (la) are prepared by first esteπfying a compound of formula (L) by treating the compound with an excess molar amount of a lower alkanol, preferably methanol, in the presence of an acid, preferably hydrochloπde gas, at about 0°C to ambient temperature The resulting mixture is then stirred at about 0°C to reflux temperature preferably at ambient temperature, for about 4 hours to about 18 hours The mixture is then concentrated by removal of solvents to produce the compound of formula (M) To a solution of the compound of formula (M) in an organic solvent, such as methanol, at about 0°C to ambient temperature, is added an excess molar amount of a compound of formula (N), and then treated with a mild acid, such as acetic acid, and stirred at ambient temperature for about 2 hours to about 4 hours, preferably for about 3 hours, to form an intermediate imine The imine is then reduced in situ by treatment with a reducing agent, such as sodium cyanoborohydπde, to produce a compound of formula (O), which is isolated from the reaction mixture by standard isolation techniques, such as filtration and purification by flash column chromatography To a solution of a compound of formula (P) in a polar aprotic solvent, such as anhydrous tetrahydrofuran, is added an acid scavenging mild base, such as Λ/-methylmorpholιne, followed by the addition of an acid coupling reagent, such as isobutylchloroformate The resulting mixture is stirred at about 0°C to ambient temperature for about 15 minutes to about 2 hours, preferably for about 15 minutes at 0°C and then for about an hour at ambient temperature, to form an intermediate active ester of the compound of formula (P) The intermediate is then treated in situ with a compound of formula (O) in anhydrous polar aprotic solvent, such as anhydrous tetrahydrofuran and the resulting mixture is stirred at ambient temperature for about 10 hours to about 24 hours, preferab'y for about 15 hours The compound of formula (Q) is isolated from the reaction mixture by standard isolation techniques, such as concentration, organic phase separation and purification by flash column chromatography The compound of formula (Q) in an aprotic solvent, such as methylene chloride, at about 0°C, is then treated with a strong organic acid, such as tπfluoroacetic acid for a period of about 2 to about 4 hours, preferably for about 2 hours, to remove the protecting group on the nitrogen atom, followed by spontaneous cyclization to form the compound of formula (R), which is isolated from the reaction mixture by standard isolation techniques, such as neutralization with a mild base, filtration and concentration The compound of formula (R) in an anhydrous polar aprotic solvent, such as anhydrous tetrahydrofuran, at about 0°C is treated with a strong reducing agent, such as lithium aluminum hydride The resulting mixture is then heated to reflux for about 12 hours to about 24 hours, preferably for about 15 hours The mixture is then cooled to ambient temperature and the reaction quenched with water, followed by aqeous base, preferably aqueous potassium hydroxide The resulting mixture is allowed to stir at ambient temperature for about 30 minutes to an hour The compound of formula (S) is then isolated from the reaction mixture by filtration and concentration The compound of formula (S) in a polar aprotic solvent, such as methylene chloride, in the presence of excess amount of an acid scavenging base, such as tπethyiamine, is added a slighly excess molar amount of a compound of formula (J) in a polar aprotic solvent, such as methylene chloride The resulting mixture is stirred at ambient temperature for about 15 minutes to about 1 hour, preferably for about 15 minutes The compound of formula (la) is then isolated from the reaction mixture by standard isolation techniques, such as extraction, concentration and flash column chromatography E. Preparation of Compounds of Formula (lb) Compounds of formula (lb) are compounds of the invention and are prepared as illustrated below in Reaction Scheme 5 where X is chloro or bromo, R 1 is as described above in the Summary of the Invention for compounds of formula (lc) and formula (Id), and R 2 is as described above in the Summary of the invention for compounds of formula (lb), R 3a is one or more substituents independently selected from the group consisting of hydrogen, halo, alkyl, alkoxy, aryloxy, haloalkyl, formyl, nitro, cyano aralkoxy, haloalkoxy, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, cycioalkylaminoalkyl, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, carboxyalkyl alkoxycarbonylalkyl, aryioxycarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, arylsulfonyl, hydroxyalkoxy, ammoalkoxy, (monoalkylamιno)aralkyl, aminoalkylamino, heterocyclylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylammo, alkylsulfonylammo, arylcarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, alkylsulfoπylaminoaikyl, (alkylsulfonyl)(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyclylammoalkyl, (hydroxyalkoxy)carbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (monoaikylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonylalkyl)aminocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, dialkylaminocarbonyloxyalkyl, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyθ(monoaryl)ureιdo, diarylureido, (haloalkylcarbonyl)ureιdo, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycmamido, (alkoxyalkylcarbonyi)glycιnamιdo, aminocarbonylglycinamido, (amιnocarbonyl)(alkyl)glycιπamιdo, (alkoxycarbonylalkylcarbonyl)(aikyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycmamido, (ary!carbonyl)(alkyl)glycιnamιdo, (monoaraikylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyl)(alkyl)glycιnamιdo, (monoaryiamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyl)(alkyl)glycιnamιdo, glycmamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, and R 4a is -O- or N(R 7a )- where R 7a is hydrogen, alkyl, aryl or aralkyl Reaction Scheme 5 (T) (lb) Compounds of formula (U) are commercially available, for example, from Aldrich Chemical Co. or Sigma Chemical Co., or may be prepared according to methods known to those of ordinary skill in the art. Compounds of formula (T) may be prepared according to the methods described herein for compounds of formula (C) or for compounds of formula (K), or by acylatmg the compounds of formula (C) as prepared herein by standard methods known to those of ordinary skill in the art. In general, the compounds of formula (lb) are prepared by the foregoing Reaction Scheme by first treating a compound of formula (T) in an anhydrous aprotic solvent, such as anhydrous dimethylformamide, with a slightly excess moiar amount of a compound of formula (U) in the presence of a mild base, such as potassium carbonate The resulting mixture is stirred at about 50°C for about 10 hours to about 24 hours, preferably for about 15 hours The compound of formula (lb) is then isolated from the reaction mixture by standard isolation techniques, such as extraction, filtration and precipitation F. Preparation of Compounds of Formula (lb) Compounds of formula (lb) may also be prepared as illustrated in the following Reaction Scheme 6 where X is chloro, bromo or an activated ester, P 1 is a nitrogen-protecting group, such as f-butoxycarbony; R 1b is as described above in the Summary of the Invention for compounds of formula (lc) and formula (Id), R 2a is as described above in the Summary of the Invention for R 2 in compounds of formula (lc) except that R 2a can not be formyl or formylalkyl, R 3a is one or more substituents independently selected from the group consisting of hydrogen hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno, (cycloalkyalkyl)amιnoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkylcarbonyl)(alkyOamιπo, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)ammoalkyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl. carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylaminocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl; and R 4a is -O- or -N(R 7a )- where R 7a is hydrogen, alkyl, aryl or aralkyl- Reaction Scheme 6 (V) (U) (W) (K) Compounds of formula (U) and formula (N) are commercially available, for example, from Aldrich Chemical Co. or Sigma Chemical Co., or may be prepared according to methods known to those of ordinary skill in the art. Compounds of formula (V) may be prepared according to the method described above for compounds of formula (K) in Reaction Scheme 3 In general, compounds of formula (lb) as prepared in the foregoing Reaction Scheme 6 are prepared by first treating a compound of formula (U) in an aprotic solvent, such as dimethylformamide, at about 0°C, with a strong base, such as potassium hexamethyldisilazide, to deprotonate the compound The resulting mixture is stirred for about 20 minutes to an hour, preferably for about 20 minutes, at about 0°C. An equimolar amount of a compound of formula (V) in an aprotic solvent, such as dimethylformamide is then added to the mixture and the resulting mixture is stirred at ambient temperature for about 1 to 24 hours, preferably for about 2 hours The compound of formula (W) is then isolated from the reaction mixture by standard isolation techniques, such as extraction and concentration. The P 1 protecting group is then removed from the compound of formula (W) to form a compound of formula (K) by standard amme-deprotectmg procedures, such as treating the compound of formula (W) with a strong acid, such as tπfluoroacetic acid To a solution of the compound of formula (K) in a polar solvent, such as methanol, at about 0°C to ambient temperature, was added an excess molar amount of a compound of formula (N), and then treated with a mild acid, such as acetic acid and stirred at ambient temperature for about 2 hours to about 4 hours, preferably for about 3 hours, to form an intermediate imine. The imine is then reduced in situ by treatment with a reducing agent, such as sodium cyanoborohydπde, to produce a compound of formula (lb), which is isolated from the reaction mixture by standard isolation techniques, such as filtration and purification by flash column chromatography. G. Preparation of Compounds of Formula (lb) Compounds of formula (lb) may also be prepared as illustrated in the following Reaction Scheme 7 where R 1b is as described above in the Summary of the Invention for compounds of formula (lc) and formula (Id); and R 2 is as described above in the Summary of the invention for the compounds of formula (lb); and R 3a is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfmylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno, (cycloalkyalkyl)amιnoaikyi, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, am o, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkylcarbonyl)(alkyl)amιno, alkylcarbonylammoalkyl, (alkyicarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl Reaction Scheme 7 (X) (Y) (C) (lb) Compounds of formula (X) are commercially available, for example, from Aldrich Chemical Co. or Sigma Chemical Co., or may be prepared acccordmg to methods known to those of ordinary skill in the art. Compounds of formula (C) may be prepared according to methods described herein. In general , the compounds of formula (lb) prepared by this Reaction Scheme are prepared by first treating a compound of formula (X) in an organic solvent, such as toluene, with phosgene for a period of time from about 1 hour to about 24 hours, preferably for about 2 hours, at reflux temperature to form the isocyanate of formula (Y), which is isolated from the reaction mixture by standard isolation techniques, such as concentration and filtration The compound of formula (Y) in an anhydrous aprotic polar solvent, such as tetrahydrofuran, is then treated with an equimolar amount of a compound of formula (C) The resulting mixture is stirred at ambient temperature for about 10 hours to about 48 hours, preferably for about 20 hours. The compound of formula (lb) is then isolated from the reaction mixture by standard isolation techniques, such as concentration and evaporation of solvents H. Preparation of Compounds of Formula (lc) Compounds of formula (lc) are compounds of the invention and are prepared as illustrated in the following Reaction Scheme 8 where Y is bromo, chloro or lodo; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 9 are as described above in the Summary of the Invention for compounds of formula (lc): Reaction Scheme 8 Compounds of formula (lb) are prepared as disclosed herein and compounds of formula R 9 Y are commercially available, for example, Aldrich Chemical Co. or Sigma Chemical Co., or may be prepared according to methods known to those of ordinary skill in the art. In general, compounds of formula (lc) are prepared by first treating a compound of formula (lb) in an non-polar organic solvent, such as toluene, with an excess molar amount of a compound of formula R 9 Y. The resulting mixture is stirred at ambient temperature for about 1 to 10 days, preferably for about 6 days. The compound of formula (lc) precipitates out of the solution as the quarternary salt and is isolated by standard isolation techniques such as filtration. The counteπon θ Y may be exchanged with other counteπons by methods known to those of ordinary skill in the art. In addition to the foregoing Reaction Schemes 1 through 8, other compounds of invention may be made by reactions known to one skilled in the art For example, a compound of formula (la), formula (lb), formula (lc), or formula (Id), or any appropriately substituted starting material or intermediate thereof, wherein at least one R 1a substituent or at least one R b substituent is selected from the group consisting of hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, hydroxyalkylthioalkyl, and hydroxyalkylammoalkyl, may be dissolved in an aprotic polar solvent, such as methylene chloride, in the presence of a mild acid scavenging base and then treated with a slightly excess molar amount of a sulfonyl halide, such as sulfonyl chloride, to form an intermediate compound containing a sulfonate leaving group. The compound may then be dissolved in an anhydrous aprotic solvent, such as dimethylformamide, and treated, in the presence of a mild base, with the appropriate nucleophilic reagent to form compounds of formula (la), formula (lb) or formula (lc), or any appropriately substituted starting material or intermediate thereof, wherein the R a substituent or the R 1b substituent (depending on the nucleophilic reagent utilized) may be selected from the group consisting of heterocyclylalkyl, monoalkylaminoalkyl, dialkylammoalkyl, cycloalkylammo, cyanoalkyl, (cycloalkylalkyl)amιnoalkyi, or hydroxyalkylthioalkyl. Alternatively, a compound of formula (la), formula (lc), formula (lc), or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contains a hydroxy group, such as hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, hydroxyalkylthioalkyl, and hydroxyalkylammoalkyl, may be treated with a mild oxidizing agent, such as oxalyl chloride, which is dissolved in an inert organic solvent, such as methylene chloride, to which DMSO is added over a period of time at about -60°C to about 0°C, preferably at about -50°C. The reaction mixture is stirred at about -60°C to about 0°C for about 15 minutes to about an hour, preferably for about 15 minutes, and then a mild base, such as tπethylamine, is added to the mixture The mixture is allowed to gradually warm to ambient temperature, at which point the oxidized compound (i.e., the corresponding aldehyde) of formula (la), formula (lb), or formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, is isolated from the reaction mixture by standard isolation techniques. Alternatively, a compound of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contains an aldehyde or a ketone group, such as formyl, alkylcarbonyl or alkylcarbonylalkyl, may be treated with the appropriate organometallic reagent, such as an organomagnesium or organolithium, under standard Grignard synthesis reaction conditions to form the corresponding hydroxy- substituted compounds. Alternatively, a compound of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contains a hydroxy group, such as hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, hydroxyalkylthioalkyl, and hydroxyalkylammoalkyl, in an anhydrous polar solvent, such as anhydrous ether, in the presence of a strong base, such as sodium hydride, may be treated with an alkyl halide, such as methyl iodide, at ambient temperatures, to form the corresponding alkoxy-substituted compounds Alternatively, a compound of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, wherein at least one R 1a substituent or at least one R 1b substituent is formyl or formylalkyl, may be reacted with a primary or secondary amine, under the reductive amination conditions as described above for the preparation of the compounds of formula (O) or the compounds of formula (lb) as prepared in Reaction Scheme 6 to form the corresponding compounds of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, wherein the R a substituent or the R 1b substituent is monoalkylaminoalkyl, dialkylammoalkyl, monoaraikylammoalkyl, or hydroxyalkylammoalkyl Alternatively, a compound of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contains an ester group, such as an alkoxycarbonyl, aryloxycarbonyl or aralkoxycarbonyl group, may be subjected to standard basic hydrolysis conditions, to form the corresponding compound of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contains an acid group, / e a carboxy group Alternatively, a compound of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, wherein R 6 is -C(O)- may be reduced to the corresponding compound of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, wherein R 6 is -CH 2 - by methods known to those of ordinary skill in the art, for example, by the method described above for compounds of formula (S) In addition, compounds of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, wherein R 6 is -C(O)- may be converted to a compound of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, wherein R 6 is -C(S)- by treatment with Lawesson's Reagent under standard conditions known to those of ordinary skill In addition, compounds of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contain an unoxidized sulfur atom may be oxidized with the appropriate sulfur oxidizing agent according to methods known to those skilled in the art, such as using hydrogen peroxide, to produce the corresponding compounds which contain a sulfinyl or a sulfonyl group in place thereof Alternatively, compounds of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contain a carboxy group can be converted to compounds containing the corresponding amide group by first converting the carboxy group into an activated ester or mixed anhydride using, for example isobutyi chloroformate in the presence of a mild base, such as tV-methylmorpholine, in an aprotic solvent, such as THF, and then treating the ester with the appropriately substituted primary or secondard amine in an aprotic solvent, such as THF Alternatively, compounds of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contain a cyano group can be converted to the compounds containing a hydroxyamidino group by reaction with the an hydroxyamme in a polar solvent, such as DMSO The hydroxyamme may be prepared in situ by first treating the hydrochloπde salt of the hydoxyamme with a base, such as tπethylamine Alternatively, of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contain a hydroxy group may be converted to the compounds containing the corresponding azide group by treating the compound with tπphenyiphosphine and an alkyl azodicarboxylate, for example diethylazodicarboxylate, in an aprotic solvent, such as THF, and then displacing the activated oxygen so formed with an azide source, such as diphenylphosphorylazide, in an aprotic solvent, such as THF Alternatively, compounds of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contain a -NH 2 group or a -R a -NH 2 group may be converted to compounds containing a corresponding -R a -N(H)- C(0)- group by reacting the compound with appropriately substituted acid halide under standard acylation conditions Alternatively, compounds of formula (la), formula (lb), formula (lc) or formula (id), or any appropriately substituted starting material or intermediate thereof, which contain a acid halide group (-C(O)-X where X is halo) or an activated ester group can be converted to compounds containing the corresponding -C(0)-N(H)- group by reacting the compound with the appropriately substituted primary or secondardy amine under standard acylation or amide bond formation conditions Alternatively, compounds of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contains an primary or secondary amine group can be converted to compounds containing the corresponding aminoalkyl group in a manner similar to the conversion of formula (M) to formula (O) in Reaction Scheme 4 In particular, the amine is reacted with an appropriately substituted aldehyde to form the intermediate imine, which is then reduced by treatment with an appropriate reducing agent, such as sodium cyanoborohydπde Alternatively, compounds of formula (la), formula (lb), formula (lc) or formula (Id), or any appropriately substituted starting material or intermediate thereof, which contain a primary or secondary amine can be converted to the compounds containing the corresponding ureido group by reacting the compound with phosgene in a manner similar to Reaction Scheme 7 above (in an aprotic solvent) to form the corresponding isocyanate, which is then reacted witn the appropriately substituted primary or secondary amine In addition, all compounds of the invention that exist in free base form or free acid form may be converted to their pharmaceutically acceptable salts by treatment with the appropriate inorganic or organic acid, or by the appropriate inorganic or organic base Salts of the compounds of the invention can also be converted to the free base form or to the free acid form or to another salt by methods known to those skilled in the art The following specific Preparations and Examples are provided as a guide to assist in the practice of the invention, and are not intended as a limitation on the scope of the invention ln the following Preparation and Examples, all NMR data refers to 1 H NMR spectrum data and is given in the format of "(multiplicity, number of hydrogens)". The yield of each of the reactions described herein is expressed as a percentage of the theoretical yield. PREPARATION 1 Compounds of Formula (C) A. To a solution of 2-methylpiperazιne (0.10 g, 1 mmol) in CH 2 CI 2 (2 mL) was added 4-fluorobenzyl bromide (0.125 mL, 1 mmol). The resultant mixture was stirred at ambient temperature. After 15 hours, the mixture was concentrated in vacuo to afford a solid This solid was dissolved in CH 2 CI 2 and washed sequentially with water, aqueous NaHC0 3 solution, then brine. The organic layer was dried over MgS0 , filtered, and concentrated to an oil Purification by flash column chromatography afforded 0.025 g (12% yield) of 1-(4- fluorobenzyl)-3-methylpιperazιne, a compound of formula (C), as a colorless oil; NMR (CDCI 3 ) 7.3 (m, 2), 7.0 (m, 2), 3.4 (s, 2), 3.0-2.6 (m, 5), 2.0 (br s, 2), 1.6 (t, 1 ), 1.0 (d, 3) ppm. B. In a similar manner, the following compounds of formula (C) were made (2R,5S)-1 -(chloro )acetyl-4-(4-fluorobenzyl)-2,5-dιmethylpιperazιne-1-(4-fluorobenzyl)pιperazιne, (frans)-1-(4-fluorobenzyl)-2,5-dιmethyipιperazιne; (cis )-1-(4-fluorobenzyl)-2,3-dιmethylpιperazιne; (frans)-1 -(4-fluorobenzyl)-2,3-dιmethylpιperazιne; and (cis H -(4-fluorobenzyl)-3,5-dιmethylpιperazιne C. In a similar manner, other compounds of formula (C) are made. PREPARATION 2 Compounds of Formula (F) A. To a solution of ethylene diamine (13 g, 216 mmol) in anhydrous ether (600 mL) was added 2,3-butanedione (18.6 g, 216 mmol, in 200 mL anhydrous ether) dropwise over 2 hours. The resulting mixture was stirred at ambient temperature. After 3 hours, the clear solution was concentrated in vacuo to afford a brown oil. Purification by vacuum distillation afforded 16.6 g (70% yield) of 5,6-dιmethyl-2,3-dihydropyrazιne, a compound of formula (F), as clear, yellow oil; b.p. 60°C /16 mm Hg, NMR (CDCI 3 ) 3.3 (br s, 4), 2.1 (s, 6) ppm. B In a similar manner, other compounds of formula (F) are made. PREPARATION 3 Compounds of formula (Ga) A To a solution of lithium aluminum hydride (0 36 g, 10 mmol) in anhydrous tetrahydrofuran (50 mL) was carefully added 5,6-dιmethyl-2,3-dιhydropyrazιne (1 0 g, 9 mmol, in 10 mL of anhydrous tetrahydrofuran) The resulting mixture was stirred at ambient temperature for 1 hour, then heated to reflux After the reaction was completed, as determined by thin layer chromatographic analysis of reaction mixture, the reaction mixture was cooled to ambient temperature and quenched by sequential addition of 0 4 mL of water, 0 4 mL of 15% aqueous NaOH solution, then 1 2 mL of water After brief shaking, the mixture was filtered through a fritted funnel Filtrate was concentrated in vacuo to 0 92 g (90% yield) of (c/s)-2,3- dimethylpiperazme, a compound of formula (Ga), as clear, yellow oil, NMR (CDCI 3 ) 2 7 (m, 4) 2 5 (m, 2), 0 9 (d, 6) ppm B In a similar manner, other compounds of formula (Ga) are made PREPARATION 4 Compounds of formula (Gb) A To a solution of 5,6-dιmethyl-2,3-dιhydropyrazιne (2 3 g, 21 mmol) in absolute ethanol (60 mL) was added sodium metal (6 5 g, 280 mmol) in small portions over a 3 hour period The resulting mixture was heated to reflux After 3 hours at reflux, the product was distilled from the mixture while 200 mL of water was added gradually to reaction vessel The distillate was treated with 1 N aqueous HCI solution and concentrated in vacuo to afford a semi- solid Titration with acetone afforded 0 78 g (20% yield) of (frans)-2,3-dιmethyipιperazιne, a compound of formula (Gb), as an orange solid, NMR (DMSO-d 6 ) 9 8 (br s, 4), 3 5-3 2 (m, 6), 1 2 (s, 6) ppm B In a similar manner, other compounds of formula (Gb) are made PREPARATION 5 Compounds of Formula (K) A To a solution of (c/s)-2,6-dιmethylpιperazιne (0 115 g, 1 1 mmol) in methanol (35 mL) was added 4-chlorophenoxyacetyl chloride (0.205 g, 1 0 mmol, in solution of 6 mL of anhydrous ether). The resulting mixture was stirred at ambient temperature for 10 minutes and then tπethylamine (0.10 mL, 0.72 mmol) was added. After 30 minutes, the mixture was concentrated in vacuo to afford an oily residue. This was taken up in ether and washed with saturated aqueous NaHC0 3 solution, then brine. The organic layer was separated, dried over MgS0 4 , filtered and concentrated in vacuo to afford an oil. Purification by flash column chromatography afforded 0.202 g (80% yield) of (c/s)-1-((4-chlorophenoxy)methyl)carbonyl-3,5- dimethylpiperazine, a compound of formula (K), as a clear, colorless oil; NMR (CDCI 3 ) 7.3 (d, 2), 6.9 (d, 2), 4.7 (d,1 ), 4.6 (d,1 ), 4.4 (d,1 ), 3.8 (d,1 ), 2.7 (m, 3), 2.2 (t, 1 ), 1.1 (m, 6) ppm. B. In a similar manner, the following compounds of formula (I) were made: (3S,5S)-1 -((4-chlorophenoxy)methyl)carbonyl-3,5-dιmethylpιperazιne; and (3f?,5f?)-1-((4-chlorophenoxy)methyl)carbonyl-3,5-dιmethylpιperazιne. C. In a similar manner, other compounds of formula (K) are made. PREPARATION 6 Compounds of Formula (M) A. A solution of (2f?)-3-benzyloxy-2-(Λ/-(f-butoxycarbonyl)amιno)propanoιc acid (23 g, 78 mmol, [α] D -4 4° (c = 2, H 2 0)) in methanol (250 mL) was cooled to 0°C and HCI (g) bubbled into the solution until saturated. The resulting mixture was stirred at ambient temperature for 17 hours and then concentrated in vacuo to afford 17 g (100% yield) of (2R)-3- benzyloxy-2-amιnopropanoιc acid methyl ester, a compound of formula (M), as a white solid. NMR (DMSO-d 6 ) 8.7 (br s, 3), 7.4-7.3 (m, 5), 4.5 (q, 2), 4.4 (br s, 1 ), 3.8 (s, 2), 3.7 (s, 3) ppm B. In a similar manner, other compounds of formula (M) are made. PREPARATION 7 Compounds of Formula (O) A. A solution of (2R)-3-benzyloxy-2-amιnopropanoιc acid methyl ester (19 g, 78 mmol) in methanol (350 mL) under N 2 was cooled to 0°C and acetic acid (2 g, pH 2) was added, followed by the addition of 4-fluorobenzaldehyde, a compound of formula (N) (12.5 mL, 117 mmol) and sodium cyanoborohydπde (7.3 g, 1 17 mmol) and 3 A molecular sieves (15 g) The resulting mixture was stirred at ambient temperature for 3 hours, then filtered through Celite (MeOH). The filtrate was concentrated in vacuo to afford a clear liquid. This was taken up in ethyl acetate and washed sequentially with 10% aqueous Na 2 C0 3 solution, water, then bπne The organic phase was then dried over MgS0 , filtered, and concentrated in vacuo Purification by flash column chromatography on silica gel afforded 14 7 g (60% yield) of (2 ?)-3- benzyloxy-2-(Λ/-(4-fluorobenzyl)amιno)propanoιc acid methyl ester, a compound of formula (O), as a clear, colorless oil, NMR (CDCI 3 ) 7 4-7 2 (m, 7), 7 0 (dd, 2), 4 5 (d, 2), 3 9-3 5 (m, 8) ppm, MS (LSIMS) 317 B In a similar manner, the following compounds of formula (O) were made (2R)-2-(Λ/-(4-fluorobenzyl)amιno)propanoιc acid methyl ester, (2S)-2-(Λ -(4-fluorobenzyl)amιno)propanoιc acid methyl ester, (2R)-2-(Λ/-(4-fluorobenzyl)amιno)-4-methylthιobutanoιc acid methyl ester, (2f?)-2-(Λ -(4-fluorobenzyl)amιno)-3-methoxypropanoιc acid methyl ester, (2 )-2-(Λ -(4-fluorobenzyl)amιno)-3-((2-hydroxyethyl)thιo)propanoιc acid methyl ester, and (2f?)-2-(Λ -(4-fluorobenzyi)amιno)-3-methylbutanoιc acid methyl ester C In a similar manner, the following compounds of formula (O) are made (2S)-2-(Λ/-(4-fluorobenzyl)amιno)-4-methylthιobutanoιc acid methyl ester, (2S)-2-(Λ.-(4-fluorobenzyl)ammo)-3-methoxypropanoιc acid methyl ester, (2S)-2(Λ/-(4-fiuorobenzyl)amιno)-3-((2-hydroxyethyl)thιo)propanoιc acid methyl ester, (2S)-2-(Λ/-(4-fluorobenzyl)amιno)-3-methylbutanoιc acid methyl ester, (2R)-2-(Λ/-(4-fluorobenzyl)amιno)butanoιc acid ethyl ester, (2S)-2-(Λ/-(4-fluorobenzyl)amιno)butanoιc acid ethyl ester, (2R)-2-(/V-(4-chlorobenzyl)amιno)butanoιc acid methyl ester, (2S)-2-(Λ/-(4-chlorobenzyl)amιno)butanoιc acid methyl ester, (2R)-2-(Λ/-(4-chlorobenzyl)amιno)-4-methylthιobutanoιc acid methyl ester, (2R)-2-(Λ/-(4-chlorobenzyl)amιno)-3-methoxypropanoιc acid methyl ester, (2ft)-2-(/V-(4-chlorobenzyl)amιno)-3-((2-hydroxyethyl)thιo)propanoιc acid methyl ester, and (2R)-2-(Λ/-(4-chlorobenzyl)amιno)-3-methylbutanoιc acid methyl ester D In a similar manner, other compounds of formula (O) are made PREPARATION 8 Compounds of Formula (Q) A. To a solution of -V-f-butoxycarbonyl-D-aianme (5.6 g, 30 mmol, [ ] D +23° (c=2, CH 3 C0 2 H)) in anhydrous tetrahydrofuran (150 mL) under N 2 at 0°C was added N- methylmorpholme (3.0 g, 30 mmol), followed by the addition of isobutylchloroformate (3 7 mL, 30 mmol), resulting in the formation of a white solid The resulting suspension was stirred at 0°C for 15 minutes, and then at ambient temperature for 1 hour A solution of (2 )-3- benzyloxy-2-(Λ/-(4-fluorobenzyl)-amιno)propanoιc acid methyl ester (7 5 g, 24 mmol, in 50 mL of anhydrous tetrahydrofuran) was added to the mixture and the resulting mixture was stirred at ambient temperature After 15 hours, the mixture was filtered through Celite (tetrahydrofuran) The filtrate was concentrated in vacuo to afford a yellow liquid, which was dissolved in ethyl acetate, washed with water and then with brine The organic phase was separated then dried over MgS0 , filtered, and concentrated in vacuo Purification by flash column chromatography on silica gel afforded 7 3 g (63% yield) of (2R)-3-benzyloxy-2-(Λ/-(4-fluorobenzyl)-Λ/-(((1 S)-1 -(f- butoxy-carbonylamιno)ethyl)carbonyl)amιno)propanoιc acid methyl ester, a compound of formula (Q), as a clear oil, NMR (CDCI 3 ) 7 4-7 2 (m, 7), 7 0 (dd, 2), 5 3 (d, 2), 4 9-4, 3 (m, 5) 4 1-3 7 (m, 4), 1 6 (s, 9), 1 0 (d, 3) ppm B In a similar manner, the following compounds of formula (Q) were made (2R)-2-(Λ/-(4-fluorobenzyl)-Λ/-(((1 S)-1-(f-butoxycarbonylamιno)ethyl)carbonyl)amιno)propanoιc acid methyl ester, (2S)-2-(Λ/-(4-fluorobenzyl)-Λ/-(((1 S)-1-(f-butoxycarbonylamιno)ethyl)carbonyl)amιno)propanoιc acid methyl ester, (2R)-2-(Λ -(4-fluorobenzyl)-/V-(((1 R)-1-(f-butoxycarbonylamιno)ethyl)carbonyl)amιno)propanoιc acid methyl ester, (2S)-2-(Λ -(4-fluorobenzyl)--V-(((1R)-1-(f-butoxycarbonylamιno)ethyl)carbonyl)amιno)propanoιc acid methyl ester; (2R)-2-(Λ/-(4-fluorobenzyl)-Λ/-(((1 S)-1-(f-butoxycarbonylamιno)ethyl)carbony0amιno)- 4-methylthιobutanoιc acid methyl ester, (2R)-2-(Λ/-(4-fluorobenzyl)-Λ/-(((1 S)-1 -(f-butoxycarbonylamιno)ethyl)carbonyl)amιno)- 3-methoxypropanoιc acid methyl ester; (2R)-2-(Λ/-(4-fluorobenzyl)-V-(((1 S)-' , -(f-butoxycarbonylamιno)ethyl)carbonyl)amιno)- 3-((2-hydroxyethyl)thιo)propanoιc acid methyl ester, (2R)-2-(Λ/-(4-fluorobenzyl)-Λ/-(((1 S)-1-(f-butoxycarbonylamιno)ethyl)carbonyl)amιno)- 3-methylbutanoιc acid methyl ester, and (2R)-2-(Λ/-(4-fluorobenzyl)-iV-(((1 S)-1-(f-butoxycarbonylamιno)-2-(ethoxycarbonyl)ethyl)- carbonyl)amιno)propanoιc acid methyl ester C In a similar manner, other compounds of formula (Q) are made PREPARATION 9 Compounds of Formula (R) A To a solution of (2R)-3-benzyloxy-2-(Λ/-(4-fluorobenzyl)-Λ/-(((1 S)-1-(f-butoxy- carboπylamιno)ethyl)carbonyi)amιno)propanoιc acid methyl ester (2 0 g, 4 mmol) in CH 2 CI 2 (25 mL) was cooled to 0°C and tπfluoroacetic acid (25 mL) was added dropwise over 2 hours At the end of the addition, the ice bath was removed and the mixture was stirred at ambient temperature After 2 hours, the mixture was concentrated in vacuo The residual yellow oil was taken up in ethyl acetate and washed with 1 N aqueous NaHC0 3 solution The organic layer was separated then dried over MgS0 , filtered, and concentrated in vacuo to afford 1 2 g (83% yield) of (2R,5S)-1-(4-fluorobenzyl)-2-(benzyloxy)methyl-5-methylpιperazιne-3,6-dιone, a compound of formula (R), as a clear oil, NMR (CDCI 3 ) 7 4-7 2 (m, 7), 7 0 (dd, 2), 5 0 (d, 1 ) 4 5- 4 0 (m, 4), 3 9-3.5 (m, 4), 1.5 (d, 3) ppm, MS (LSIMS) 356 B In a similar manner, the following compounds of formula (R) were made (2R,5S)-1-(4-fluorobenzyl)-2,5-dιmethylpιperazιne-3,6-dιone, (2S,5S)-1-(4-fluorobenzyl)-2,5-dιmethylpιperazιne-3,6-dιone, (2R,5R)-1 -(4-fluorobenzyl)-2,5-dιmethylpιperazme-3,6-dιone, (2S,5R)-1-(4-fluorobenzyl)-2,5-dιmethyipιperazιne-3,6-dιone, (2R,5S)-1-(4-fiuorobenzyl)-2-(2-methylthιoethyl)-5-methyipιperazιne-3,6-dιone, (2 5S)-1-(4-fluorobenzyl)-2-(methoxymethyl)-5-methylpιperazιne-3,6-dιone, (2R,5S)-1-(4-fluorobenzyl)-2-((2-hydroxyethyl)thιomethyl)-5-methylpιperazιne-3,6-dιone, (2R,5S)-1-(4-fluorobenzyl)-2-(1-methylethyl)-5-methylpιperazιne-3,6-dιone, and (2R,5S)-1-(4-fluorobenzyl)-2-methyl-5-(ethoxycarbonyl)methylpιperazιne-3,6-dιone. C. In a similar manner, other compounds of formula (R) are made: PREPARATION 10 Compounds of Formula (S) A. To a suspension of (2 5S)-1-(4-fluorobenzyl)-2-(hydroxy)methyl-5-methyl- piperazine-3,6-dione (2.0 g, 7.5 mmol) in anhydrous tetrahydrofuran (50 mL) under N 2 at 0°C was carefully added lithium aluminum hydride (2.2 g, 60 mmol). The resulting suspension was heated to reflux. After 15 hours, the mixture was cooled to ambient temperature and carefully quenched with water (2 mL), then 1 N aqueous KOH solution (6 mL). The resulting suspension was stirred at ambient temperature for 30 minutes, then filtered through Celite (ethyl acetate). The filtrate was concentrated in vacuo to afford 1.6 g (90% yield) of (2R,5S)-1-(4-fluorobenzyl)- 2-(hydroxy)methyl-5-methylpiperazine, a compound of formula (S), as a white solid; NMR (CDCI 3 ) 7.3 (dd, 2), 7.0 (dd, 2), 4.2-4.0 (m, 2), 3.5 (d, 1 ) 3.0 (m, 2), 2.7 (m, 2), 1.7 (m, 1 ), 1.0 (d, 3). B. In a similar manner, the following compounds of formula (S) were made: (2R,5S)-1-(4-fluorobenzyl)-2,5-dimethylpiperazine; (2S,5S)-1-(4-fluorobenzyl)-2,5-dimethylpiperazine; (2R,5R)-1-(4-fluorobenzyl)-2,5-dimethylpiperazine; (2S,5R)-1-(4-fluorobenzyl)-2,5-dimethyipiperazine; (2R,5S)-1-(4-fluorobenzyl)-2-(2-methylthioethyl)-5-methylpiperazine; (2R,5S)-1-(4-fluorobenzyl)-2-(methoxymethyl)-5-methylpiperazine; (2R,5S)-1-(4-fluorobenzyl)-2-((2-hydroxyethyl)thiomethyl)-5-methylpiperazine; (2R,5S)-1-(4-fluorobenzyl)-2-(1-methylethyl)-5-methylpiperazine; and (2R,5S)-1-(4-fluorobenzyl)-2-methyl-5-(ethoxycarbonyl)methylpiperazine. C. In a similar manner, other compounds of formula (S) are made. PREPARATION 11 Compounds of formula (W) A. To a solution of 3,4,5-trimethoxyphenol (2.8 g, 15 mmol) in DMF (60 mL) at 0°C was added potassium hexamethyldisilazide (32 mL, 16 mmol, 0.5 M solution in toluene). The resulting mixture was stirred at 0°C. After 20 minutes, 1 -(chloro )acetyl-4-(f-butoxycarbonyl)- piperazine (4.6 g, 15 mmol, in 15 mL of DMF) was added and the mixture stirred at ambient temperature. After 2 hours the mixture was poured into water and extracted with ethyl acetate. The organic layer was separated, dried over MgS0 , filtered and concentrated in vacuo to afford 6.5 g (100% yield) of 1-((3,4,5-trimethoxyphenoxy)methyl)carbonyl-4-(f- butoxycarbonyOpiperazine, a compound of formula (W), as a yellow solid; NMR (CDCI 3 ) 7.2 (m, 2), 4.6 (s, 2), 3.8 (m, 9), 3.6 (m, 4), 3.4 (m, 4), 1.5 (s, 9) ppm. B. In a similar manner, the following compounds of formula (W) were made: 1-((4-chiorophenyl)methyl)carbonyl-4-(f-butoxycarbonyl)piperazine; (3R)-1 -((4-chlorophenyl)methyl)carbonyl-3-methyl-4-(f-butoxycarbonyl)piperazine; (3S)-1-((4-chlorophenyl)methyl)carbonyl-3-methyl-4-(f-butoxycarbonyl)piperazine; and 1-((4-chlorophenyl)methyl)carbonyl-3-(2-((((4-chlorophenoxy)methyl)carbonyi)oxy)ethyl)- 4-(f-butoxycarbonyl)piperazine. C. In a similar manner, other compounds of formula (W) are made. PREPARATION 12 Compounds of formula (Y) A. To a solution of 4-chlorobenzylamine (0.50 g, 3.5 mmol) in toluene (15 mL) was added phosgene (7.3 mL, 14 mmol, 1.93 M solution in toluene). The resulting mixture was stirred at ambient temperature for 15 minutes, then heated to reflux. After 2 hours at reflux, the mixture was cooled to ambient temperature and concentrated in vacuo to afford 0.70 g (100% yield) of 4-chlorobenzylisocyanate, a compound of formula (Y), as a yellow liquid; NMR (CDCI 3 ) 7.4-7.2 (m, 4), 4.4 (m, 2) ppm. B. In a similar manner, other compounds of formula (Y) are made. EXAMPLE 1 Compounds of Formula (la) and Formula (lb) A. To a solution of (2R,5S)-1-(4-fluorobenzyl)-2-(hydroxy)methyl-5-methylpiperazιne (1.6 g, 6.7 mmol) in CH 2 CI 2 (30 mL) was added triethylamine (excess) and 4- chlorophenoxyacetyl chloride (1.5 g, 7.4 mmol, dropwise in 10 mL solution of CH 2 CI 2 ). The resultant mixture was stirred at ambient temperature. After 20 minutes, analysis by analytical TLC showed complete consumption of starting material had occurred. The mixture was concentrated of volatiles in vacuo and the residue taken up in CH 2 CI 2 . This was washed with saturated aqueous NaHC0 3 solution, then water, then brine, dried over MgS0 , filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel afforded 2.16 g (79% yield) of (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5- ((hydroxy)methyθpιperazιne, as a solid yellow foam: NMR (DMSO-d 6 ) 7.7 (br s, 2), 7.3 (m, 4), 6.9 (d, 2), 5.0-4.2 (m, 5), 4.0-3.2 (m, 7), 1.2 (m, 3) ppm; MS (LSIMS) 406. B. In a similar manner, other compounds of formula (la) were made: 1-((4-chlorophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)-5-methylpιperazιne, trifluoroacetic acid salt; NMR (DMSO-d 6 ) 7.6 (m, 2), 7.3 (m, 4), 6 9 (m, 2), 5.0-3 8 (m, 6), 3.5-2.8 (m, 5). 1 4 (m, 3) ppm, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-ethylpιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-methylpιperazιne; 4-benzyl-1-((4-chlorophenoxy)methyl)carbonyl-2-phenylpιperazine; (2f?)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(1-methylethyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carboπyl-2-(methoxymethyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-ethylpιperazιne-3-one; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-ethylpιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 4 4 (m, 1 ), 3 7 (m, 1 ), 3.4 (m, 2), 2 8 (m, 2), 2.0-1.7 (m, 5), 0.9 (m, 3) ppm; (2S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-methylpropyl)pιperazιne, (frat7s)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,5-dιmethylpιperazιne, NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (m, 2), 4.2 (m, 1 ), 3.6-3.0 (m, 5), 2 7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (2R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-benzylpιperazιne; 4-(benzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-phenyipιperazιne-3-one; 4-(4-fluorobenzyl)-1-((4-chiorophenoxy)methyl)carbonyl-2-(2-hydroxyethyl)pιperazιne, NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.7 (m, 3), 3.8-3.2 (m,5), 2.8 (m, 2), 2.2 (m, 2), 2.0 (m, 2), 1.7 (m, 2) ppm; (c/s)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,6-dιmethylpιperazιne; NMR (DMSO-d 6 ) 7.6 (m, 2), 7.3 ( , 4), 6.9 (d, 2), 4.8 (m, 3), 4.4 (m, 3), 3.3 (d, 2), 3.0 (m, 2), 1.4 (m, 6) ppm; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(1-methyipropyl)pιperazιne; 4-(4-fluorobenzyi)-1-((4-chlorophenoxy)methyl)carbonyl-2-methylpιperazιne, hydrochioπde salt, (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,5-dιmethylpιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (m, 2), 4.2 (m, 1 ), 3.6-3.0 (m, 5), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (2R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-methylpropyl)pιperazιne, 4-(4-fluorobenzyl)-1 -((4-chlorophenoxy)methyl)carbonyl-2-(butyl)pιperazιne, (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-hydroxyethyl)- 5-methylpιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (m, 2), 4.6 (m, 3), 3.5 (m, 5), 3.2 (dt, 1 ), 3.0 (m, 1 ), 2.8 (dd, 1 ), 2.2 (m, 2), 1.6 (m, 2), 1.0 (d, 3) ppm; (2S,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,5-dimethylpιperazιne, NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (m, 2), 4.2 (m, 1 ), 3.6-3.0 (m, 5), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (2S,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,5-dιmethylpιperazιne, hydrochoπde salt; NMR (DMSO-d 6 ) 7.6 (m, 2), 7.2 (m, 4), 6.9 (d, 2), 4 8 (m, 2), 4 4 (m, 1 ), 4.1 (t, 1 ), 3.9-2.9 (m, 6), 1.5-1.2 (m, 6) ppm; (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,5-dιmethylpιperazιne, hydrochloπde salt; NMR (DMSO-d 6 ) 7.6 (m, 2), 7.2 (m, 4), 6.9 (d, 2), 4.8 (m, 2), 4 4 (m, 1 ), 4.1 (t, 1 ), 3.9-2.9 (m, 6), 1.5-1.2 (m, 6) ppm; 4-(4-fluorobenzy0-1-((4-chlorophenoxy)methyl)carbonyl-2-(1 ,1-dιmethylethyi)pιperazιne, (2S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-methylpropyl)pιperazιne, (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-(((4-chlorophenoxy)- methyl)carbonyl)oxy)ethyl-5-methylpιperazιne; NMR (CDCI 3 ) 7.2 (m, 6), 7.0 (m, 2), 6 8 (m, 4), 4 7-4.0 (m, 7), 3.6 (m, 2), 3.4 (m, 1 ), 3.1 (m, 1 ), 2.6 (m, 1 ), 2.3 (m, 2), 2.0 (m, 2), 1.0 (d, 3) ppm; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(methoxycarbonyl)methylpιperazιne, (2S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-propylpιperazιne; (c/s -4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,3-dιmethylpιperazιne, hydrochloride salt; NMR (DMSO-d 6 ) 7.6 (m, 2), 7.2 (m, 4), 6.9 (m, 2), 5.0-4 1 (m, 6), 3.5- 2.9 (m, 4), 1.5-1.2 (m, 6) ppm; (2R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-benzyipιperazιne; (2R)-4-(4-fluorobenzy -1-((4-chlorophenoxy)methyl)carbonyl-2-propyipιperazιne, NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (m, 2), 4.4 (m, 1 ), 3.7 (m, 1 ), 3.4 (m, 2), 3.0 (m, 1 ), 2.7 (m,2), 2.0-1.6 (m, 4), 1.2 (m, 2), 0.9 (m, 3) ppm ; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(ethoxycarbonyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxyethyl)pιperazιne, NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6 9 (dd, 2), 4 7 (d, 2), 4.0-3.4 (m, 8), 2.8 (m, 2), 2 3 (m, 1 ), 1.8 (m, 3) ppm, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(hydroxymethyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (t, 2), 4.7 (d, 2), 3.9-3.2 (m, 7), 2.8-2.2 (m, 4) ppm; (2S)-4-(4-fluorobenzyl)-1 -((4-chlorophenoxy)methyl)carbonyl-2-butylpιperazιne; (2R,6R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,6-dιmethylpιperazιne, hydrochloride salt; NMR (CDCI 3 ) 7 7 (br s, 2), 7 2 (m, 4), 6 8 (d, 2), 4.6 (s, 2), 4 4 (m, 3), 3.9 (m, 1 ), 3.5 (m, 1 ), 3.2 (m, 1 ), 2.8 (m, 2), 1.6 (s, 6) ppm, (2S,6S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyi)carbonyl-2,6-dιmethylpιperazιne, hydrochloride salt, NMR (CDCI 3 ) 7 7 (br s, 2), 7.2 (m, 4), 6.8 (d, 2), 4 6 (s, 2), 4 4 (m, 3), 3.9 (m, 1 ), 3.5 (m, 1 ), 3.2 (m, 1 ), 2.8 (m, 2), 1 6 (s, 6) ppm; 4-(4-fluorobenzyl)-1-(((4-chlorophenoxy)methyl)carbonyl)spιro[cyclopropane-1 ,2'-pιperazιne], NMR (CDCI 3 ) 7.3 (m, 4), 7.0-6.8 (m, 4), 4.6 (m, 4), 2.8 (m, 2), 2.2-1.6 (m, 4) ppm, 4-(4-fluorobenzy0-1-((4-chlorophenoxy)methyl)carboπyl-2-(trifluoromethyl)pιperazιne, (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(2- methylthio)ethylpιperazιne, hydrochloride salt; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-((((4-chlorophenoxy)- methyl)carbonyl)oxy)methylpιperazιne; (2S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-propylpιperazιne, NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 3.8 (m, 2), 3.4 (m, 2), 3.2 ( , 2), 2.6 (m, 1), 2.4 (m, 1 ), 2.2 (m, 1 ), 1.6-1.3 (m, 4), 0.9 (m, 3) ppm; (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1- methylethyOpiperaz e; NMR (DMSO-d 6 ) 7.6 (m, 2), 7.3 (m, 4), 6.9 (d, 2), 5.0-4.2 (m, 6), 3.5-3.1 (m, 4), 2.2 (m, 1 ), 1.2 (d, 3), 0.9 (d, 6) ppm; (2S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyOcarbonyl-2-(2-methylpropyl)pιperazιne, (2R,3R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,3-dιmethyipιperazιne, hydrochloride salt; NMR (DMSO-d 6 ) 7.8 (m, 2), 7.3 (m, 4), 6.9 (d, 2), 5.1-3.6 ( , 6), 3.2 (m, 4), 1.5-1.2 (m, 6) ppm; (3S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-butylpιperazιne; (3S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(1-methylpropyl)pιperazιne, (3R)-4-(4-fluorobenzyl)-1 -((4-chlorophenoxy)methyl)carbonyl-3-(2-methylpropyl)pιperazιne, (3R)-4-(4-fluorobenzyl)-1-((4-chloropheπoxy)methyl)carbonyl-3-butylpιperazιne, (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(benzyloxy)methyl- piperazme; NMR (CDCI 3 ) 7.3 (m, 8), 6.8 (m„ 5), 4.5 (m, 6), 3.6 (m, 5), 3.0 (m, 1 ), 2.7 (dd, 1 ), 2.3 (d, 1 ), 1.2 (d, 3) ppm; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxyethyl)pιperazιne dihydrochloπde salt; (2R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methylpιperazιne hydrochloride salt, (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-((4-acetylpιperazιn- 1-yl)methyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-((tπfluoroacetylamιno)- methyOpiperazine, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(ethoxycarbonyl)methylpιperazιne, hydrochloride salt; (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,5-dιmethylpιperazιne, hydrochloride salt; ('frans)-4-(4-fluorobenzy0-1-((2-acetyiamιno-4-chlorophenoxy)methyl)carbonyl- 2,5-dιmethylpιperazιne; NMR (DMSO-d 6 ) 9.5 (br s, 1 ), 8.1 (br s, 1 ), 7 7 (m, 2), 7.3 (m, 2), 7.0 (m, 2), 5.0 (m, 2), 4.3 (m, 3), 3.8-2.9 (m, 5), 2.1 (s,3), 1.2 (m, 6) ppm; 4-(4-fluorobenzyl)-1-((2-((acetylamιno)methyl)-4-chlorophenoxy)methyl)carbonyl- 2,5-methylpιperazιne; NMR (CDCI 3 ) 7.3 (m, 3), 7.1 (dd, 1 ), 7.0 (t, 2), 6.7 (d, 1 ), 4.7 (m, 2), 4.2-3.4 (m, 10), 3.0 (br s, 1 ), 2.7 (dd, 1 ), 2.5 (q, 4), 2.2 (d, 1 ), 2.0 (m, 4), 1.3 (m, 3), 0.9 (m, 3) ppm; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(((f-butoxycarbonyl)amιno)methyl- piperazine; 1-((4-chloro-2-(acetylamιno)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 10.9 (d, 1 ), 9.5 (s, 1 ), 8.1 (s, 1 ), 7.6 (d, 2), 7.3 (t, 2), 7.0 (m, 2), 5.0 (q, 2), 4.7 (m, 1 ), 4.3 (m, 2), 3.9-2.8 (m, 6), 2.1 (s, 3), 1.4 (d, 1.5), 1.3 (d, 1.5) ppm; (frans)-1-((4-chloro-2-(propylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (DMSO-d 6 ) 9.5 (d, 1 ), 8.2 (s, 1 ), 7.8 (t, 2), 7.3 (t, 2), 7.0 (dt, 2), 6.8 (dq, 1 ), 6.4 (d, 1 ), 5.2-4.3 (m, 5), 3.9-2.8 (m, 5), 1.8 (d, 3), 1.3 (m, 6) ppm, (frans)-1-((4-chloro-2-(/ ' so-propylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (DMSO-d 6 ) 9.5 (d, 1 ), 8.2 (s, 1 ), 7.8 (t, 2), 7.3 (t, 2), 7.0 (m, 2), 5.2-4.3 (m, 5), 3.9-2.7 (m, 6), 1.4-1.1 (m, 12) ppm; (frans)-1-((4-chloro-2-(methoxymethylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)piperazιne; NMR (DMSO-d 6 ) 9.3 (s, 1 ), 8.2 (s, 1 ), 7.8 (t, 2), 7.3 (t, 2), 7 1 (m, 2), 5.3-4.2 (m, 5), 4.0 (s, 2), 3.9-2.8 (m, 8), 1 4-1.2 (m, 6) ppm; (frans)-1 -((4-chloro-2-(2-(methoxycarbonyl)ethylcarbonylamιno)phenoxy)-methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 9.5 (s. 1 ), 8.1 (s, 1 ), 7.8 (t, 2), 7.3 (t, 2), 7.0 (m, 2), 5.2-4.2 (m, 5), 3.8 (q, 1 ), 3 7-3.2 (m, 5), 2.9-2.6 (m, 6), 1 4-1.2 (m, 6) ppm; (frans)-1-((4-chloro-2-(2-(ethoxycarbonyl)ethylcarbonylamιno)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fiuorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 9.6 (s. 1 ), 8.1 (s, 1 ), 7.8 (t, 2), 7.3 (t, 2), 7.0 (m, 2), 5.2-4.2 (m, 5), 4.0 (q, 2), 3.8 (q, 1 ), 3.6-3.2 (m, 3), 2.8-2.6 (m, 5), 1.4-1.2 (m, 9) ppm; (frans)-1-((4-chloro-2-(methylsulfonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (DMSO-d 6 ) 10.9 (d, 1 ), 9.3 (s. 1 ), 7.7 (d, 2), 7.3-7.2 ( , 4), 7.0 (d, 1 ), 5.0 (m, 2), 4.7 (m, 1 ), 4.4 (m, 3), 3.9 (m, 1 ), 3.6 (m, 1 ), 3.4-2.8 (m, 6), 1 4 (d, 1.5), 1.2 (d, 1.5) ppm; (frans)-1-((4-chloro-2-(bromomethylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 10.0 (s. 1 ), 8.4 (s, 1 ), 7.3 (m, 2), 7.0 (m, 3), 6.9 (m, 1), 4.7 (m, 3), 4.0 (s, 2), 3.8-3.1 (m, 5), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (brd, 3), 1.0 (brs, 3) ppm; (frans)-1-((4-chloro-2-(ethylcarbonylamino)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperaz e; NMR (CDCI 3 ) 9.4 (s, 1), 8.5 (s, 1), 7.3 (m, 2), 7.0 (m, 3), 6.8 (d, 1), 4.7 (m, 3), 3.5 (m, 3), 3.1 (m, 2), 2.7 (dd, 1), 2.5 (q, 1), 2.2 (d, 1), 1.3 (m, 6), 1.0 (m, 3) ppm; (frans)-1-((4-chloro-2-(acetylamιπomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 8.0 (br s, 1), 7.3 (m, 3), 7.1 (dd, 1), 7.0 (m, 2), 6.8 (brd, 1), 4.7 (m, 3), 4.4 (d, 1), 3.8-3.0 (m, 6), 2.7 (m, 1), 2.2 (m, 1), 2.0 (s, 3), 1.3 (m, 3), 0.9 (m, 3) ppm; (frat7S)-1-((4-chloro-2-(1-(methylsulfonyl)(methyl)amιnoethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.8 (m, 1), 5.6 (q, 1), 4.7 (m, 3), 4.2 (m, 1), 3.7 (m, 1), 3.5 (q, 2), 3.2 (m, 1), 3.1 (m, 1), 2.8 (d, 3), 2.7 (d, 3), 2.3 (brd, 1), 1.6 (d, 3), 1.3 (m, 3), 0.9 (m, 3) ppm; (fraπs)-1 -((4-chloro-2-(1 -(phenylsulfonyl)(methyi)amιnoethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιρerazιne; NMR (CDCI 3 ) 7.6 (d, 2), 7.3 (m, 6), 6.9 (t, 2), 6.8 (t, 1), 5.6 (q, 1), 4.6 (m, 3), 4.2 (m, 1), 3.6 (m, 2), 34 (d, 1), 3.0 (m, 1), 2.6 (m, 4), 2.4 (s, 3), 2.3 (m, 1), 1.3 (m, 6), 0.9 (m, 3) ppm; (fra/7s)-1-((4-chloro-2-(1-(acefyl)(methyl)aminoethyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.2 (m, 4), 7.0 (t, 2), 6.8 (m, 1), 6.0 (m, 1), 5.4 (q, 1), 4.6 (m, 3), 4.2 (m, 1), 3.5 (q, 2), 3.2 (m, 1), 3.0 (m, 1), 2.6 (m, 4), 2.2 (m, 3), 13 (m, 6), 0.9 (m, 3) ppm; (frans)-1-(2-(4-chlorophenyl)-3-(methylsulfonylamιno)propyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; NMR (CDCI 3 ) 7.3 (t, 4), 7.2 (br d, 2), 7.0 (t, 2), 5.0 (br s, 1), 4.6 (brs, 1), 4.0 (m, 1), 3.4 (m, 5), 3.0 (m, 2), 2.8 (s, 3), 2.6 (m, 2), 2.2 (brd, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (frat7s)-1-(2-(4-chlorophenyl)-3-(acetylamιno)propyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 4), 7.2 (brd, 2), 7.0 (t, 2), 5.2 (m, 1), 4.6 (brs, 1), 4.2 (m, 1), 3.8 (m, 1), 3.4 (m, 5), 3.0 (m, 1), 2.8 (s, 3), 2.6 (m, 2), 2.2 (m, 1), 1.2 (m, 3), 0.9 (m, 3) ppm; (fraπs)-1-(2-(4-chlorophenyl)-2-(methylsulfonyiamιno)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, NMR (CDCI 3 ) 7.3 (m, 5), 7.0 (t, 2), 6.6 (m, 1 ), 4.9 (q, 1 ), 4 6 (m, 0.5), 4.2 (br d, 0.5), 3.8 (m, 1 ), 3.5 (m, 1 ), 3.4 (m, 1 ), 3.0 (m, 2), 2.7 (m, 6), 2.2 (m, 1 ), 1.2 (m, 3), 0.8 (m, 3) ppm; (frat7s)-1-(2-(4-chlorophenyl)-2-(acetylamιno)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, NMR (CDCI 3 ) 7.8 (m, 1 ), 7.3 (m, 5), 7.0 (t, 2), 5.3 (m, 1 ), 4.6 (m, 0.5), 4.1 (t, 0.5), 3.5 (m, 1), 3 4 (m, 1 ), 3.0 (m, 3), 2.6 (m, 2), 2.2 (m, 1 ), 2 0 (m, 4), 1.2 (m, 3), 0.8 (m, 3) ppm; (frans)-1 -((4-chloro-2-((4-(2,5-dι(trιfluoromethyl)phenyicarbonyl)pιperazιn-1- yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 11.0 (m, 1 ), 8.1 (m, 2), 7.9 (t, 1 ), 7.7 (m, 1 ), 7 4 (d, 1 ), 7 3 (m, 2), 7 2 (m, 1 ), 5 4 (m, 1 ), 5.0 (m, 2), 4 4 (m, 6), 3 4 (m, 9), 3 0 (m, 1 ), 2.8 (m, 1 ), 1 4 (m, 3), 1 2 (m, 3) ppm, (frans)-1 -((4-chloro-2-((4-(benzylcarbony0pιperazιn-1-yl)methyl)phenoxy)methyl)-carbonyl-2,5- dιmethyl-4-(4-fluorobeπzyl)pιperazιne; NMR (DMSO-d 6 ) 1 1.0 (m, 1 ), 7 9 (t, 2), 7 7 (t, 1 ), 7.6, (s, 1 ), 7.5 (d, 1 ), 7.3 (m, 4), 7.2 (m, 3), 5 4 (m, 1 ), 5.0 (m, 2), 4 4 (m, 6), 3 7 (m, 2), 3 4 (m, 6), 3.0 (m, 2), 2.8 (m, 1 ), 1 4 (dd, 3), 1 2 (dd, 3) ppm, (frans)-1-((4-chloro-2-((4-((2,3,4-tπfluorophenyl)amιnocarbonyl)pιperazιn-1- yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 11.0 (m, 1 ), 9.0 (s, 1 ), 7.9 (t, 2), 7 7 (m, 1 ), 7 6 (s, 1 ), 7 5 (m, 1 ), 7 2 (m, 4) 5 4 (m, 1 ), 5.0 (m, 2), 4 4 (m, 6), 3.4 (m, 8), 3 1 (m, 2), 2.8 (m, 1 ), 1 4 (m, 3), 1 2 (m, 3) ppm, (frans)-1-((4-chloro-2-((4-((2-fluorophenyl)amιnocarbonyl)pιperazιn-1- yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 1 1.0 (m, 1 ), 8.6 (s, 1 ), 7.9 (t, 2), 7.7. (m, 1 ), 7.6 (s, 1 ), 7 4 (d, 1 ), 7 3 (m, 1 ), 7.3 (t, 2), 7.2 (m, 3), 5.4 (m, 1 ), 5.0 (m, 2), 4.3 (m, 6), 3.4 (m, 9), 3.1 (m, 2), 2.8 (m, 1 ), 1.4 (dd, 3), 1.2 (dd, 3) ppm; (frans)-1-((4-chloro-2-((Λ/-(2,6-difluorophenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobeπzyl)pιperazιne, NMR (CDCI 3 ) 9.6 (br s, 1 ), 8.6 (s, 1 ), 7 4 (qum, 1 ), 7.3 (t, 2), 7.0 (m, 5), 6.9 (d, 1 ), 4.7 (m, 3), 4.1 (br s, 0.5), 3.8 (br s, 0.5), 3 5 (q, 2), 3.2 (m, 1 ), 3 0 (m, 1 ), 2.6 (dd, 1 ), 2.2 (d, 1), 1.2 (m, 3), 0.9 (m, 3) ppm; (frat?s)-1-((4-chloro-2-(ethenylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 9.8 (d, 1 ), 8.6 (s, 1 ), 7.3 (m, 3), 7.0 (t, 3), 6.9 (d, 1), 6.4 (dd, 2), 5.8 (dd, 1), 4.7 (m, 3), 3.6 (m, 1 ), 3.5 (q, 2), 3.2 (m, 1), 3.0 (m, 1), 2.7 (dd, 1 ), 2.2 (dd, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-(cyclopropylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 9.7 (br s, 1 ), 8.4 (s, 1 ), 7.3 (m, 2), 7.0 (m, 3), 6.8 (d, 1 ), 4.7 (m, 3), 3.7 (m, 1 ), 3.5 (q, 2), 3.1 (m, 2), 2.7 (dd, 1 ), 2.2 (dd, 1 ), 1.7 (m, 1 ), 1.3 (m, 3), 1.0 (m, 5), 0.8 (m, 2) ppm; (frans)-1-((4-chloro-2-(cyclopentylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 9.3 (br s, 1 ), 8.5 (s, 1 ), 7.3 (t, 2), 7 0 (m, 3), 6.8 (d, 1 ), 4.7 (m, 3), 3.7 (m, 1 ), 3.5 (q, 2), 3.1 (m, 2), 2.8 (qum, 1 ), 2.7 (dd, 1 ), 2.2 (dd, 1 ), 1.9 (m, 3), 1.8 (m, 1 ), 1.6 (m, 3), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-((furan-2-yl)carbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (DMSO-d 6 ) 10.4 (br s, 1), 9.7 (br d, 1), 8.2 (br s, 1 ), 7.9 (s, 1 ), 7.7 (m, 2), 7.3 (m, 3), 7.2 (s, 2), 6.7 (d, 1 ), 5.3 (br d, 1 ), 5.0 (m, 2), 4.7 (m, 0.5), 4.5 (m, 0.5), 4.2 (m, 3), 3.6 (m, 1 ), 3.4 (m, 1 ), 2.8 (m, 1 ), 1.3 (m, 3), 1.2 (m, 3) ppm; (frans)-1-((4-chloro-2-(phenylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 10.0 (s, 1 ), 8.6 (s, 1 ), 8.1 (d, 2), 7 5 (m, 3), 7.3 (t, 2), 7.0 (t, 3), 6.8 (d, 1 ), 4.7 (m, 3), 3.7 (m, 1 ), 3 5 (q, 2), 3 1 (m, 2), 2.7 (dd, 1 ), 2.2 (dd, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-(2-(4-chlorophenyl)-2-((ethoxycarbonylmethylcarbonylamino)ethyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 8.6 (m, 1 ), 7.2 (s, 6), 7.0 (t, 2), 5 4 ( , 1 ), 4.2 (q, 2), 3.8 (m, 1 ), 3.5 (m, 1 ), 3.4 (m, 3), 3.0 (m, 3), 2.6 (m, 2), 2.2 (m, 2), 1.3 (m, 4.5), 1.1. (m, 1.5 ), 0.9 (dd, 1.5), 0.7 (dd, 1.5) ppm; (frans)-1-(2-(4-chlorophenyl)-2-(A/-/ ' so-propylureιdo)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 6), 7.0 (t, 2), 5.2 (t, 1), 4.6 (m, 0.5), 4.4 (m, 1 ), 4.2 (t, 0.5), 3.8 (m, 1 ), 3.5 (m, 1 ), 3.4 (m, 1 ), 3.0 (m, 3), 2.6 (m, 1 ), 2.2 (m,1 ), 1 1 (m, 9), 0.9 (dd, 1.5), 0.8 (dd, 1.5) ppm; (frans)-1-(2-(4-chlorophenyl)-2-(A/-(2-chloroethyl)ureido)ethyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 6), 7.0 (t, 2), 5.2 (t, 2), 4.6 (m, 0.5), 4.2 (t, 0.5), 3.5 (m, 6), 3.0 (m, 4), 2.6 (m, 1 ), 2.2 (m,1 ), 1.1 (m, 3), 0.9 (dd, 1.5), 0.8 (dd, 1 5) ppm; (frans)-1-(2-(4-chiorophenyl)-2-((2-nιtrophenyl)carbonylamιno)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 8.1 (d, 1), 7.7 (q, 1), 7.6 (t, 2), 7.3 (m, 6), 7.0 (t, 2), 5.6 (m, 1 ), 4.6 (m, 0.5), 4.1 (t, 0.5), 3.7-3.2 (m, 3), 3.0 (m, 4), 2.6 (m, 1 ), 2.2 (m, 1 ), 1.2 (m, 3), 0.9 (m, 3) ppm; (frans)-1-(2-(4-chlorophenyl)-2-((4-methoxyphenylmethyl)carbonylamιno)ethyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 8), 7.0 (t, 2), 6.9 (d, 2), 5.3 (m, 1 ), 4.6 (m, 0.5), 4.1 (t, 0.5), 3.8 (s, 3), 3.5 (m, 3), 3.4-2.8 (m, 6), 2.6 (m, 1 ), 2.2 (m, 1 ), 1.2 (m, 3), 0.8 (m, 3) ppm; (frans)-1-(2-(4-chlorophenyl)-2-((2,4-dιnιtrophenyl)sulfonylamιno)ethyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 8.6 (s, 1 ), 8.2 (d, 1 ), 7.8 (m, 1 ), 7 3 (m, 4), 7 0 (t, 2), 6.9 (t, 2), 5.0 (m, 1 ), 4.6 (m, 0.5), 4.1 (m, 0.5), 3.5 (m, 1 ), 3.4 (m, 1 ), 3.0 (m, 5), 2.6 (m, 1 ), 2.2 (m, 1 ), 1.1 (m, 3), 0.8 (m, 3) ppm; (fraπs)-1-(2-(4-chlorophenyl)-2-(cyclopropylcarbonylamιno)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 6), 7.0 (t, 2), 5.2 (m, 1 ), 4.6 (m, 0.5), 4.2 (m, 0.5), 3.5 (m, 2), 3.4 (m, 1 ), 3.0 (m, 3), 2 6 (m, 2), 2.2 (m, 1 ), 1.5 (m, 1 ), 1.2 (m, 3), 0.9 (m, 3.5), 0.7 (m, 3.5) ppm; (frans)-1-(2-(4-chlorophenyl)-2-((2-cyclopropylethyl)carbonylamιno)ethyl)carbonyl-2,5-dιmethyl- 4-(4-fluorobenzyl)pιperazιπe; NMR (CDCI 3 ) 7.3 (m, 6), 7.0 (t, 2), 5 4 (m, 1 ), 4.6 (m 0 5), 4.2 (m, 0.5), 3.6 (m, 2), 3.4 (m, 1 ), 3.0 (m, 4), 2.6 (m, 1 ), 2.2 (m, 2), 1.6 (m, 10), 1.2 (m, 3), 1.1 (m, 2), 0.8 (m, 3) ppm; (fraπs)-1-(2-(4-chlorophenyl)-3-((2-methylpropyl)carbonylamιno)propyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)piperazιne;; NMR (CDCI 3 ) 7.3 (d, 4), 7.2 (d, 2), 7.0 (t, 2), 6.0 (br s, 1 ), 4.6 (m, 0.5), 4.2 (m, 0.5), 3.6 (m, 2), 3.4 (m, 3), 3.0 (m, 2), 2.6 (m, 3), 2.2 (d, 1 ), 2.0 (m, 4), 1.2 (m, 3), 0.9 (m, 9) ppm; (frans)-1-(2-(4-chlorophenyl)-3-(cycloppentylcarbonylamιno)propyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (d, 4), 7.2 (d, 2), 7.0 (t, 2), 6.0 (br s, 1 ), 4.6 (m, 0.5), 4.2 (m, 0.5), 3.6 (m, 2), 3.4 (m, 3), 3.0 (m, 2), 2.6 (m, 3), 2.4 (m, 1 ), 2.2 (d, 1 ), 1.6 (m, 8), 1.1. (m, 4), 0.9 (m, 4) ppm; (fraπs)-1-(2-(4-chlorophenyO-3-(/V-(f-butyl)ureido)propyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (d, 4), 7.2 (d, 2), 7.0 (t, 2), 4.6 (m, 1.5), 4.2 (m, 0.5), 3.6 (m, 2), 3.4 (m, 4), 3.2 (m, 1 ), 3.0 (m, 1 ), 2.6 (m, 2), 2.2 (d, 1 ), 1.3 (s, 9), 1.2 (m, 3), 0.9 (m, 3) ppm; (fraπs)-1-(2-(4-chlorophenyO-3-(/V'-(ethyl)ureido)propyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (d, 4), 7.2 (d, 2), 7.0 (t, 2), 5.1 (m, 1 ), 4.9 (m, 1), 4.6 (m, 0.5), 4.2 (m, 0.5), 3.6 (m, 2), 3.4 (m, 4), 3.2 (m, 3), 3.0 (m, 1 ), 2.6 (m, 3), 2.2 (m, 1 ), 1.1 (m, 6), 0.9 (m, 3) ppm; (frans)-1-(2-(4-chlorophenyO-3-(/V'-(3-choropropyl)ureido)propyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (d, 4), 7.2 (d, 2), 7.0 (t, 2), 5.6 (br s, 1 ), 5.9 (s, 1 ), 4.6 (m, 0.5), 4.2 (m, 0.5), 3.6 (m, 5), 3.4 (m, 5), 3.2 (m, 1 ), 3.0 (m, 1 ), 2.6 ( , 3), 2.2 (d, 1 ), 2.0 (t, 2), 1.2 (m, 3), 0.9 (m, 3) ppm; (frans)-1-(2-(4-chlorophenyl)-3-((morphoiin-4-yl)carboπylamino)propyl)carbonyl-2,5-dimethyl-4- (4-fluorobenzyl)piperazine; NMR (CDCI 3 ) 7.3 (d, 4), 7.2 (d, 2), 7.0. (t, 2), 5.8 (br d, 1 ), 4.6 (m, 0.5), 4.2 (m, 0.5), 3.6 (m, 6), 3.4 (m, 4), 3.3 (t, 4), 3.0 (m, 2), 2.6 (m, 3), 2.2 (m, 1 ), 1.2 (m, 3), 0.9 (m, 3) ppm; (fraπs)-1-((4-chloro-2-((Λ/'-(methoxycarbonylmethylcarbonyl)-Λ/'- (methyl)glycinamido)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)piperazine; NMR (CDCI 3 ) 9.6 (br s, 1 ), 8.4 (d, 1 ), 7.3 (dd, 2), 7.0 (t, 3), 6.8 (d, 1 ), 4.7 (m, 3), 4.3 (s, 2), 3.8 (s, 3), 3.6 (m, 4), 3.5 (m, 2), 3.1 (m, 4), 2.7 (dd, 1 ). 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-((/V'-(2-methoxycarbonylethyl)carbonyl-/V- (methyl)glycinamido)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)piperazine; NMR (CDCI 3 ) 9.6 (br s, 1 ), 8.4 (d, 1 ), 7.3 (dd, 2), 7.0 (t, 3), 6.8 (d, 1 ), 4.7 (m, 3), 4.3 (s, 3), 3.8 (s, 3), 3.6 (q, 2), 3.2 (s, 3), 3.1 (s, 2), 2.7 (m, 5), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-((W-(3-methylbenzyl)aminocarbonyl-Λ/'- (methyl)glycinamido)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 9.6 (br s, 1 ), 8.4 (d, 1 ), 7.3 (dd, 2), 7.2 (t, 1 ), 7.0 (m, 6), 6.8 (d, 1 ), 5.4 (t, 1 ), 4.6 (m, 3), 4.4 (d, 2), 4.3 (s, 2), 3.8 (m, 1 ), 3.5 (q, 2), 3.1 (m, 5), 2.6 (m, 1 ), 2.3 (s, 3), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-((A/-(3-tπfluoromethyl-4-fluorophenyl)carbonyl-Λ/- (methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, NMR (CDCI 3 ) 9 8 (br s, 1 ), 8 4 (d, 1 ), 8 1 (br s, 1 ), 7 6 (m, 2), 7 3 (dd, 2), 7 0 (m, 4), 6 8 (d, 1 ), 4 7 (m, 3), 4 3 (t, 2), 3 7 (m, 1 ), 3 6 (q, 2), 3 2 (s, 3), 3 1 (m, 2), 2 7 (m, 1 ), 2.2 (d, 1 ), 1 3 (m, 3), 0 9 (m, 3) ppm, (frans)-1-((4-chloro-2-((Λ/'-(4-methylbenzyl)amιnocarbonyl-Λ/- (methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, NMR (CDCI 3 ) 9 6 (br s, 1 ), 8 4 (d, 1 ), 7 3 (m, 2), 7 2 (d, 2), 7 1 (d, 2), 7 0 (m, 3), 6 8 (d, 1 ), 5 4 (t, 1 ), 4 7 (m, 3),4 4 (d, 2), 4 2 (d, 2), 3 8 (m, 1 ), 3 6 (q, 2), 3 1 ( , 5), 2 7 (m, 1 ), 2 3 (s, 3), 2 2 (d, 1 ), 1 3 (m, 3), 0 9 (m, 3) ppm, (frans)-1-((4-chloro-2-((Λ -(3-chlorophenyl)carbonyl-Λ/- (methyl)glycιnamιdo)phenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, NMR (CDCI 3 ) 9 9 (br s, 1 ), 8 4 (d, 1 ), 7 5 (s, 1 ), 7 3 (m, 5), 7 0 (t, 3), 6 8 (d, 1 ), 4 7 (m, 3), 4 4 (br s, 2), 4 1 (m, 1 ), 3 6 (m, 1 ), 3 5 (q, 2), 3 2 (m, 3), 3 0 (m, 1 ), 2 7 (dd, 1 ), 2.2 (d, 1 ), 1 3 (m, 3), 0 9 (m, 3) ppm, (fraπs)-1-((4-chloro-2-((Λ/-(4-fluorobenzyl)amιnocarbonyl-/V- (methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, NMR (CDCI 3 ) 9 7 (br s, 1 ), 8 4 (s, 1 ), 7 3 (m, 4), 7 0 (m, 5) 6 8 (d, 1 ), 5 5 (t, 1 ), 4 7 (m, 2), 4 4 (d, 2), 4 2 (m, 2), 3 6 (m, 1 ), 3 5 (q, 2), 3 1 (m 5) 2 7 (m 1 ), 2 2 (d, 1 ), 1 3 (m, 3), 0 9 (m, 3) ppm, (frar7s)-1-((4-chloro-2-(Λ '-(methoxymethylcarbonyl)glycιnamιdo)phenoxy)methyl)-carbonyl-2 5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 10 1 (br s, 1 ), 8 4 (d, 1 ), 7 3 (t, 3), 7 0 (t, 3), 6 8 (d, 1 ), 4 7 (m, 3), 4 2 (d, 2), 4 0 (s, 2), 3 6 (m, 1 ), 3 5 (q, 2), 3 4 (s, 3), 3 1 (m, 2), 2 7 (dd, 1), 2 2 (d, 1 ), 1 3 (m, 3), 0 9 (m, 3) ppm, (frans)-1 -((4-chloro-2-(Λ/'-(ethoxycarbonylamιnocarbonyl)- glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 9 9 (br s, 1 ), 8 4 (m, 2), 7.3 (m, 3), 7 0 (m, 3), 6.8 (d, 1 ), 4 7 (m, 3), 4 4 (m, 6), 3 6 (m, 1 ), 3.5 (q, 2), 3 1 (m, 2), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 6), 0 9 (m, 3) ppm, (frans)-1-((4-chloro-2-(Λ/-(2-ιodophenylcarbonyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 10 4 (br s, 1 ), 8 4 (d, 1 ), 7 9 (d 1 ), 7.5 (d, 1 ), 7.4 (t, 1 ), 7.3 (m, 2), 7.1 (t, 1 ), 7.0 (t, 3), 6.8 (m, 2), 4.7 (m, 3), 4 4 (d, 2), 3.6 (m, 1 ), 3.5 (q, 2), 3.1 (m, 2), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (fΛans)-1-((4-chloro-2-(Λ/'-(2,3-difluorophenyicarbonyl)glycιnamιdo)phenoxy)-methyl)carboπyl- 2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 10.3 (br s, 1 ), 8.4 (d, 1 ), 7.8 (t, 1 ), 7.5 (qum, 1 ), 7.3 (m, 3), 7.2 (m, 1 ), 7.0 (t, 3), 6.8 (d, 1 ), 4.7 (m, 3), 4.4 (d, 2), 3.6 (m, 1 ), 3.5 (q, 2), 3.1 (m, 2), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-(Λ/'-((4-phenoxyphenyi)amιnocarbonyl)glycιnamido)phenoxy)- methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)piperazιne; NMR (CDCI 3 ) 9.9 (br s, 1 ), 8.3 (br s, 1 ), 7.3 (m, 6), 7.0 (t, 6), 6.8 (m, 3), 6.5 (m, 1 ), 4.7 (m, 3), 4.4 (m, 2), 3.6 (m, 1 ), 3 5 (q, 2), 3 1 (m, 2), 2 7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (fΛans)-1-((4-chloro-2-(Λ/'-(2,4-dιflurophenylcarbonyl)glycιnamιdo)phenoxy)methyl)-carbonyl-2.5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 10.3 (br s, 1 ), 8 4 (d, 1 ), 8.1 (q, 1 ), 7.5 (m, 1 ), 7.3 (m, 2), 7.0 (t, 3), 6.8 (m, 3), 4.7 (m, 3), 4.4 (d, 2), 3.6 (m, 1 ), 3.5 (q, 2), 3.1 (m, 2), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-((2-iodophenylcarbonyi)amιnomethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 8.0 (m, 1 ), 7.8 (d, 1 ), 7.3 (m, 5), 7.2 (dd, 1 ), 7.0 (m, 3), 6.8 (d, 1 ), 4.8 (m, 3), 4 6 (d, 2), 4 4 (m, 0.5), 3.9 (m, 0.5), 3.5 (q, 2), 3.1 (m, 2), 2.6 (m, 1 ), 2.2 (m, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-((ethoxycarbonylmethylcarbonyl)amιnomethyl)phenoxy)-methyl)carbonyl- 2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 8.4 (br s, 1 ), 7.3 (m, 3), 7 2 (dd, 1 ), 7.0 (m, 2), 6.8 (d, 1 ), 4.8 (m, 3), 4.5 (d, 2), 4.2 (m, 3), 3.6 (m, 1 ), 3.5 (q, 2), 3.3 (s, 2), 3.1 (m, 1 ), 2.6 (m, 1 ), 2.2 (d, 1 ), 1.3 (m, 6), 0.9 (m, 3) ppm; (frans)-1 -((4-chloro-2-(A/-(3-chloropropyl)ureidomethyl)phenoxy)methyl)carbonyl-2,5-dimethyl- 4-(4-fluorobenzyl)piperazιne; NMR (CDCI 3 ) 7.3 (m, 3), 7.2 (dd, 1 ), 7.0 (m, 2), 6.8 (d, 1 ), 4.8 (m, 4), 4.4 (d, 2), 4.2 (m, 1 ), 3.6 (m, 5), 3.3 (m, 3), 3.1 (m, 1 ), 2.6 (m, 1 ), 2.2 (d, 1 ), 1.9 (qu , 2), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-(Λ/-(2-fluoro-6-trifluoromethylphenyl)ureιdomethyl)phenoxy)- methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 8.2 (m, 1 ), 7.3 (m, 6), 7.2 (dd, 1), 7.0 (t, 2), 6.8 (d, 1), 4.8 (m, 3), 4.4 (d, 2), 3.8 (m, 1), 3.5 (q, 2), 3.2 (m, 1 ), 3.1 (m, 1 ), 2.6 (m, 1 ), 2.2 (m, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-((3-fluorophenyl)carbonyiamιnomethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fiuorobenzyl)piperazιne; NMR (CDCI 3 ) 8.6 (m, 1 ), 7.8 (t, 2), 7.3 (m, 4), 7.2 (dd, 1 ), 7.1 (dt, 1 ), 7.0 (t, 2), 6.8 (d, 1 ), 4.8 (m, 3), 4.6 (d, 2), 3.8 (m, 1 ), 3.5 (q, 2), 3.1 (m, 2), 2.6 (m, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-(/V-(2-(ethoxycarbonyl)ethyl)ureιdomethyl)phenoxy)-methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)piperazιne; NMR (CDCI 3 ) 7.3 (m, 3), 7.2 (dd, 1 ), 7.0 (t, 2), 6.9 (m, 1), 6.8 (d, 1), 5.1 (m, 1), 4.8 (m, 3), 4.4 (d, 2), 4.1 (q, 2), 3.6 (m, 2), 3.4 (m, 3), 3.2 (m, 1 ), 3.1 (m, 2), 2.7 (m, 1 ), 2.5 (t, 2), 2.2 (d, 1 ), 1.3 (m, 6), 0.9 (m, 3) ppm; (ftans)-1-((4-chloro-2-((2,5-di(tπfluoromethyl)phenyl)carbonylamιnomethyl)- phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 8 9 (m, 1 ), 7.8 (m, 2), 7.2 (s, 1 ), 7.3 (m, 3), 7.2 (dd, 1 ), 7.0 (t, 2), 6.8 (d, 1 ), 4.8 (m, 3), 4 6 (d, 2), 4.4 (m, 0.5), 3.9 (m, 0.5), 3.5 (q, 2), 3.1 (m, 2), 2.6 (m, 1 ), 2.2 (m, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; and (frans)-1 -((4-chloro-2-(/V'-(2-(phenyl)cyclopropyl)ureidomethyl)phenoxy)methyl)carbonyl-2, 5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 8), 7.0 (m, 3), 6.8 (d, 1 ), 4.9 (s, 1 ), 4.6 (d, 2), 4.4 (m, 2), 3.8 (m, 1 ), 3.5 (q, 2), 3.2 (m, 1 ), 3.0 (m, 1 ), 2.7 ( , 2), 2.2 (m, 1 ), 2.0 (m, 1 ), 1.3 (m, 5), 0.9 (m, 3) ppm C. In a similar manner, the following compounds of formula (lb) were made. 1-(2-(4-chlorophenyl)ethenyi)carbonyl-4-(4-fluorobenzyl)pιperazιne; 1-(2-(4-chlorophenyl)ethyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; 1-(1-(f-butoxycarbonyl)amιno-2-(4-chlorophenyl)ethyl)carbonyl-4-(benzyl)pιperazιne, 1-(3-(f-butoxycarbonyl)amιno-2-(4-chlorophenyl)propyl)carbonyl-4-(4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 7.2 (m, 8), 4.8 (m, 1 ), 3.6-3.3 (m, 8), 2.6 (m, 2), 2.3 (m, 3), 2.1 (m, 1 ), 1 4 (s, 9) ppm; 1-(2-(3,4,5-trimethoxyphenyl)ethenyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7 6 (d, 1 ), 7.3 (m, 4), 6.7 (m, 3), 3.9-3.6 (m, 13), 3.5 (s, 2), 2.5 (m, 4) ppm; 1-(1-(3,4-dιmethoxyphenyl)-2-(4-chlorophenyl)ethenyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-(2-(3,4,5-trimethoxyphenyl)ethyl)carbonyl-4-(4-chlorobenzyl)piperazine; 1-(((acetyl)amino)(4-chlorophenyl)methyl)carbonyl-4-(4-fluorobenzyl)piperazine, hydrochloride salt. D. in a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 2 Compounds of Formula (la) A. To a solution of (2R,5S)-1-(chloro)acetyl-4-(4-fluorobenzyl)-2,5-dιmethyl- piperazme (0.29 g, 1 mmol) in anhydrous DMF (5 mL) was added 4-hydroxy-3- rπethoxyphenylacetonitrile (0.20 g, 1.2 mmol) and potassium carbonate (0.28 g, 2 mmol, powdered). The resultant mixture was stirred at 50°C. After 15 hours analysis by analytical HPLC (HPLC on a C18 Vydac column with 20-70% acetonitnle in water gradient with 0.1 % tnfluoroacetic acid) showed complete consumption of starting material had occurred. The mixture was poured into water and extracted with three portions of ethyl acetate. The combined organic extracts were washed sequentially with 0.5 N aqueous KOH solution, water, then brine. It was then dried over MgS0 , filtered and concentrated in vacuo to afford a yellow oil This was dissolved in ethyl acetate and treated with a solution of HCI in anhydrous ether. Filtration of the resultant solid afforded 0.38 g (85% yield) of (2R,5S)-1-((4-(cyano)methyl-2- methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)-2,5-dιmethylpιperazιne, hydrochloric acid salt as a white solid: NMR (DMSO-d 6 ) 1 1.5 (br s, 1 ), 7.6 (m, 4), 6.9 (m, 3), 4.8 (br s, 2), 4 4 (br s. 3), 4.0 (m, 1 ), 3.9 (s, 2), 3.8 (s, 3), 3.6 (m, 1 ), 3.3 (m, 2), 3.2-2.9 (m, 3) ppm B. In a similar manner, other compounds of formula (la) were made. (fraπs)-1-((4-fluoro-3-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 10.4 (br d, 1 ), 7.7 (m, 2), 7.2 (m, 4), 6.9 (br s, 1 ), 5.0 (m, 1 ), 4 8 (m, 2), 4.3 (m, 3), 3.7 (m, 2), 3.3 (m, 2), 2.9 (m, 1 ), 1 4-1.2 (m, 6) ppm; 1-((2-acetylamιnophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 10 6 (br s, 1 ), 9.4 (s, 1 ), 8.0 (d, 1 ), 7.8 (br s, 2), 7.2 (t, 2), 6.9 (m, 3), 5.0 (m, 3), 4.3 (m, 3), 3.8 (q, 1 ), 3.6 (br s, 1 ), 3.4 (m, 1 ), 2.8 (m, 1 ), 2.1 (s, 3), 1.3 (dd, 3), 1.2 (d, 3) ppm, 1-((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-2-(methoxycarbonyl)methyl- 4-(4-fluorobenzyl)pιperazιne; 1 -((3,4,5-trimethoxyphenoxy)methyl)carbonyl-2-(ethoxycarbonyl)-4-(4-fluorobenzyl)piperazine; (c/s)-1-((3,4,5-trimethoxyphenoxy)methyl)carbonyl-2,6-dimethyl-4-(4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 7.3 (m, 2), 7.0 (t, 2), 6.2 (s, 2), 4.7-4.2 (m, 4), 3.8 (m, 9), 3.5 (s, 2), 2.6 (d, 2), 2.2 (dd, 2), 1.3 (m, 6) ppm; 1-((3,4,5-trimethoxyphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 2), 7.0 (t, 2), 6.2 (s, 2), 4.6 (s, 3), 4.4 (m, 1 ), 4.1 (m, 1 ), 3.8 (s, 6), 3.85 (s, 3), 3.5 (m. 2), 2.8 (d, 1 ), 2.6 (d, 1 ), 2.1 (m, 2), 1.3 (m, 3) ppm; 1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 4.4 (m, 1 ), 4.1 (m, 1 ), 3.7 (m, 1 ), 3.4 (m, 2), 2.8 (m, 1 ), 2.6 (d, 1 ), 2.0 (m, 2), 1.3 (m, 3) ppm; 1-((4-chlorophenoxy)methyl)carbonyl-3-methyl-4-(4-fluorobenzyl)piperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 4.0 (m, 2), 3.7 ( , 1 ), 3 4-2.9 (m, 3), 2.7 (m, 1 ), 2.5 (m, 1 ), 2.1 (m, 1 ), 1.1 (m, 3) ppm; (2S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; (2R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)piperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.6 (s, 2), 4.4 (m, 1 ), 4.1 (m, 1 ), 3.7 (m, 1 ), 3.4 (m, 2), 2.8 (m, 1 ), 2.6 (d, 1 ), 2.0 (m, 2), 1.3 (m, 3) ppm; 4-((4-chlorophenoxy)methyl)carbonyl-3-(((4-chlorophenyl)amino)carbonyl)methyl- 1 -(benzyl)piperazιn-2-one; 1 -((phenoxy)methyl)carbonyl-2-ethyl-4-(4-fluorobeπzyl)pιperazιne; 1-((4-chlorophenoxy)methyl)carbonyl-2-hydroxymethyl-4-(4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4 7-4.5 (m, 3), 4.2-3.3 (m, 5), 3.2-2 7 (m, 2), 2.3-2.0 (m, 4) ppm; 1-(1 -(4-chlorophenoxy)-1-methylethyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; (2S,5R)-1-((4-chloro-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 2), 7.0 (t, 2), 6.2 (s, 2), 4.6 (m, 34), 4.2 (m, 1 ), 3.8 (m, 6), 3.5 (m, 3), 3.0 (m, 1 ), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 4), 0.9 (m, 3) ppm; (2R,5S)-1-((4-chloro-3,5-dimethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 2), 7.0 (t, 2), 6.2 (s, 2), 4.6 (m, 3), 4.2 (m, 1), 3.8 (m, 6), 3.5 (m, 3), 3.0 (m, 1), 2.7 (dd, 1), 2.2 (d, 1), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-3,5-dimethoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 2), 7.0 (t, 2), 6.3 (s, 2), 4.7 (m, 2), 4.2 (m, 1), 3.8 (s, 6), 3.5 (m, 4), 3.0 (m, 1 ), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 ( , 3) ppm; (2S,5R)-1-((4-bromo-3,5-dimethoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, hydrochloride salt; NMR (DMSO-d 6 ) 10.7 (d, 1 ), 7.8 (m, 2), 7.3 (m, 2), 6.3 (s, 2), 4.9 (m, 2), 4.3 (m, 2), 4.0-2.8 (m, 12), 1.4-1.2 (m, 6) ppm; (2S,5R)-1-((4-nitro-3-formylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 10.4 (s, 1 ), 8.2 (d, 1 ), 7.3 (m, 4), 7.0 (t, 2), 4.8 (m, 3), 4.2-2.3 (m, 7), 1.3 (m 3), 1.0 (m, 3) ppm; (frans)-1-((4-chloro-2-(aminocarbonyl)pheπoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 9.2 (br s, 1 ), 8.2 (s, 1 ), 7.4 (m, 3), 7.0 (t, 2), 6.8 (d, 1 ), 5.9 (s, 1 ), 5.0-4.0 (m, 3), 3.8-3.0 ( , 5), 2.8 (d, 1 ), 2.3 (d, 1 ), 1.3 (m, 3), 1.0 (br s, 3) ppm; (2R,5S)-1-((4-chloro-2-(aminocarbonyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 9.2 (br s, 1 ), 8.2 (s, 1 ), 7.4 (m, 4), 7.0 (t, 2), 6.8 (d, 1 ), 5.8 (s, 1 ), 4.7 (m, 2), 3.7-3.1 (m, 5), 2.8 (d, 1 ), 2.3 (d, 1 ), 1.3 (d, 3), 1.0 (br s, 3) ppm; (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-((amino)carbonyloxy)methyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-3-nitrophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobeπzyOpiperazine, hydrochloride salt; NMR (DMS0-d 6 ) 1 1 (br d, 1 ), 7.9 (br s, 1 ), 7.6 (m, 2), 7.3 (m, 4), 5.2 (d, 1 ), 5.0 (m, 2), 4.3 (m, 4), 4.0 (m, 1 ), 3.6 (m, 2), 1.3 (m, 6) ppm; (frat7s)-1-((4-chloro-2-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, hydrochloride salt; NMR (DMSO-d 6 ) 10.9 (br d, 1 ), 7.9 (br s, 2), 7.6 (m, 1 ), 7.3 (m, 4), 5.0 (m, 2), 4.5 (s, 2), 4.3 (m, 2), 3.7-3.3 (m, 6), 1.3 (m, 6) ppm; (frans)-1-((4-chloro-2-aminophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, dihydrochloride salt; NMR (DMSO-d 6 ) 7.7 (br s, 3), 7.3 (m, 5), 5.2 (d, 1 ), 5.0 (m, 2), 4.7-4.2 (m, 4), 3.9-3.4 (m, 3), 1.3 (m, 6) ppm; (fraπs)-1-((2-(aminocarbonyl)p enoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 9.1 (br s, 1 ), 8.2 (d, 1 ), 7.4 (dd, 1 ), 7.3 (br s, 2), 7.1 (t, 1 ), 7.0 (m, 2), 6.9 (d, 1 ), 5.8 (br s, 1 ), 4.7 (m, 2), 4.2 (m, 1 ), 3.7-3.4 (m, 3), 3 0 (br s, 1 ), 2.7 (br s, 1 ), 2.3 (d, 1 ), 1.3 (m, 3), 1.0 (m, 3) ppm; (frat7s)-1-((4-chloro-2-amιno-5-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, dihydrochloride salt; NMR (CDCI 3 ) 10.9 (br d, 1 ), 7.8 (m, 2), 7.5 (dd, 1), 7.3 (m, 2), 6.8 (s, 1 ), 5.0 (m, 3), 4.3-3.2 (m, 7), 1.4-1.2 (m, 6) ppm; (frans)-1-((4-methyl-2-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, hydrochloride salt; NMR (DMSO-d 6 ) 10.9 (br d, 1 ), 10 4 (s, 1 ), 7.9 (s, 2), 7.5 (m, 2), 7.3 (m, 2), 7.0 (d, 1 ), 5.2 (m, 1 ), 5.0 (m, 2), 4.6 (m, 1 ), 4 3 (m, 3), 3 6 (m, 2), 2.8 (m, 1 ), 2.5 (s, 3), 1 4-1 1 (m, 6) ppm; (frans)-1-((4-chloro-2-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 10.9 (br d, 1 ), 10.4 (s, 1 ), 7.8 (s, 1 ), 7 5 (dd, 1 ), 7.3 (dd, 2), 7.0 (m, 3), 4.8 (m, 3), 4 1 (m, 1 ), 3.5 (m, 3), 3.0 (br s, 1 ), 2 7 (dd, 1 ), 2 5 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((2-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e hydrochloride salt, NMR (DMSO-d 6 ) 11.0 (d,1 ), 7 8 (t, 2), 7 3 (t, 2), 7.1 (m, 2), 6.8 (m, 2), 4.9-3.3 (m, 9), 2.8 (t, 1 ), 2.2 (s, 3), 1 4-1.1 (m, 6) ppm, (frans)-1-((2-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, hydrochloride salt, NMR (DMSO-d 6 ) 1 1.0 (d, 1 ), 7.8 (t, 2), 7 3 (m, 3), 7.1 (t, 1 ), 6.9 (m, 2), 5.0-3.2 (m, 1 1 ), 2.8 (t, 1 ), 1 4-1 1 (m, 6) ppm, (frans)-1-((3-chloro-5-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, hydrochloride salt, NMR (DMSO-d 6 ) 10 8 (d, 1 ), 7.8 (m, 2), 7.3 (t, 2), 6.6 (s, 2), 6.5 (br s, 1 ), 5.0-3.2 (m, 12), 2.8 (m, 1 ), 1 4-1.2 (m, 6) ppm, (frans)-1-((2-methoxy-5-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, hydrochloride salt; NMR (DMSO-d 6 ) 11.1 (d, 1 ), 7.9 (m, 2), 7 7 (br s, 1), 7.2 (m, 4), 5.2-3.3 (m, 12), 2.8 (t, 1 ), 1.4-1.2 (m, 6) ppm; 1-((phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 11 (br d, 1), 7.7 (m, 2), 7.3 (m, 4), 6.9 (m, 3), 4.9 (m, 3), 4.3 (m, 3), 4.0-2.8 (m, 5), 1.4 (d, 1.5), 1.2 (d, 1.5) ppm; (frat7s)-1-((4-chlorophenylamιno)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ).7.4 (dd, 2), 7.1 (m, 4), 6.6 (d, 2), 5.8 (t, 1 ), 4.5 (br s, 0.5), 4.0 (br , 1.5), 3.8 (br m, 1), 3.8-3.3 (m, 3), 3.0 (m, 2), 2.6 (m, 1 ), 2.2 (d, 1), 1.1 (br d, 3), 0.9 (br d, 3) ppm; (fraπs)-1 -((4-chloro-3-nitrophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 11 (br d, 1 ), 7.7 (m, 4), 7.3 (m, 3), 5.0 (q, 2), 4.7 (m, 0.5), 4.4 (m, 2.5), 3.8 (m, 0.5), 3.6-2.9 (m, 6), 1.4 (d, 1.5), 1.3 (d, 1.5) ppm; (frat7s)-1-((4-chloro-2-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (DMSO-d 6 ) 10.8 (br d, 1 ), 7.9-6.8 (m, 7), 5.1-2.8 (m, 10), 2.2 (s, 3), 1.3 (m, 6) ppm; (fra/7S)-1-((4-chloro-2-(diethylamino)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 2), 7.0 (t, 2), 6.8 (m, 3), 4.8 (br s, 3), 4 1 (br s, 1 ), 3.5 (q, 3), 3.2 (q, 4), 3.0 (br s, 1 ), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (br s, 3), 1 (m, 9) Ppm; (fraπs)-1-((4-chloro-2-hydroxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 2), 7.0-6.7 (m, 5), 4.9 (m, 0.5), 4.6 (br s, 2), 4.2 (m, 0.5), 3.6-3.2 (m, 3), 3.0 (br d, 1 ), 2.7 (br d, 1 ), 2.2 (d, 2), 1.3 (m, 3), 0.9 (m, 3) PPm; 1-((4-chloro-2-(hydroxymethyl)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 10.8 (d, 1 ), 7.7 (m, 2), 7.3 (m, 4), 6.9 (d, 1 ), 5.0-4.3 (m, 6), 3.9-2 9 (m, 7), 1.4 (d, 1.5), 1.2 (d, 1.5) ppm; (2R,5S)-1-((4-chloro-3-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 4), 7.0-6.7 (m, 3), 4.7 (m, 4), 4 1 (m, 1 ), 3.5 (m, 2.5), 3.2 (m, 0.5), 3.0 (s, 1 ), 2.7 (dd, 1 ), 2.2 (d, 1 ), 2.1 (m, 1 ), 1.2 (m, 3), 0 9 ( , 3) ppm; (frans)-1-((4-chioro-2-(ureιdomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (DMSO-d 6 ) 7.4 (m, 2), 7.1 (m, 4), 6.9 (d, 1 ), 6.4 (t, 1 ), 5.6 (s, 2), 5.0-4.0 (m, 4), 3.5 (m, 2), 3.3 (d, 2), 3.0 (m, 2), 2.2 (m, 2), 1.2 (br d , 3), 0.9 (br d, 3) ppm; 1-((4-chioro-2-amιnophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 11.2 (br d, 1 ), 7.7 (m, 2), 7.3 (t, 2), 6.9 (m, 3), 5.0-4.2 (m, 5), 3.9 (m, 1 ), 3.6 (m, 1 ), 3.4 (m, 1 ), 3.0 (m, 3), 1.4 (d, 1.5), 1.3 (d, 1.5) ppm; 1 -((4-chloro-3-amιnophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 11.2 (br d, 1 ), 7.8 (br s, 2), 7.3 (t, 2), 7.0 (d. 1 ), 6.4 (s, 1 ), 6.2 (d, 1 ), 4.8-4.2 (m, 5), 4.0 (m, 1 ), 3.6 (m, 1), 3.4 (d, 1 ), 3.2-2.9 (m, 4), 1.3 (m, 3) ppm; (2S)-1-((4-chioro-2-(ureido)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyi)piperazιne; NMR (CDCI 3 ) 9.0 (s, 1 ), 8.2 (s, 1 ), 7.3 (t, 1 ), 7.0 (t, 3), 6.8 (q, 3), 5.0 (s, 2), 4.6 (dt, 2), 4.4 (d, 0.5), 3.7 (br s, 0.5), 3.4 (m, 2.5), 3.0 (t, 0.5), 2.8 (m, 1), 2.6 (d, 1), 2.1 (m, 3), 1.4 (d, 1.5), 1.3 (d, 1.5) ppm; (2R)-1-((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)piperazιne; NMR (CDCI 3 ) 9.0 (s, 1 ), 8.2 (s, 1 ), 7.3 (t, 1 ), 7.0 (t, 3), 6.8 (q, 3), 5.0 (s, 2), 4.6 (dt, 2), 4.4 (d, 0.5), 3.7 (br s, 0.5), 3.4 (m, 2.5), 3.0 (t, 0.5), 2.8 (m, 1 ), 2.6 (d, 1 ), 2.1 (m, 3), 1.4 (d, 1.5), 1.3 (d, 1.5) ppm; (frans)-1-((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (DMSO-d 6 ) 10.8 (br s, 1 ), 8.2 (br s, 2), 7.8 (br s, 2), 7.7 (br s, 1 ), 7.3 (m, 2), 6.8 (br s , 2), 5.2-4.3 (m, 5), 3.9-3.1 (m, 5), 2.8 (t, 1 ), 1.5-1.1 (m, 6) ppm; (2R,5S)-1-((4-chloro-2-(ureido)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 9.0 (s, 1 ), 8.3 (s, 1 ), 7.3 (t, 1 ), 7.0 (t, 3), 6.8 (m, 3), 5.0 (s, 2), 4.6 (m, 2), 4.2 (d, 0.5), 3.7- 3.4 (m, 2.5), 3.2 (m, 2), 2.7 (d, 1 ), 2.5(m. 1 ), 2.2 (d, 1 ), 1.3 (br d, 3), 1.0 (br d, 3) ppm; (fraπs)-1-((4-bromo-2-formylpheπoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 10.4 (s, 1 ), 8.0 (s, 1 ), 7.6 (dd, 1 ), 7.3 (m, 2), 7.0 (m, 3), 4.8 (m, 3), 4.1 (br d, 1 ), 3.5 (m, 3), 3.0 (m, 1 ), 2.7 (dd, 1 ), 2.3 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; 1-((4-chioro-2-methoxycarbonyiphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 11.0 (br d, 1 ), 7.7 (m, 3), 7.6 (dd, 1 ), 7.3 (t, 2), 7.0 (d, 1 ), 5.0 (dq, 2), 4.7 (m, 1 ), 4.4 (m, 3), 3.8 (m, 4), 3.4 (m, 2), 3.0 (m, 2), 1.4 (d, 1.5 ), 1.2 (d, 1.5) ppm; (frat7s)-1-((4-chloro-2-methoxycarbonylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.9 (br s, 2), 7.8 (s, 1 ), 7.4 (m, 1 ), 7.1 (t, 2), 7.0 (d, 1 ), 4.8 (m, 3), 4.4 (m, 2), 3.9 (m, 4), 3.5 (m, 2), 2.8 (m, 2), 1.6 (m, 3), 1.3 (m, 3) ppm; 1-((4-chloro-2-aminocarbonylphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)piperazine; NMR (CDCI 3 ) 9.6 (br s, 1 ), 8.0 (s, 1 ), 7.6 (dd, 1 ), 7.4 (dd, 2), 7.2 (t, 2), 6.9 (d, 1 ), 5.0 (m, 3), 4.4 (m, 2), 4.0 (m, 1), 3.8 (m, 2), 3.6 (m, 1), 3.1 (m, 1), 2.9 (m, 1), 1.6 (d, 15), 14 (d, 1.5) ppm; 1-((4-chloro-2-(amιnocarbonyl)phenylamιno)methyi)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazme; NMR (DMSO-d 6 ) 11.2 (br s, 1 ), 7.9 (br s, 1 ), 7.7 (m, 3), 72 (m, 2), 6.6 (d, 1), 4.8 (brs, 1), 44-3.9 (m, 6), 34 (d, 1), 3.0 (m, 3), 1.4 (m, 3) ppm; (2R)-1-((4-chloro-2-amιnocarbonylphenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 9.1 (s, 1), 8.2 (s, 1), 7.4 (dd, 1), 7.3 (m, 3), 70 (t, 2), 6.8 (d, 1), 5.8 (brs, 1), 48 (m, 3), 3.5 (m, 3), 2.9 (d, 1), 2.7 (d, 1), 2.2 (m, 2), 14 (d, 1.5), 1.3 (d, 1.5) ppm; 1 -((4-chloro-2-formylphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 11.0 (brd, 1), 104 (s, 1), 76 (m, 4), 73 (t, 2), 7.2 (d, 1), 5.2 (m, 2), 47 (m, 1), 4.3 (m, 3), 3.9 (m, 1), 3.6 (m, 1), 3.1 (m, 3), 15 (d, 1.5), 1.3 (d, 15) ppm, (2R,5S)-1-((4-chloro-2-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 10.5 (s, 1), 7.8 (s, 1), 7.5 (d, 1), 73 (m, 2), 70 (t, 3), 4.8 (m, 3), 41 (m, 1), 3.5 (m, 3), 31 (brs, 1), 27 (dd, 1), 2.3 (dd, 1), 13 (m, 3), 09 (m, 3) ppm; (2R)-1-((4-chloro-2-formylphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 104 (s, 1), 7.8 (s, 1), 7.5 (d, 1), 73 (m, 2), 70 (t, 3), 48 (br s, 2), 47 (m, 1), 42 (m, 1), 34(m, 3), 31 (m, 1), 2.8 (brd, 1), 26 (br d, 1), 21 (m, 1), 20 (dd, 1), 13 (m, 3) ppm, (frans)-1-((4-chloro-2-cyanophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, NMR (CDCI 3 ) 7.5 (dd, 1), 7.3 (m, 2), 70 (m, 4), 48 (m, 3), 41 (m, 1), 35 (m, 3), 30 (m, 1), 2.7 (m, 1), 2.2 (m, 1), 1.3 (m, 3), 08 (m, 3) ppm; (frans)-1-((4-chloro-2-acetylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazme, NMR (DMSO-d 6 ) 10.8 (br d, 1), 7.8 (s, 2), 75 (m, 2), 7.3 (m, 3), 7.2 (m, 1), 53 (m, 1), 5.0 (s, 2), 4.3 (m, 3), 4.0 (m, 1), 3.8-33 ( , 2), 2.8 (m, 1), 2.6 (s, 3), 14 (dd, 3), 13 (m, 3) ppm; 1-((2-(acetylamιno)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 11.0 (br s, 1 ), 9.4 (s, 1 ), 8.0 (d, 1 ), 7.6 (d, 2), 7.3 (t, 2), 7.0 (m, 3), 49 (q, 2), 4.7 (m, 1), 4.3 (m, 3), 3.9 (m, 1), 3.6-2.8 (m, 4), 2.1 (s, 3), 1.4 (d, 1.5), 1.3 (d, 15) ppm, (frans)-1-((3-cyanophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 110 (br d, 1 ), 79 (s, 2), 75-73 (m, 6), 52 (d, 1 ), 49 (m, 2), 43 (m, 3) 36 (m, 2), 32 (m, 1), 2.8 (m, 1), 15-12 (m, 6) ppm, (2R,5S)-1-((3-hydroxy-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, NMR (DMSO-d 6 )105 (br d, 1 ), 93 (s, 1 ), 78 (s, 2), 72 (m, 2), 62(s, 2), 61 (s, 1), 47(m, 4), 43 (m, 3), 38 (m, 1), 36 (m, 1), 2.8 (m, 1), 22 (s, 3), 14 (m, 3), 12 (m, 3) ppm, (frans)-1-((4-methyl-2-ammophenoxy)methyl)carbonyI-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, NMR (DMSO-d 6 ) 110 (br m, 1 ), 78 (s, 2), 72 (m, 5), 53 (m, 1), 50 (m, 2), 43 (m, 3), 40 (m, 1), 35 (m, 2), 28 (m, 1), 22 (s, 3), 13 (m, 6) ppm (fraπs)-1-((3-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 )110(brd, 1), 100(s, 1), 79 (s, 2), 75 (m, 2), 73 (m, 3), 69 (m, 1), 52 (m 1 ), 49 (m, 2), 43 (m, 3), 40 (m, 1 ), 36 (m, 2), 28 (m, 1 ), 13 (m, 6) ppm, (frans)-1-((4-methyl-2-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, NMR (CDCI 3 ) 75 (s, 1), 73( m, 3), 70 (t, 2), 68 (d, 1), 47 (m, 3), 42 (br d, 1), 36 (m, 1), 35 (q, 2), 30 (br s, 1), 27 (m, 4), 22 (m, 4), 13 (m, 3), 09 (m, 3) ppm, (frans)-1-((2-methoxycarbonylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, NMR (CDCI 3 ) 121 (s, 1) 78 (m, 3), 73 (brs, 1), 70 (brs 4) 48 (m, 2), 43 (m, 3), 39 (m, 5), 36 (m 1) 28 (m 1) 24(m, 1), 16 (m 3), 13 ( 3) ppm, (frans)-1 -((3-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne NMR (DMSO-d 6 )108(brd, 1), 78 (m, 3), 77 (m, 1).76 (t, 1), 74(d, 1), 73 (t, 2), 52 (m, 1) 50 (m, 2), 47 (m, 1), 43 (m, 3), 40 (m, 1), 36 (m, 1), 28 (m, 1), 14 (m, 3), 13 ( , 3) ppm, (frans)-1-((4-acetyl-2-(aminocarbonyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme, NMR (DMSO-d 6 ) 97 (brd, 1), 86 (s, 1), 85 (s, 1), 81 (d 1), 78(s, 1), 76 (brs, 3), 73 (t, 3), 54(d, 1), 51 (m, 2), 46 (m, 1), 43 (s, 2), 42 (m, 1), 37 (m, 1), 34 (m, 1), 30 (m, 1), 26 (s, 3), 14 (m, 3), 12 (m, 3) ppm, (frans)-1-((4-nιtro-3-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 1 1.2 (br d, 1 ), 8.0 (m, 3), 7.3 (m, 2), 7.0 (m, 2), 5.3 (d, 1 ), 5.0 (m, 2), 4.3 (m, 3), 3.7-3.3 (m, 2), 3.0 (m, 1 ), 2.8 (m, 1 ), 2.6 (s, 3), 1.4 (m, 3), 1.3 (m, 3) ppm; (fraπs)-1-((5-nitro-2-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)piperazιne; NMR (DMSO-d 6 ) 10.5 (br d, 1 ), 7.7 (m, 4), 7.4 (d, 1 ), 7.3 (t, 2), 5.3 (d, 1 ), 5.1 (m, 2), 4.7 (m, 1 ), 4.3 (m, 2), 3.9 (q, 1 ), 3.6 (br d, 1 ), 3.4 (m, 1 ), 2.9 (dd, 1), 2.3 (s, 3), 1 4 (m, 3), 1.3 (m, 3) ppm; (frans)-1-((4-amιno-3-nitrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 1 1.2 (br d, 1 ), 7.9 (t, 2), 7.3 (m, 4), 7.0 (d, 1 ), 4.8 (m, 3), 4.3 (m, 3), 3.9 (m, 1 ), 3.6 (m, 1 ), 3.2 (m, 1 ), 2.8 (t, 1 ), 1 4 (dd, 3), 1.3 (dd, 3) ppm; (frans)-1-((5-nitro-2-aminophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazme, NMR (DMSO-d 6 ) 1 1.2 (br d, 1 ), 7.9 (t, 2), 7 7 (d, 1 ), 7.6 (s, 1 ), 7.3 (t, 2), 6.7 (d, 1 ), 5 0 (m, 3), 4.7 (m, 1), 4.3 (m, 2), 4.0 (q, 1 ), 3.6 (m, 1 ), 3.3 (m, 1 ), 2.8 (t, 1 ), 1 4 (dd, 3), 1.3 (dd, 3) ppm; (frans)-1 -((2-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)piperazιπe, NMR (DMSO-d 6 ) 11.3 (m, 1 ), 7.9 (br s, 2), 7.8 (br m, 1 ), 7.3 (m, 4), 7.0 (t, 1 ), 5.3 (m, 1 ), 5.0 (m, 2), 4.6 (m, 1 ), 4.3 (m, 2), 3.6 (m, 3), 2.8 (m, 1 ), 1.3 (m, 6) ppm; (fraπs)-1 -((3-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 10.5 (br d, 1 ), 7.8 (s, 2), 7.3 (m, 2), 7.1 (t, 1 ), 6 5 (m, 3), 4.8 (m, 2), 4.3 (m, 3), 3.8 (m, 1 ), 3.6 (m, 1 ), 3.4 (m, 2), 2.8 (t, 1 ), 1 4 (m, 3), 1 2 (m, 3) ppm; (fraπs)-1-((4-methoxy-2-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine;; NMR (DMSO-d 6 ) 1 1.2 (br s, 1 ), 7.9 (br s, 2), 7.3 (m, 3), 7 1 (s, 2), 5.2 (d, 1 ), 4.9 (s, 2), 4.3 (m, 3), 3.9-3 4 (m, 9), 2.8 (m, 1 ), 1 4-1.2 (m, 6) ppm, (frans)-1-((5-methoxy-2-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (DMSO-d 6 ) 1 1.2 (br d, 1 ), 7.9 (dd, 2), 7.6 (m, 1 ), 7 3 (t, 2), 6.6 (q, 2), 5.3 (d, 1 ), 5.0 (s, 2), 4.3 (m, 3), 3.8 (s, 3), 3 4 (m, 3), 2.8 (m, 1 ), 2.6 (s, 3), 1.5- 1.2 (m, 6) ppm; (fraπs)-1-((2-((2-hydroxyethyl)amιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (DMSO-d 6 ) 10.8 (br d, 1 ), 9.1 (br s, 1 ), 7.9 (d, 1 ), 7.8 (br s, 2), 7.4 (t, 1 ), 7.2 (m, 3), 7.0 (t, 1 ), 5.2 (d, 1 ), 5.0 (m, 2), 4.3 (m, 3), 3.9-3.4 (m, 7), 2.8 (dd, 1 ), 1.4-1.2 (m, 6) ppm; (frans)-1-((2-((2-hydroxyethoxy)carbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, NMR (DMSO-d 6 ) 10 0 (br s), 7 7 (m, 3), 7 4 (t, 1 ), 7 3 (t, 2), 7 0 (dd, 2), 5 0 (m, 2), 4 5 (m, 1 ), 4 2 (m, 5), 3 8 (q, 1 ), 3 6 (t, 2), 3 4 (m, 2), 2 9 (m, 1 ), 1 3 (m, 3), 1 2 (m, 3) ppm, (frans)-1-((2-(2-hydroxyethoxy)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, NMR (DMSO-d 6 ) 10 5 (br d, 1 ), 7 8 (t, 2), 7 3 (t, 2), 6 9 (m, 4), 4 8 (m, 3), 4 4 (m, 1 ), 4 3 (m, 2), 3 9 (m, 3), 3 6 (m, 3), 3 4 (m, 1 ), 2 8 (m, 1 ), 1 4 (m, 3), 1 2 (m, 3) ppm, (frans)-1-((2-acetyl-4,5-dιmethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, NMR (DMSO-d 6 ) 10 4 (br s, 1 ), 7 8 (m, 2), 7 4 (s, 1 ), 7 2 (t, 2), 6 8 (m, 1 ), 5 2 (d, 1 ), 4 9 (s, 2), 4 3 (m, 3), 3 8 (m, 1 ), 3 6 (m, 1 ), 3 4 (m, 1 ), 2 8 (m, 1 ), 2 6 (s, 3), 2 2 (s, 3), 2 1 (s, 3), 1 4 (m, 3), 1 2 (m, 3) ppm, (frans)-1-((5-methoxy-2-(methoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, NMR (DMSO-d 6 ) 11 0 (br d, 1 ), 7 9 (br s, 2), 7 7 (d, 1 ), 7 3 (m, 2), 6 6 (m, 2), 5 0 (m, 3), 4 3 mi, 3), 3 8 (s, 3), 3 7 (s, 3), 3 6 (m, 1 ), 3 4 (m, 2), 2 8 (dd, 1 ) 1 4 (dd, 3), 1 2 (dd, 3) ppm, 1 -((4-chlorophenylamιno)methyl)carbonyl-2-methyl-4-(4-fluorobenzyi)pιperazιne, NMR (DMSO- d 6 ) 7 4 (t, 2), 7 15 (t, 2), 7 1 (d, 2), 6 6 (d, 2), 5 8 (t, 1 ), 4 5 (m, 1 ), 4 2 (m, 1 ), 3 9 (m, 1 ) 3 7 (m, 1 ), 3 4 (m, 1 ), 3 3 (m, 1 ), 2 9 (m, 1 ), 2 8 (d, 1 ), 2 6 (d, 1 ), 2 0 (m, 2), 1 3 (d 1 5) 1 1 (d, 1 5) ppm, (frans)-1-((benzo[b]pyran-2-on-7-yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, NMR (CDCI 3 ) 7 6 (d, 1 ), 7 4 (d, 1 ), 7 3 (m, 2), 7 0 (m, 3) 6 8 (s, 1 ), 6 3 (d, 1 ), 4 7 (m, 3), 4 1 (m, 1 ), 3 6 (m, 3), 3 0 (br s, 1 ), 2 7 (br d, 1 ), 2 2 (d, 1 ) 1 3 (m, 3), 1 0 (m, 3) ppm, (fransJ-1-((2-chloro-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((1-nιtroso-3,6-dι(hydroxysulfonyl)naphthalen-2-yloxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne, frat7sj-1-((2-πιtroso-4-hydroxysulfonylnaphthalen-1-yioxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans -1-((3,6-dι(hydroxysulfonyl)naphthalen-1-yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fra/7S ) -1-((3-hydroxysulfonyl-6-amιnonaphthalen-1-yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fraπs / ) -1-((3-hydroxysulfonyl-7-amιnonaphthalen-1-yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ('frans)-1-((5-hydroxysulfonylquιnolιn-8-yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrans / ) -1-((2,3-dιnιtro-7-hydroxysulfonylnaphthalen-1-yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ("fraπsJ-1-((2-carboxy-4-hydroxysulfonylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ffrans 1-((2-amino-4-hydroxysulfonylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; (trans)-l -((4-formyl-2,6-dι-f-butyiphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrans ) -1-((4-(morpholιn-4-yl)methyl-2,5-dιmethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, ('frans / )-1-((4-(methoxycarbonyl)-2,6-dιchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frans / ) -1-((4-(hydroxysulfonyl)naphthalen-1-yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrans / ) -1-((3,6-di(hydoxysulfonyl)-8-aminonaphthalen-1-yloxy)methyl)carbonyl-2,5-dimethyl-4- (4-fluorobenzyl)pιperazιne, frans / )-1-((2-carboxy-5-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ffrans 1-((4-trifluromethyl-2 I 3,5,6 ) -tetrafluorophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans / ) -1-((2-methoxy-4-formyl-5-(2-hydroxy-3-methoxy-5-formylphenyl)- phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; { , fraπs)-1-((4-carboxy-2,3,5,6-tetrafluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((4-(adamant-1-yl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans -1-((2-(adamant-1-yl)-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans -1-((2,4-dι((1-methyl-1-phenyl)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('fransJ-1-((2-acetyl-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (ftans 1-((2-nitro-4-f-butylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine (trans)-! -((2-acetyl-4-chloro-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, fΛans / )-1-((2-acetyl-4-chloro-6-nιtrophenxoy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((2-acetyl-4,6-dιbromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans / )-1-((2-formyl-4,6-dι(f-butyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frat7S y )-1-((3,5-dinitrophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazme frans / )-1-((2,6-dιchloro-4-ethoxycarbonylpheπoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ( , frans / )-1-((2-ethoxycarbonyl-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans / )-1-((2-methoxy-6-(prop-3-enyl)phenoxy )methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans / )-1-((3-fluoro-4-cyanophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans y )-1-((2-acetyl-4-methyl-6-nitrophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme, ('frans)-1-((2-methylbenzothιazol-5-yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaziπe, (fraπs / )-1-((2-carboxy-4-(hydroxysulfonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, frans / )-1-((4-(4-(tπfluoromethyl)phenoxy)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans -1-((2-(1/-/-pyrazol-3-yl)-4-chloro-5-methylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-(1H-pyrazol-3-yl)-4-chlorophenoxy )methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frans / )-1-(((2-phenyl-4-oxo-7-hydroxy-4H-1-benzopyran-3-yl)oxy)methyl)carbonyl-2,5-dιmethyl- 4-(4-fluorobenzyl)pιperazιne; ('fraπs 1-((2-chloro-3-trifluoromethyiphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fraπs)-1-((2-methoxy-4-(butoxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; ('frans / )-1-((6-hydroxyquιnolin-2-yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans)-1-((2-methoxycarbonyl-6-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frans / )-1-((2,5-di(f-butyl)-4-methoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; (?rans)-1-((2-formyl-4-methyiphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fΛans / )-1-((2-(2/-/-benzotrιazol-2-yl)-4-(2-hydroxyethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; (trans)-! -((4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2-(methylthio)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffrans / )-1-((3,5-di(f-butyl)-4-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((3, 5-dibromo-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans 1 -((2,6-diιodo-4-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fransJ-1-((2-nitro-4-methoxycarbonyiphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fransj-1-((2-(ethoxycarbonyl)indol-5-yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; ffrans y )-1-((3-(2-carboxyethyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fransJ-1-((2,6-dinitro-4-(carboxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; (trans)-! -((2-nιtro-3-carboxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)pιperazιne; ('fransJ-1-((6-carboxynaphthalen-2-yloxy)methyl)carbonyl-2 I 5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2,6-difluoro-4-ethylcarbonylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; (ϊransJ-1-((2-(2-(methoxycarbonyl)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ( , frat)s)-1-((2-(prop-3-enyl)-4-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans / )-1-(((3-oxo-2H- benzofuran-6-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ('frans -1-((2,4,6-tπbromo-3,5-dιmethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fransj-1 -((4-(heptylcarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ffransj-1-((2-carboxy-4-acetylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-nιtro-4-phenylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fraπs 1-((2-methoxy-4-(eth-2-enyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffraπs -1-((2-chloro-4-methoxycarbonylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; (fraπsj-1 -((2,6-diιodo-4-cyanophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frans)-1-((2,6-dιιodo-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (fraπs -1-(((2-phenyl-4-oxo-4/-/-1-benzopyran-5-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ( , frans)-1-(((2-phenyl-4-oxo-7-methoxy-4H-1-benzopyran-5-yl)oxy)methyl)carbonyl-2,5-dιmethyl- 4-(4-fluorobenzyl)pιperazιne; fraπs>1-(((2-phenyl-4-oxo-7-methoxy-2,3-dιhydro-4/-/-1-benzopyran-5-yl)oxy)methyl)carbonyl- 2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((4-octylcarbonylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -(((4-phthalιmιd-1 -ylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (fraπsJ-1-((3-(morpholιn-4-yl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((3-chloro-4-bromophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('frans / )-1 -(((2-oxo-7-methoxy-2/-/-1-benzopyran-8-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, fraπs / )-1-((2-acetyl-5-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne I (frans)-1-((2-(1-methylcyclohex-1-yl )-4-methyl-6-(2-hydroxy-3-(1 -methylcyclohex-1-yl)-5- methylbenzyl)phenoxy)methyi)carbonyl-2.5-dιmethyl-4-(4-fluorobenzyl)pιperazιne (ftans / )-1-((2-formyl-3-methoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fraπs / )-1-((2-amιno-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ('frans / )-1-((2-chloro-4-carboxy-6-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrans y )-1-((2,6-dιmethyl-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffraπs y )-1-((2-methoxy-4-(2-(carboxy)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frar7s 1-((2,6-dιmethoxy-4-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; (trans)-! -((2, 6-dibromo-4-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fransJ-1-((2-nitro-4-(ethoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans)-1-((2-amιno-4-(methoxycarbonyl)phenoxy)methyi)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ( , frans / )-1-((4-(2-(4-nitrophenyl)eth-2-enyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fransJ-1-((2-acetyl-3,5-dimethoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; ffrans / )-1-((2,6-dι(f-butyl)-4-(methoxycarbony0phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-methoxy-4-(ethoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; fraπsJ-1-((2-cyclohexyl-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (trans)-! -((2, 6-dιmethyi-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frans / )-1-((2-methoxy-4-ethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ( , frans y )-1-((4-n-butylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans 1-(((3-carboxy-1-bromonaphthalen-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans / )-1-((2-bromo-4-nιtro-6-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-formyl-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffrans)-1-((2,6-dichloro-4-(ethoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs -1-(((4-methyl-2-oxo-2 -/-1-benzopyran-6-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; fftans / )-1-((2,3-dibromo-4-formyl-6-methoxyphenoxy)methyi)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; frans -1-((4-(2-(4-nιtrophenyl)eth-2-yl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2,4, 6-tπbromo-3-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (fransj-1 -((2-benzyl-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ( , frans)-1-((2-(bezothiazol-2-yl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, ('frans / )-1-((2-nιtro-6-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, ('fransJ-1-((2-ethoxy-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyi-4-(4- fluorobenzyOpiperazine, ( , fraπs / )-1-((2-bromo-4,6-dι(f-butyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frat7sJ-1-((2-(pyrroiιdιn-1-yl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, fransJ-1-((2-(morpholιn-4-yl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, fraπs -1-((2-(pιperιdιn-1-yl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans / )-1-((2-formyl-4-chloro-6-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans / )-1-(((4,7-dimethoxy-5-formylbenzofuran-6-yl)oxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; frat7s -1-(((2-oxo-4-methyl-8-nιtro-2H-1-benzopyran-7-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; (fransj-1 -((2-methoxy-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frar?s)-1-((2-chloro-4-bromo-6-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; frans / )-1-((2,4-dιmethyl-6-f-butylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, frans / )-1-(((2-nitro-4-(hydroxysulfonyl)naphthalen-1-yl)oxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme, ('fraπsJ-1-(((3-(hydroxysulfonyl)-6-amιnonaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrans 1-(((3-(hydroxysulfonyl)-7-amιnonaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ('frans)-1-(((3-(methoxycarbonyl)naphthalen-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (fransJ-1-((2-carboxy-4-(hydroxysulfonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (YransJ-1-((4-n-butylcarbonylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((3-ethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-(((2-ethyl)hexoxy)carbonyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; (frans / )-1-((4-((n-pentoxy)carbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ffrans -1-((2-nιtro-5-(methoxycarbonyl)phenoxy)methyl)carbonyl-2 5-dιmethyl-4-(4- fluorobenzyOpiperazme; ('frans -1-((2,4,6-tribromo-3-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs -1 -((2-methoxy-5-methyiphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans / )-1-((3-methoxy-4-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans -1-((4-(2-(phenyl)eth-2-enyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((4-(1 ,2,4-tπazol-1 -yl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; ('f_-at7s)-1-((2-nιtro-4-chloro-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; ('frans 1-((4-(n-hexoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans / )-1-((2-chloro-4-formyl-6-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; frans / )-1-((2-methoxy-4-(2-(ethoxycarbonyl)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (trans)-! -((2,3,4, 6-tetrachlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frar7s / )-1-((2-((2-methylpropoxy)carbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans ) -1-((2-(n-butoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (fransJ-1-((4-(phenylammo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, fraπs)-1-((2-hydroxymethyl-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (trans)-! -((2-mercaptophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne (fransJ-1-((2-nιtro-6-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans / )-1-((2,4-dι(1-methylbutyl)phenoxy)methyl)carDonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (fraπsJ-1-((3-tπfluoromethyl-4-nιtrophenoxyjmethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ('frans / )-1-((2,6-dιbromo-4-(methoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπsJ-1-((2,4-dιchloro-6-acetyl)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπs -1-((2-methoxycarbonyi-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; frans -1-((2-formyl-4-bromo-6-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frat7s 1-((2,6-dιformyl-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, frar)s)-1-((2,6-dιnιtro-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frans / )-1-((2-nιtro-4-acetylphenoxy)methyl)carboπyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, frans -1-((2-formyl-4-nιtro-6-methoxyphenoxy)methyl)carbonyI-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, frans / )-1-((4-(amιnocarbonyl)methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (fransJ-1 -((2-methoxycarbonyl-4-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, ('fraπs / )-1-(((2-phenyl-4-oxo-4/-/-1-benzopyran-6-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ( , frans 1-((2-chloro-4-tnfluoromethylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, ('fransJ-1-((2-carboxy-3-methyl-6-ιsopropytphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (trans)-! -(((5, 7-dιbromo-2-methylquιnolιn-8-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (fransJ-1-(((5,7-dιchloro-2-methylquιnoiιn-8-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, frans)-1-((2,6-dιnιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffrans / )-1-((2-nιtro-4-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, frans -1-((2-amιno-4-(1 ,1-dιmethylpropyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans -1-((2,6-dιphenyl-4-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fraπs)-1-((2,4-dιchloro-3-methyl-6-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frat7sJ-1-(((2-oxo-4-(carboxy)methyl-2H-1-benzopyran-7-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; ffransJ-1-(((2-oxo-4-tπfluoromethyl-2H-1-benzopyran-7-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; ('frans / )-1-((2-f-butyl-4-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frans)-1-((2-formyl-6-methylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((2-methoxycarbonyl-4-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-bromo-5-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frat7s y )-1-((2,4-dι(1 ,1-dιmethylpropyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((3-methyl-4-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans / )-1-((2,3,4-tπfluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frat7s / )-1-((2,5-dιfluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fra/7s)-1-((2-methyl-5-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, fraπs -1-(((2-methyl-3-(ethoxycarbonyl)ιndol-5-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; frans y )-1-((2-amιnocarbonyl-4-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; ('frans 1-((2,6-dιnιtro-3-f-butylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; fraπs)-1-((2-fluoro-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans -1-((2-carboxy-3-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffransj-1-((2-(2-ethylhexoxy)carbonylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-!-(( 2,4,6-tπbromo-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fra/7s / )-1-((4-(4-bromophenyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπsj-1 -((4-(4-carboxypheπy)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ( , frans -1-((2,3,6-tπfluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, fransJ-1-((2,4,5-tπfluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2,4, 6-trifluorophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, frans / )-1-((2-fluoro-5-tπfluoromethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; Cfrans -1-(((2,4-dιnιtronaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -(((3, 6-dι(hydroxysulfonyl)-8-amιnonaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; (trans)-! -((2-acetyl-4-chiorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fransJ-1-((2,6-dιmethyl-4-(1-(3,5-dιmethyl-4-hydoxyphenyl)-1- methylethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans / )-1-((4-(3-(4-hydroxyphenyl)hex-2-yl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans / .-1-(((6-(hydroxysuifonyl)naphthalen-2-yl)oxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fraπsJ-1-((2-chloro-4-methylphenoxy)methy0carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans -1-((2-bromo-4,5-difluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrat7sJ-1-((2-chloro-4-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans / )-1-((2-methoxy-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ( , frans)-1-((4-(2-(methoxycarbony)ethyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans y )-1-((2,6-dιphenyl-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, frans y ) -1-((2-amιno-3-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((2-methyl-4-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2-methyl-4-ιodophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffrans)-1-((2-fluoro-6-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (frans / ) -1-((2-carboxy-3-ιsopropyl-6-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frans / )-1-((2-carboxy-3,4,6-tπchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (7rans -1-((2-carboxy-6-isopropylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, (frans / )-1-((2-(piperidin-1-yl)-4-methylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -(((2, 3-dιhydro-2,2-dιmethyibenzofuran-7-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, ('frans / )-1-((2,6-di(f-butyl)-4-(1-methylpropyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, ffrat7s / )-1-((3-methyl-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (trans)-! -(((phenanthren-9-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, fransJ-1-((2-nitro-4-bromophenoxy)methyi)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, frans / )-1-((2-fluoro-3-tπfluoromethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e, ('frans)-1-((2-nιtro-5-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans / )-1-((2-chloro-4-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans / )-1-((2-formyl-4-bromo-6-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, fraπs)-1-((2-methoxy-4-(acetyl)methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrans 1-((4-(5-mercaptotetrazol-1-y0phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ftans / )-1-((2,4,6-trnodo-3-(2-carboxy)butylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme, ( , frans 1-((3-hydroxymethyl-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (trans)-! -((2,3, 5,6-tetrafluoro-4-(2, 3,4, 5,6-pentafluorophenyl)phenoxy)methyl)carbonyl-2, 5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fraπs)-1-((2-(benzotrιazol-2-yl)-4,6-dι(1 ,1-dιmethylpropyl)phenoxy)methyi)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans / )-1-((2-phenyl-3-hydroxy-4-oxo-4/-/-1-benzopyran-6-yl)oxy)methyl)carbonyl-2,5-dιmethyl- 4-(4-fluorobenzyl)pιperazιne, (trans)-! -((ιndanonyl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans 1-((2-nιtro-4-(hydroxysulfonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (trans)-! -((2-nιtro-3-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπs -1-((4-(2,4-dιnιtrophenyl)amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, fransj-1-((3-methyl-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2, 6-dιbromo-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans -1-((2,6-dιιodo-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2-formyl-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffrat7s -1-((2-amιno-5-nιtrophenoxy)methy0carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fransj-1 -((2-amιno-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-amιno-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans)-1-((2-amιno-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (fransJ-1-((2-amino-4-f-butylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazme, (fransJ-1-((2-amιno-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fransJ-1-((2-methyl-3-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs / ) -1-((2-carboxy-5-amιnophenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (trans)-! -((3-methyl-4-amιnophenoxy)methyl)carboπyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ffransj-1-((2,5-dιmethyl-4-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2, 6-dιbromo-4-amιnophenoxy)methyl)carbonyl-2, 5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans -1-((2-carboxy-4-aminophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme, CfransJ-1-((2-amιnocarbonylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans 1 -((2-amιnocarbonyl-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frat7s / )-1-((4-(2-amιnoethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans 1-((2,4,6-trι(dιmethylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((2-hydroxymethyl-6-methoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((2, 3-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4- 4-fluorobenzyi)pιperazιne, (frarjs)-1-((4-(methoxycarbonyl)-5-methoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((2-methoxy-4-(methoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2, 6-dιmethoxy-4-(prop-3-enyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fransJ-1-((2-acetyl-5-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (ftaπs)-1-((2-acetyl-4-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ('fraπsJ-1-((2-acetyl-3-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; frans / ) -1-((2-methoxy-4-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((2, 6-dιmethoxy-4-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; frans)-1-((2,6-dι(f-butyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2,4-dι(f-butyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fraπs / )-1-((3,5-dι(f-butyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans / )-1-((2,6-dι(ιsopropyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans 1-((2-methoxy-4-(ethoxycarbony)methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; frans / )-1-((2-ethoxy-5-prop-2-enylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, frans -1 -((2-methoxy-5-prop-2-enylphenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraA7s -1-((2,6-dι(1-methylpropyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; frans / )-1-((2,4-dιfluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, (trans)-! -((2, 6-dιphenylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, fraπs 1-((2-nιtro-3-trifluoromethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-cyclopentyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, (trans)-! -((4-cyclopentylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2,3-difluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans / )-1-((2-carboxy-6-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrans ) -1-((2-amιno-4-chloro-5-nitrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frans -1-((3,4-difluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans^-1-((2-carboxy-6-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frat3s / ) -1-((2,4-dιcarboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; ('frans)-1-((2,3-dιmethoxy-5-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frans -1-((2-bromo-4-fluorophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, (trans)-! -((2, 6-dιchoro-4-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ffrans)-1-((3-methyl-4-isopropylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -(((fluoren-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; (trans)-! -((2-diethylamιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; (trans)-! -((2-amιno-3-nitrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -(((2-oxo-3,4,8-tπmethyl-2/-/-1-beπzopyran-7-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffra/7s / )-1-((2-acetyl-4-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans / )-1-((2-fluoro-4-bromophenoxy)methyi)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, frat7s / )-1-((2-(methylcarbonyl)amιno-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fraπs -1-(((1-acetylnaphthalen-2-yl)oxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('frans)-1-((2-methoxy-4-nitrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffransJ-1-((3-methyl-5-isopropylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; frat7s / )-1-((2-methyl-4-formyiphenoxy)methyt)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans -1-(((1-amιnonaphthalen-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans / )-1-((4-amιnonaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fra 7s -1-((2-methoxy-4-(1 ,2-dιhydroxyethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (fransJ-1-(((3-(2-amιnoethyl)ιndoiιn-5-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frans / )-1-(((5-chloroquinolin-8-yl)oxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, fransJ-1-((2-methoxy-4-(2-(amιno)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ('fransJ-1-((4-(2-(amιno)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frans / )-1-((2-methoxy-4-(2-(amιno)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans -1-((2,4-dιamιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans -1-((4-amιnophenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ( , fraπs / )-1-((2-(dιethylamιno)methyl-4-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ('frans y )-1-((2-methyl-5-(2-amιnobutyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fransJ-1-((2-(benzotrιazol-2-yl)-4-(1 ,1 ,3,3-tetramethylbutyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((2-nιtro-4-bromo-6-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-iodophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans -1-((2-(2-carboxyethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ffraπs -1-((2-carboxy-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fransJ-1-((2,6-dιbromo-3-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fransJ-1-((2,6-dichioro-3-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frat7s / )-1-((2-methoxy-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans / )-1-((2,6-dιmethoxy-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ( , fraπs y )-1-((4-(2-carboxyethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ('frans y )-1-((2-(2-hydroxyethyl)phenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((3-(2-hydroxyethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ('frans)-1-((4-(2-hydroxyethyl)phenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('f ans / )-1-((2-methoxy-4-(2-hydroxyethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('ftaπs)-1-((2,4-dιbromo-6-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-fluoro-6-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ( , frat7sj-1-((2,4-dιchloro-6-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans -1-((2,4-dιιodo-6-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans)-1-((2-methoxy-6-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffraπs / )-1-((2-ethoxy-6-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frat7Sj-1-((2-formyl-5-(dιethylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; frans / )-1-((2-formyl-5-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (frans -1-((2-formyl-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e, frat7s)-1-((2-formyl-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frat7s 1-((2-formyl-4-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, frans)-1-(((4-methoxynapthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (ϊraπsJ-1-((2-carboxy-5,6-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((3-nιtro-4-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -(((fluoren-9-on-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, fraπs;-1-(((4-hydroxy-1 ,2,3,4-tetrahydronaphthalen-8-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((2, 3,4,5, 6-pentabromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans ) -1-((2-methyl-3,4,5,6-tetrabromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fraπs / ) -1-((2,3,4-trιchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπs 1-((2-methyl-4-bromo-6-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; (trans)-! -((2-chloro-4-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2, 4, 6-tπιodophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne 1 frans / ) -1-((2-formyl-4-chlorophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, (trans)-! -((3-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffrat7s)-1-(((1-bromonaphthaien-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; CfransJ-1-(((1 ,6-dιbromonapthalen-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, fraπsJ-1-(((1-nιtrosonaphthalen-2-yl)oxy)methyt)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frat7s -1-(((2,4-dιchloronaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrat7s -1-(((2-nιtronaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frat7s 1-(((2-carboxynaphthaten-1-yi)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; fra/7s -1-(((2-methylnaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; frans / )-1-(((3-(hydroxysuifonyl)-7-(dιmethylamιno)naphthalen-1-yl)oxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frat7s -1-(((4-methoxynaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, frans / )-1-(((1-formylnapthalen-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (fraπsJ-1-(((1-carboxynaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans -1-(((1-amιno-4-(hydroxysulfonyl)naphthalen-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fransJ-1-((4-(naphthalen-2-yl)amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frat7s)-1-(((3-amιnonaphthalen-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans -1-((2-fluoro-4-(carboxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans -1-((2-chloro-4-(carboxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, ffrans)-1-((2-methoxy-4-(carboxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, fransJ-1-((4-hydroxymethylphenxoy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffransJ-1-((2-(hydroxymethyl)-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans -1-((2,6-dι(hydroxymethyl)-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (trans)-! -((2-methoxy-4-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, ('fransJ-1-((4-mercaptophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffrans -1-(((2-carboxyιndol-5-y0oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffransJ-1-(((3-carboxyιndol-5-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -(((ιndol-4-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, fraπs / )-1-(((ιndol-5-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((2-(benzoxazol-2-yl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (frans -1-(((2-methylquιnolιn-8-yl)oxy)methyl)carDonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ( , fransJ-1-(((5,7-dιbromoquιnolιn-8-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobeπzyOpiperazine, (trans)-! -(((5, 7-dιιodoquιnolιn-8-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -(((5-nιtroquιnolιn-8-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -(((quιnolιn-5-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffrans / )-1-(((5-(hydroxysulfonyl)-7-iodoquinolin-8-yl)oxy)methyl)carDonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, (fransJ-1-(((2-phenyl-4-oxo-4/-/-1-benzopyran-7-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ffratιs 1-((2-carboxy-2,5,7,8-tetramethyl-2,3-dιhydro-1-benzopyran-6-yi)oxy)methyl)carbonyl- 2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fra/7S)-1-(((2-oxo-3-chloro-4-methyl-2H-1-benzopyran-7-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne, (frans y ) -1-(((2-oxo-3-(diethylamino)methyl)-4-methyl-2/-/-1-benzopyran-7-yl)oxy)methyl)carbonyl- 2,5-dιmethyi-4-(4-fluorobenzyl)pιperazιne; ('frans -1-(((2-oxo-6-methoxy-2H-1-benzopyran-7-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans -1-(((2-oxo-2/-/-1-benzopyran-7-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fraπs 1-((2-methoxy-4-formyl-6-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobeπzyOpiperazine; (frans -1-((2-methoxy-4-formyl-6-ιodophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-methoxy-4-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (YransJ-1-((2-ethoxy-4-formyiphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; frans -1-((2-carboxy-4-formylphenox)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frans / ) -1-((2,4-dιchloro-6-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fratJS / )-1-((2,4-dιnιtro-6-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; ffrans)-1-((2,4-dιnιtro-6-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((2,4-dιnιtro-6-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrat7s / )-1-((2,5-dιnιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('f/-aπs / )-1-((2-nιtro-5-methytphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frat7s / )-1-((2-nitro-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2,4-dιnιtrophenoxy)methyt)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frat7sJ-1-((2-nιtro-4-formylphenoxy)methy0carbonyl-2,5-dιmethyl-4-(4-fluorobenzy0pιperazιne, ('fransJ-1-((2-nitro-4-formyl-6-methoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((2-nιtro-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans)-1-((2-nιtro-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, ('frat7sJ-1-((2,6-dιnιtro-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; ('frans)-1-((2-nιtro-4-(carboxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frat7s)-1-((2,6-dιchlorophenoxy)methy0carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, (frans 1-((3-methoxy-5-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans / )-1-((4-cyanophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans y )-1-((4-(1-methyl-1-phenylethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans 1-((3-(ethyiamιno)-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, ('frans -1-(((2-acetylnaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, ( , frans / )-1-((2-(carboxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e, ( , frat7s -1-((4-(carboxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans / )-1-(((benzotrιazol-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans / )-1-(((quιnolιn-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((4-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ( ' frat7sJ-1-((2,6-dιmethoxy-4-formyiphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frat7s)-1-((3,4-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans / )-1-((2,4,6-tri(f-butyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frat7s)-1-((2,6-dιmethoxy-4-(methoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e, (frans 1 -((3-tπfluoromethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (fransJ-1-((2-methyl-5-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, ('fraA7s / )-1-((4-(4-cyanophenyl)phenoxy)methyl)carbonyi-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((3-nιtro-4-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans / )-1-((3-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffrans y )-1-((4-methylphenox)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, ('frans / )-1-((4-(methoxycarbonyl)methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, frans -1-(((carbazol-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -(((2-oxo-1 ,3-benzothιol-2-on-6-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, frans / )-1-(((2-pheπyl-4-oxo-4/-/-1-benzopyran-3-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -(( (2-oxo-4-methyl-2H-1 -benzopyran-7-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, frans)-1-((4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fransj-1-((3-carboxy-4-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frans -1-((2-methoxy-5-amιnophenoxy)methyt)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans / )-1-(((2-phenyl-4-oxo-2,3-dιhydro-4H-1-benzopyran-6-yl)oxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffrat7s;-1-(((quιnolιn-6-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fraπs)-1-((2,3-dιamιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fraπs)-1-((4-(hydroxysuifonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)- 1-(((fluorenon-9-on-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1-(((5,6,7,8-tetrahydronaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (trans)- 1 -(((5,6,7, 8-tetrahydronaphthalen-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)- 1-((2,4,6-trιbromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1-((2,6-dιbromo-4-cyanophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (trans)- 1-((2-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1 -((2,3,5, 6-tetrafluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)- 1-((2,6-dιfluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1-((2,3-dιchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1-((2,3,6-tπchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1-((2-chloro-4,5-dιmethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)- 1-((2,5-dιchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1-((2-chloro-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)- 1-((2-(methylcarbonyl)amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)- 1-((2-ιsopropoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1-((2-(benzyloxy)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1-((2-ethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1-((2-phenylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1-((2-(methoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fl uorobenzyOpiperazine; (trans)- 1-((2-(ethoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fl uorobenzyOpiperazine; (trans)- 1-((2-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)- 1-((2-(ethylcarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2-(f-buty0phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fraπsJ-1-((2-ιsopropylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans / )-1-((2-(1-methylpropyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; (frans -1-((2,3-dimethylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, ('frans -1-((2,3,5-trιmethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frat7s,)-1-((2,3,6-trimethylphenxoy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzy0piperazine, ffrar)s / ) -1-((2,4-dιmethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans / ) -1-((2,4,6-trimethoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, fransJ-1-((2-methyl-5-ιsopropylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans y ) -1-((2,5-dιmethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fraπs -1-((2,5-dιmethyl-4-(dιethylamιno)methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (fransJ-1-((2-(f-butyl)-6-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans / ) -1-((2,6-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffraπs)-1-((2-prop-3-enyl-6-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e, (frans / ) -1-((2-prop-2-enylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans -1-((2-ethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, ('frans-)-1-((2-n-propylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((3-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffraπs / ) -1-((3,5-dιfluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans -1-((3-chloro-4-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((3, 5-dιchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, fraπs)-1-((3-ιodophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((3-(phenylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((3-(dιethylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, ('frar.s;-1-((3-phenylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ( , frans y )-1-((3-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; (trans)-! -((3-tπfluoromethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((3-f-butylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((3-ιsopropylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, fransJ-1-((3-methyl-4-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fra/ιs 1-((3,4-dιmethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyt)pιperazιne, frans / )-1-((2-f-butyl-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, fransJ-1-((2-ιsopropyl-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((3-ethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, fratJs-)-1-((2,6-dιmethyl-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (fraπs 1-((2,6-dιbromo-4-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans 1-((2-bromo-4-chloropheπoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (ϊransj-1 -((2-methyl-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('fraπs 1-((2-ιsopropyl-4-chloro-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, fraπs)-1-((4-(methylcarbonyl)amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frans -1-((4-ethoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, (trans)-! -((4-propoxyphenoxy)methyt)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne (trans)-! -((4-t?-butoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((4-t7-hexoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne (trans)-! -((4-t7-heptoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans / )-1-((4-(propoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((4-(ethylcarbony0phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, Cfraπs / )-1-((4-(1 l 1 ,3,3-tetramethylbutyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fransJ-1-((4-(1 ,1-dιmethylpropyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; frans)-1-((4-(1-methylpropyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frans 1-((2-methoxy-4-methylphenoxy)methy0carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; ('frans y )-1-((2-acetyl-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; f ans 1-((2-(f-butyl)-4-methylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; ('frans / )-1-((3-(ethylamιno)-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyi-4-(4- fluorobenzyOpiperazine; ('frans ; )-1-((4-(methoxycarbonyl)methylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((4-ethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans / )-1-((4-n-propyiphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fraA7sJ-1-((2-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fraπsJ-1-((2-carboxy-4,6-dιbromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans y )-1-((2-carboxy-4,6-dιchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fransj-1-((2-carboxy-4,6-dιιodophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fransJ-1-((2-carboxy-6-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fraπs)-1-((2-carboxy-6-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans 1-((2-carboxy-5-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fraπs -1-((2-carboxy-5-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frans 1-((2-carboxy-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((2-carboxy-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans 1-((2-carboxy-4-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fransJ-1-((2-carboxy-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((2-carboxy-4-ιodophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffraπs / )-1-((2-carboxy-4-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιπe, (trans)-! -((2,3,4-tπchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobeπzyl)pιperazιne, (trans)-! -((2,3,4, 5,6-pentachlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (trans)-! -((2,4, 5-tπchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπsJ-1-((3-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne (frans -1-((3-(methoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('frat7s)-1-((3-(ethoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans / )-1-((2,6-dιmethyl-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans 1-((3,5-dιmethyl-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans 1-((3-methyl-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans)-1-((2-ιsopropyl-4-chloro-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, fraπs -1-((4-ethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frat7s)-1-((2-(f-butyl)-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((3-formyl-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans)-1-((2-methoxy-4-prop-3-enylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans / ) -1-((2-(1-phenyethyl)-4-chtorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, fraπs ) -1-((4-(ethoxycarbonyl)methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((4-tπfluoromethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((3-fluoro-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2-fluoro-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ( raπsJ-1-(((7-methoxynaphthalen-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fransj-1 -((2-benzyloxy-4-cyanophenoxy)methyl)carbonyl-2,5-dtmethyl-4-(4- fluorobenzyOpiperazine, frans -1-((2-chloro-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fraπs -1-((2-bromo-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrans -1-((3,5-dιmethoxy-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((2,6-dιbromo-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frat7S -1-((4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((3-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frat7s)-1-((2-methyl-3-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fraπs / )-1-((3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, ('fraπsj-1-((2-nιtro-3-carboxy-6-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frat7s)-1-((3-cyanophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans)-1-((2-methoxy-5-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fftans / )-1-((2-nitro-5-carboxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, (frans)-1-((3-(carboxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-methoxy-5-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans y )-1-((4-(dιmethylamιno)methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs / )-1-((4-(2-(dιmethylamιno)ethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((3-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -(((naphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fransJ-1-(((5-amιnonaphthalen-1-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frat7s)-1-((3-nιtro-4-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frat7sJ-1-((2,6-dι(f-butyl)-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, frans / )-1-((3-carboxy-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans)-1-((2-methyl-5-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((2-nιtro-4-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((4-(benzyloxy)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-(amιnocarbonyl)phenoxy)methy0carbonyl-2,5-dιmethyl-4-(4- fiuorobenzyOpiperazine; frat7s -1-((3,5-dι(trifluoromethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((2,4-dιbromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans)-1-((2,6-dιbromo-4-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (trans)-! -((2,4-dιchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frat7s / )-1-((3-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans)-1-((3,5-dιmethyl-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; frat7s / )-1-((3,5-dιcarboxyphenoxy)methy0carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fransJ-1-((2-chloro-4-carboxyphenoxy)methy0carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine, ('frans)-1-((2,6-dιchloro-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frans)-1-(((2-carboxyquιnolιn-4-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2,6-dιmethyl-4-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('fAaπsJ-1-((2,6-dι(f-butyl)-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, ( , fraπs / )-1-((2-amιno-5-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (f ans;-1-((2,6-dι(f-butyl)-4-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frans / )-1-(((4-carboxyquinolin-2-yl)oxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((3-nιtro-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans)-1-((3-ethyl-4-chloro-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((3, 5-dι(methoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffrans)-1-((2-(morpholιn-4-yi)methyl-4-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine, (fraπsJ-1-((2-methoxy-4-cyanophenoxy)methyi)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('frat7s y )-1-((2-chloro-4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ( , ft-at7S 1-((2-trifluoromethylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)pιperazιne; ffraπs / )-1-((2-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazine; ( , frans -1-((2-methyl-4-acetylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fraπsJ-1-((3-(dιmethylamιno)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fraπs / )-1-((3-methyl-4-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((3, 5-dimethylphenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((4-phenylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; (fraπs y )-1-((4-(ethoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fra/?s / )-1-((4-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; (frar7S)-1-((4-benzylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)piperazιne, ('frans)-1-((2-methoxy-4-carboxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('fransj-1-(((3-carboxynaphthalen-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans > )-1-((2-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans -1-(((quιnoiin-8-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; (trans)-! -((3-aminophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazιne; ffrans y )-1-((4-(aminocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (ftaπsJ-1-((3,5-dimethoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)pιperazιne; ('frans)-1-((2-(cyclohexyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)pιperazιne, ('frans)-1-(((quιnolin-6-y0oxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazιne; frans)-1-((2,4-dιchloro-3-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2,5-dιmethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((3-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (ft-at-s / )-1-((3-(methylcarbonyl)amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; fransj-1-((3-acetylphenoxy)methy0carbonyl-2,5-dιmethyi-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((3-trifluoromethylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, frans)-1-((4-bromophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans / )-1-((2-methoxy-5-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -(((tropιnon-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, ffratJs -1-((2-nιtro-5-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ( , frans / )-1-((2-nitro-5-formylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazme, ffΛatJs / )-1-((3-formyl-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans -1-((2-carboxy-5-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((2-amιno-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, frans)-1-((2-amιno-3-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, ('frat7s / )-1-((2-nιtro-4-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιπe, ('frat7s)-1-((2,6-dιchloro-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)pιperazιne; (trans)-! -((3-fluoro-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ( , frans)-1-((2,3-difluoro-6-nitrophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; frans y )-1-((2-chloro-4-nitrophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, ('frat3s > )-1-((2-nitro-4-cyanophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, frans 1-((2-bromo-4-methylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('frans / )-1-((3-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzy0pιperazιne, (trans)-! -((3,4-dιchlorophenoxy)methy0carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('fra/ιs)-1-((3,5-dιchlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((3,4,5-tπmethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, (trans)-! -((4-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ffrat7sJ-1-((3,5-dιmethyl-4-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fraπs / )-1-((4-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, Cfrat7s ) -1-((4-(methoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((4-tπfluoromethylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans / ) -1-((4-f-butylphenoxy)methy0carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((4-ιsopropylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans)-1-(((naphthalen-2-yl)oxy)methy0carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, ('frans -1-(((6-bromonaphthalen-2-yl)oxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('fratιs / ) -1-((3-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ffraπs 1-((2-methoxy-5-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -(((! ,3-benzodιoxolan-5-yl)oxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ('frans / )-1-((2,6-dιmethyl-4-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((2-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans / )-1-((2-methoxy-4-(amιno)methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans / )-1-((3-(amιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- ffluorobenzyOpiperazine; ('fransj-1-((3-(methoxycarbonyl)methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; ( , ft-ans)-1-((2-(4-phenylcarbonyl)-4-fluorophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('frans)-1-((2-(1-methyl)cyclohexyl-2,4-dimethylphenoxy)methyi)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((2-(benzyloxycarbonyi)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ( , fra/7s -1-((2-(4-(methyl)phenylcarbonyl)-5-methoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; frans -1-((2-phenylcarbonyl-5-octoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((4-octyiphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine; frans / )-1-((2-(2-(carboxy)phenylcarbonyl-5-di(n-butyl)aminophenoxy)methyl)carbonyl-2,5- dimethyl-4-(4-fluorobenzyl)piperazine; ('ftans 1-((2-phenylcarbonyl-5-methoxyphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ffrans 1-((2-methoxy-4-(3-hydroxyprop-2-enyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ffraπs)-1-(((3-(phenylaminocarbony0naphthalen-2-yl)oxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('fraπsJ-1-(((6-(phenyicarbonyl)naphthalen-2-yl)oxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fransJ-1-((2-((2-phenylethyl)carbonyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; fraπs 1-((4-((4-fluorophenyl)carbonyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('frans / )-1-((2-(phenylamino)carbonyiphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ffrans / )-1-((2-phenylcarbonylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans 1-((2-phenylcarbonyl-4-chloro-5-methyiphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; frans ) -1-((4-(4-chlorophenyl)carbonylphenoxy)methy0carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('frans y )-1-((4-benzylcarbonyl)p enoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans / )-1-((2-phenylcarbonyl-4-methyiphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('fransJ-1-((4-(2-methylcarbonylethyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; ('frat7S / )-1-((4-phenylcarbonylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; and fraπsJ-1-((3-phenylcarbonylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine. C. In a similar manner, the following compounds of formula (lb) were made: 1-((3,4,5-trimethoxyphenoxy)methyl)carbonyl-4-(benzyl)piperazine; NMR (CDCI 3 ) 7.6 (m, 3), 7.5 (m, 4), 6.2 (s, 2), 4.6 (m, 4), 4.2 (m, 4), 3.8 (m, 9), 3.4 (m, 1 ), 2.6 (m, 1 ) ppm; 1-((3-methoxyphenoxy)methyl)carbonyl-4-(benzyl)piperazine; NMR (CDCI 3 ) 7.3 (m, 5), 6.5 (m, 4), 4.6 (s, 2), 3.8-3.5 (m, 9), 2.4 (m, 4) ppm; 1-((3,4-dimethoxyphenoxy)methyl)carbonyl-4-(benzyl)piperazine; NMR (CDCI 3 ) 7.8 (m, 2), 7.4 (m, 3), 6.8 (d, 1 ), 6.6 (d, 1 ), 6.4 (dd, 1 ), 4.8 (d, 2), 4.3 (m, 3), 4.0 (m, 1 ), 3.7 (s, 3), 3.65 (s, 3), 3.6-3.3 (m, 8), 3.2-2.9 (m, 3) ppm; 1 -((phenoxy)methyl)carbonyl-4-(benzyl)piperazine and 1 -(chioro)acetyl-4-(benzyl)piperazine; NMR (CDCI 3 ) 7.3 (m, 7), 7.0 (m, 3), 4.7 (s, 2), 3.6 (m, 6), 2.4 (m, 4) ppm; 1-((4-chlorophenoxy)methyl)carbonyl-4-(benzyl)piperazine and 1-(chloro)acetyl-4- (benzyl)piperazine; NMR (CDCI 3 ) 7.3 (m, 7), 6.9 (m, 2), 4.6 (s, 2), 3.6 (m, 6), 2.4 (m, 4) ppm; 1-((3-cyanophenoxy)methyl)carbonyl-4-(benzyl)piperazine; NMR (CDCI 3 ) 7.3 (m, 2), 7.0 (m, 4), 6.8 (m, 3), 4.4 (q, 2), 4.2 (d, 1 ), 3.9 (d, 2), 3.6 (m, 3), 3.0 (m, 3), 2.6 (m, 2) ppm; 1-((4-cyanophenoxy)methyl)carbonyl-4-(benzyl)piperazine; NMR (CDCI 3 ) 7.6 (m, 4), 7.4 (m, 3), 7.0 (d, 2), 4.9 (q, 2), 4.6 (d, 1 ), 4.3 (d, 2), 4.0 (d, 2), 3.6 (t, 1 ), 3.4 (d, 2), 3.0 (m, 2) ppm; 1-((3-(1-methyiimidazolin-2yl)phenoxy)methy0carbonyl-4-(benzyl)piperazine; NMR (CDCI 3 ) 7.5 (m, 6), 7.2 (m, 3), 5.0 (d, 2), 4.0 (m, 4), 3.3 (q, 4), 3.0 (m, 6) ppm; -((4-chloro-2-amιnocarbonylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 8.7 (s, 1 ), 7.8 (s, 1 ), 7.7 (s, 1 ), 7.6 (dd, 1 ), 7.4 (q, 3), 7.2 (d, 1 ), 5.0 (s, 2), 3 4 (br d, 4), 3.3 (s, 2), 2 4 (br d, 4) ppm; -((5-chloroquιnolιn-8-yloxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 9 0 (s, 1 ), 8.5 (d, 1 ), 7.75 (dd, 1 ), 7.65 (d, 1 ), 7 4 (q, 2), 7.1 (d, 1 ), 5.1 (s, 2), 3.5 (m, 6), 2 4 (br d, 4) ppm; -((3-trιfluoromethoxyphenoxy)methyl)carbonyl-4-(benzyl)pιperazιne; -(3-(3,4,5-tπmethoxyphenoxy)propyl)carbonyl-4-(benzyl)pιperazιne; -(1-(3,4,5-tπmethoxyphenoxy)propyl)carbonyl-4-(benzyl)pιperazιne, -(1 -(3,4,5-trιmethoxyphenoxy)pentyl)carbonyl-4-(benzyl)pιperazιne, -((4-methoxyphenoxy)methyl)carbonyl-4-(benzyl)pιperazιne; -((3,5-dιmethoxyphenoxy)methyl)carbonyl-4-(benzyl)pιperazιne; -((3-chlorophenoxy)methyl)carbonyl-4-(benzyl)pιperazιne; -(1-(3,4,5-trιmethoxyphenoxy)ethyl)carbonyl-4-(benzyl)pιperazιne; -((3,4-dιchlorophenoxy)methyl)carbonyl-4-(benzyl)pιperazιne, -((3,5-dιchlorophenoxy)methyl)carbonyl-4-(benzyi)pιperazιne; -((3,4,5-trιmethylphenoxy)methyl)carbonyl-4-(benzyl)pιperazιne, -((4-nιtrophenoxy)methyi)carbonyl-4-(benzyl)pιperazιne, -(1-(3,4,5-tπmethoxyphenoxy)septyl)carbonyl-4-(benzyl)pιperazιne, -(1-(3,4,5-trimethoxyphenoxy)-2-methylpropyOcarbonyl-4-(benzyl)piperazine, -(1-(3,4,5-tπmethoxyphenoxy)butyl)carbonyl-4-(benzyl)pιperazιne, -((4-bromophenoxy)methyl)carbonyl-4-(benzyi)pιperazιne; -((4-fluorophenoxy)methyl)carbonyl-4-(benzyl)pιperazιne, -((4-tπfluoromethylphenoxy)methyl)carbonyl-4-(benzyl)pιperazιne, -(((4-chlorophenyl)thιo)methyl)carbonyl-4-(benzyl)pιperazιne, -((2-chlorophenoxy)methyl)carbonyl-4-(benzy pιperazιne, -((4-(benzyloxy)phenoxy)methyl)carbonyl-4-(benzyl)pιperazιne, -((4-(methoxycarbony phenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((4-(amιno)phenoxy)methyl)carbonyl-4-(benzyl)pιperazιne; -((4-hydroxyphenoxy)methyl)carbonyl-4-(benzyl)pιperazιne; -((4-(1-methylethyl)phenoxy)methyl)carbonyl-4-(benzyθpιperazιne, -((4-(2,2-dimethylethyl)phenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((4-(acetyl)phenoxy)methy0carbonyl-4-(benzyl)piperazine; -((napthalenyl-2-oxy)methyl)carbonyl-4-(benzyl)piperazine; -((4-chloro-3,5-dimethylphenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((1 ,3-benzodioxolyl-5-oxy)methyl)carbonyl-4-(benzyl)piperazine; -((2,4,6-trichlorophenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((2,3,4,5,6-pentafluorophenoxy)methyl)carbonyl-4-(benzyi)piperazine; -((2-(benzyloxy)-4-cyanophenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((2-chloro-4-bromophenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((3-bromophenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((3,5-tπfluoromethylphenoxy)methyl)carbonyl-4-(benzyl)piperazine; -(((5-0X0-6, 7, 8-trihydronaphthalen-1-yl)oxy)methyl)carbonyl-4-(benzyl)piperazine; -(((2-oxo-2H-1-benzopyran-4-yl)oxy)methy)carbonyl-4-(benzyl)piperazine; -((2-cyanophenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((4-methyl-3,5-dibromophenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((quinoiinyl-6-oxy)methyl)carbonyl-4-(benzyl)piperazine; -(((diphenyl)methoxy)methyl)carbonyl-4-(benzyl)piperazine; -((3-(moφholin-4-yl)phenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((2-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine, hydrochloride salt; -((pyπdinyl-3-oxy)methyl)carbonyl-4-(benzyl)piperazine; -((2-(beπzyl)phenoxy)methyi)carbonyl-4-(benzyl)piperazine; -((4-(benzy0phenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((4-(formyl)phenoxy)methyl)carbonyl-4-(benzyl)piperazine; -((2-(prop-3-enyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,6-dibromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((benzothiazolyl-2-oxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-cyclohexylphenoxy)methyl)carbonyl-4-(4-chiorobenzyl)piperazine; -((4-(benzyloxy)carbonylphenoxy)methyi)carbonyl-4-(4-chlorobenzyl)piperazine; -((5-chloroquinolinyl-8-oxy)methyl)carbonyl-4-(4-chlorobenzy0piperazine; -((4-(imidazol-1-yl)phenoxy)methy0carbonyl-4-(4-chlorobenzyl)piperazine; -((3-chloro-5-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-carboxyphenoxy)methyl)carbonyl-4-(benzyl)pιperazιne; -((4-ιodophenoxy)methyl)carbonyl~d-(4-chlorobenzyl)pιperazιne, hydrochloride salt, NMR (DMSO-d 6 ) 7.6 (m, 6), 6.8 (d, 2), 4.9 (d, 2), 4 4 (m, 3), 4.0 (m, 1 ), 3.6 (m, 1 ), 3 4-2 9 (m, 6) ppm, -((2-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2,6-dιmethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methylquιnolιnyl-4-oxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -(((2,3-dιhydro-1 /-/-ιnden-5-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((coumaπn-4-yloxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((4-chlorobenzyloxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -(((4-chlorophenyl)amιno)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, hydrochloride salt, NMR (DMSO-d 6 ) 1 1 4 (br s, 1 ), 7.6 (dd, 4), 7.1 (d, 2), 6.6 (d, 2), 4 4 (m, 4), 4 0 (m, 4), 3.6-2.9 (m, 4) ppm; -((4-chloronaphthalenyl-1-oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((4-chlorophenyl)(methyl)amιno)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -(((di(4-chloro)phenyl)methoxy)methyl)carbonyl-4-(chlorobenzyl)piperazine, -((3,5-dιmethoxy-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, NMR (CDCI 3 ) 7.2 (q, 4), 6.2 (s, 2), 4 7 (s, 2), 3.9 (s, 6), 3.6 (m, 4), 3.5 (s, 2), 2 4 ( , 4) ppm; -((5,7-dιchloroquιnolιnyl-8-oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((6-hydroxycoumaπn-4-yloxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-fluoro-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, hydrochloride salt, NMR (DMSO-dβ) 11.8 (s, 1 ), 7.5 (m, 5), 7.1 (d, 1 ), 6.8 (d, 1 ), 5.0 (q, 2), 4.3 (m, 3), 3 9 (m, 1 ), 3.6-2.9 (m, 6) ppm; -((2-(hydroxymethyl)phenoxy)methyl)carbonyi-4-(4-chlorobenzyl)pιperazιne; -((2,4-dιbromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2,4-dιchlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((4-chloro-3-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 7 6 (m, 6), 7.3 (d, 1 ), 5.0 (q, 2), 4.3 (m, 3), 3.9 (m, 1 ), 3.5-2.9 (m, 6) ppm; -((4-bromo-2-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 11.4 (br s, 1 ), 7.8 (m, 2), 7.5 (m, 4), 7.2 (d, 1 ), 5.2 (q, 2), 4 4 (m, 3), 4.0 (m, 1 ), 3.6-2.9 (m, 6) ppm; -((2-methoxy-5-nitrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((4-bromo-2-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne hydrochloride salt, -((2-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne hydrochloride salt; -((3,5-dιmethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne hydrochloride salt; -((2-amιnocarbonyl-4-chlorophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 8.7 (br s, 1 ), 7.8 (s, 1 ), 7 7 (s, 1 ), 7.6 (dd, 1 ), 7.2 (m, 3), 7.2 (d, 1 ), 5.0 (s, 2), 3.5 (m, 6), 2.4 (m, 4) ppm; -((3,5-dιmethoxy-4-bromophenoxy)methyl)carboπyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 6.2 (s, 2), 4.7 (s, 2), 3.9 (s, 6), 3.6 (m, 4), 3.5(s, 2), 2.4 (m, 4) ppm, -((3-formyl-4-nitrophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCl 3 ) 10.5 (s, 1 ), 8.2 (d, 1 ), 7.3 (m, 6), 4.9 (s, 2), 3.6 (m, 2), 3.5 (m, 4), 2.4 (m, 4) ppm; -((2-chloro-4-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((1-nιtroso-3,6-di(hydroxysulfonyl)naphthalen-2-yloxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazine; -((2-nιtroso-4-hydroxysulfonylnaphthalen-1-yloxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme; -((3,6-dι(hydroxysulfonyl)naphthalen-1-yloxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-hydroxysulfonyl-6-amιnonaphthalen-1-yloxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -((3-hydroxysulfonyl-7-amιnonaphthalen-1-yloxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((5-hydroxysulfonylquinolin-8-yloxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2,3-dιnιtro-7-hydroxysulfonylnaphthalen-1-yloxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazine; -((2-carboxy-4-hydroxysulfonylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-amιno-4-hydroxysuifonylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((4-formyl-2,6-di-f-butylphenoxy)methyl)carbonyl-4-(4-chlorobenzyi)piperazιne; -((4-(morpholin-4-y0methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; -((4-(methoxycarbonyl)-2,6-dichlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-(hydroxysulfonyl)naphthalen-1-yloxy)methyi)carbonyl-4-(4-chlorobenzyl)pιperazine; -((3,6-dι(hydoxysulfonyl)-8-amιnonaphthaien-1-yloxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme, -((2-carboxy-5-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-tπfluromethyl-2,3,5,6,-tetrafluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methoxy-4-formyl-5-(2-hydroxy-3-methoxy-5-formylphenyl)phenoxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme, -((4-carboxy-2,3,5,6-tetrafluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-(adamant-1-yl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -((2-(adamant-1-yl)-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,4-dι((1 -methyl-1-phenyl)ethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-acetyl-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -((2-nιtro-4-f-butylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-acetyl-4-chloro-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-acetyl-4-chloro-6-nιtrophenxoy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-acetyl-4,6-dιbromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-formyl-4,6-dι(f-butyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3,5-dιnιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιchloro-4-ethoxycarbonylphenoxy)methyl)carbonyl-4-(4-chtorobenzyl)pιperazιne, -((2-ethoxycarbonyl-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methoxy-6-(prop-3-enyl)phenoxy )methyl)carbonyl-4-(4-chlorobenzyt)pιperazιne, -((3-fluoro-4-cyanophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-acetyl-4-methyl-6-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methylbenzothιazol-5-yloxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-carboxy-4-(hydroxysulfonyl)phenoxy)methyl)carbonyi-4-(4-chiorobenzyl)pιperazιne, -((4-(4-(tπfluoromethyl)phenoxy)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-(1 /-/-pyrazol-3-yl)-4-chloro-5-methylphenoxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme, -((2-(1 H-pyrazol-3-yl)-4-chlorophenoxy )methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((2-phenyl-4-oxo-7-hydroxy-4/-/-1-benzopyran-3-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme, -((2-chloro-3-tπfluoromethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-methoxy-4-(butoxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((6-hydroxyquinolin-2-yloxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-methoxycarbonyl-6-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,5-di(f-butyl)-4-methoxyphenoxy)methyi)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-formyl-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-(2H-benzotriazol-2-yl)-4-(2-hydroxyethyl)phenoxy)methyl)carbonyl-4-(4- chlorobenzyl)piperazine; ((4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-(methylthio)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((3,5-di(f-butyl)-4-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((3,5-dibromo-4-methylphenoxy)methyi)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,6-diiodo-4-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-nitro-4-methoxycarbonylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-(ethoxycarbonyl)indol-5-yloxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((3-(2-carboxyethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,6-dinitro-4-(carboxymethyl)phenoxy)methyt)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-nitro-3-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((6-carboxynaphthaien-2-yioxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,6-difluoro-4-ethylcarbonylphenoxy)methyl)carbonyl-4-(4-chlorobenzyt)piperazine; ((2-(2-(methoxycarbonyl)ethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-(prop-3-enyl)-4-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; (((3-oxo-2H- benzofuran-6-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,4,6-tribromo-3,5-dimethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyt)piperazine; ((4-(heptylcarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-carboxy-4-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyi)piperazine; ((2-nitro-4-phenylphenoxy)methyl)carbonyl-4-(4-chiorobenzyl)piperazine; ((2-methoxy-4-(eth-2-enyl)p enoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-chloro-4-methoxycarbonylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,6-diiodo-4-cyanophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; •((2,6-diiodo-4-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyi)piperazine; ■(((2-phenyl-4-oxo-4/-/-1-benzopyran-5-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyt)piperazine; -(((2-phenyl-4-oxo-7-methoxy-4H-1-benzopyran-5-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazine, -(((2-phenyl-4-oxo-7-methoxy-2,3-dιhydro-4/-/-1-benzopyran-5-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme, -((4-octylcarbonylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((4-phthalιmιd-1-ylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-(morpholιn-4-yl)phenoxy)methyl)carbonyl-4-(4-chiorobenzyl)pιperazιne, -((3-chloro-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((2-oxo-7-methoxy-2H-1-benzopyran-8-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne -((2-acetyl-5-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-( 1 -methylcyclohex-1 -yl )-4-methyl-6-(2-hydroxy-3-( 1 -methylcyclohex-1 -yl)-5- methylbenzyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-formyl-3-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-amιno-4-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-chloro-4-carboxy-6-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιmethyl-4-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methoxy-4-(2-(carboxy)ethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιmethoxy-4-(hydroxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιbromo-4-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -((2-nιtro-4-(ethoxycarbonyl)pheπoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-amιno-4-(methoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -((4-(2-(4-nιtrophenyl)eth-2-enyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne -((2-acetyl-3,5-dιmethoxyphenoxy)methyl)carbonyl-4-(4-chtorobenzyi)pιperazιne, -((2,6-di(f-but-yl)-4-(methoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine -((2-methoxy-4-(ethoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-cyclohexyl-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιmethyl-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methoxy-4-ethylphenoxy)methyi)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-n-butylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((3-carboxy-1-bromonaphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-bromo-4-nιtro-6-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-formyl-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2,6-dιchloro-4-(ethoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((4-methyl-2-oxo-2/-/-1-benzopyran-6-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,3-dιbromo-4-formyl-6-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-(2-(4-nιtrophenyl)eth-2-yl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne > -((2,4,6-tπbromo-3-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-benzyl-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-(bezothιazol-2-yl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-nιtro-6-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-ethoxy-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-bromo-4,6-dι(f-butyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-(pyrrolιdιn-1-yl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-(morpholιn-4-yl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-(pιpeπdιn-1-yl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-formyl-4-chloro-6-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((4,7-dιmethoxy-5-formylbenzofuran-6-yl)oxy)methyl)carbonyl-4-(4-chiorobenzyl)pιperazιne, -(((2-oxo-4-methyl-8-nιtro-2H-1-benzopyran-7-yl)oxy)methyl)carboπyl-4-(4- chlorobenzyOpiperazme; -((2-methoxy-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιπe, -((2-chloro-4-bromo-6-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,4-dιmethyl-6-f-butylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((2-nιtro-4-(hydroxysulfonyl)naphthalen-1-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme; -(((3-(hydroxysulfonyl)-6-amιnonaphthalen-1-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme; -(((3-(hydroxysulfonyl)-7-amιnonaphthalen-1-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperaz e; -(((3-(methoxycarbonyl)naphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -((2-carboxy-4-(hydroxysulfonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((4-π-butylcarbonytphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((3-ethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ■ ((4-(((2-ethy0hexoxy)carbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((4-((n-pentoxy)carbonyl)phenoxy)methyl)carboπyl-4-(4-chlorobenzyl)pιperazιne; ((2-nιtro-5-(methoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2,4,6-tribromo-3-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ■ ((2-methoxy-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; •((3-methoxy-4-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((4-(2-(phenyl)eth-2-enyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; ((4-(1 ,2,4-triazol-1-yl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-nιtro-4-chloro-5-methylphenoxy)methyi)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((4-(π-hexoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-chloro-4-formyl-6-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-methoxy-4-(2-(ethoxycarbonyl)ethy0phenoxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazine; ((2,3,4,6-tetrachlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-((2-methylpropoxy)carbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-(n-butoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((4-(phenylamιno)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-hydroxymethyl-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-mercaptophenoxy)methyl)carbonyl-4-(4-chlorobenzyt)pιperazιne; ((2-nιtro-6-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2,4-dι(1-methylbutyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((3-trιfluoromethyl-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2,6-dιbromo-4-(methoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2,4-dιchloro-6-acetyl)methyt)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-methoxycarbonyl-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-formyl-4-bromo-6-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2,6-diformyl-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2,6-dinιtro-4-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazine; ((2-nitro-4-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; ((2-formyl-4-nitro-6-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((4-(amιnocarbonyt)methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; -((2-methoxycarbonyl-4-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -(((2-phenyl-4-oxo-4/-/-1-benzopyran-6-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -((2-chloro-4-trifluoromethylphenoxy)methyi)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-carboxy-3-methyl-6-ιsopropylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; -(((5,7-dibromo-2-methylquιnoiιn-8-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -(((5,7-dichloro-2-methylquιnoiin-8-yi)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2,6-dinitrophenoxy)methyl)carbonyl-4-(4-chlorobeπzyl)pιperazιne; -((2-nιtro-4-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-amιno-4-(1 ,1-dιmethylpropyt)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιphenyl-4-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,4-dιchloro-3-methyl-6-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((2-oxo-4-(carboxy)methyl-2H-1-beπzopyran-7-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazine; -(((2-oxo-4-trifluoromethyl-2/-/-1-benzopyran-7-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme; -((2-f-butyl-4-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-formyl-6-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-methoxycarbonyl-4-acetylphenoxy)methyi)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-bromo-5-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2,4-dι(1 ,1-dιmethylpropyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-methyl-4-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,3,4-trifluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2,5-difluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-methyl-5-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -(((2-methyl-3-(ethoxycarbonyl)ιndol-5-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-amιnocarbonyl-4-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2,6-dιnitro-3-f-butylphenoxy)methyl)carboπyl-4-(4-chlorobenzyl)piperazine; -((2-fluoro-4-nitrophenoxy)methyl)carbonyl-4-(4-chlorobenzyi)piperazine; -((2-carboxy-3-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazine; -((2-(2-ethylhexoxy)carbonylphenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -(( 2,4,6-trιbromo-4-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazine, -((4-(4-bromophenyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-(4-carboxypheny)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,3,6-trιfluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,4,5-trifluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine, -((2,4,6-tπfluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-fluoro-5-tπfluoromethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((2,4-dιnιtronaphthalen-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((3,6-dι(hydroxysulfonyl)-8-amιnonaphthalen-1-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme, -((2-acetyl-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιmethyl-4-(1-(3,5-dιmethyl-4-hydoxyphenyl)-1-methylethyl)phenoxy)methyl)carbonyl-4- (4-chlorobenzyl)pιperazιne, -((4-(3-(4-hydroxyphenyl)hex-2-yl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((6-(hydroxysulfonyl)naphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-chloro-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-bromo-4,5-dιfluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-chloro-4-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methoxy-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-(2-(methoxycarbony)ethyl)phenoxy)methyl)carboπyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιphenyl-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-amιno-3-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methyl-4-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methyl-4-ιodophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-fluoro-6-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-carboxy-3-ιsopropyl-6-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-carboxy-3,4,6-trιchlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-carboxy-6-ιsopropylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-(pιpeπdιn-1-yl)-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((2,3-dιhydro-2,2-dιmethylbenzofuran-7-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιπe, -((2,6-dι(f-buty0-4-(1-methylpropyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-methyl-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((phenanthren-9-yi)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-nιtro-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-fluoro-3-tπfluoromethytphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-nιtro-5-methoxyphenoxy)methyl)carbonyl-4-(4-chtorobenzyl)pιperazιne, -((2-chloro-4-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-formyl-4-bromo-6-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methoxy-4-(acetyl)methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-(5-mercaptotetrazol-1-yl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,4,6-trιιodo-3-(2-carboxy)butyiphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-hydroxymethyl-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,3,5, 6-tetrafluoro-4-(2, 3,4,5, 6-pentafluorophenyl)phenoxy)methyl)carDonyl-4-(4- chlorobenzyOpiperazme, -((2-(benzotπazol-2-yl)-4,6-dι(1 ,1-dιmethylpropyl)phenoxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazine, -((2-phenyl-3-hydroxy-4-oxo-4H-1-benzopyran-6-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme, -((ιndanonyl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-nιtro-4-(hydroxysulfonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -((2-nιtro-3-methytphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-(2,4-dιnιtrophenyl)amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-methyl-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobeπzyl)pιperazιne, -((2,6-dιbromo-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιιodo-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -((2-formyl-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobeπzyl)pιperazιne, -((2-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, -((2-amιno-5-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-amιno-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-amιno-4-chlorophenoxy)methyl)carbonyl-4-(4-chiorobenzyi)pιperazιne, -((2-amιno-4-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-amιno-4-f-butylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-amιno-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, ((2-methyl-3-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-carboxy-5-amιnophenoxy)methyi)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((3-methyl-4-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2,5-dιmethyl-4-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2,6-dιbromo-4-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-carboxy-4-amιnophenoxy)methyl)carbonyl-4-(4-chiorobenzyl)pιperazιne; ((2-amιnocarbonylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-amιnocarbonyl-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((4-(2-amιnoethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2,4,6-trι(dιmethylamιno)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-hydroxymethyl-6-methoxyphenoxy)methyl)carDonyl-4-(4-chlorobenzyl)pιperazιne, ((2,3-dιmethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((4-(methoxycarbonyl)-5-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-methoxy-4-(methoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2,6-dιmethoxy-4-(prop-3-enyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-acetyl-5-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-acetyl-4-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-acetyl-3-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-methoxy-4-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2,6-dιmethoxy-4-acetylpheπoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2,6-dι(f-butyt)phenoxy)methyt)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2,4-dι( -butyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((3,5-dι(f-butyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2,6-di(ιsopropyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-methoxy-4-(ethoxycarbony)methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-ethoxy-5-prop-2-enylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-methoxy-5-prop-2-enylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2,6-dι(1-methylpropyl)p enoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2,4-difluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2,6-dιphenylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-nιtro-3-tπfluoromethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ■ ((2-cyclopentypheπoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((4-cyclopentylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; ((2,3-dιfluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-carboxy-6-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; ((2-amιno-4-chloro-5-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((3,4-difluorophenoxy)methy0carbonyl-4-(4-chlorobenzyl)piperazine; ((2-carboxy-6-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,4-dιcarboxyphenoxy)methyl)carDonyl-4-(4-chlorobenzyl)pιperazιne; ((2,3-dιmethoxy-5-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-bromo-4-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyt)pιperazιne; ((2,6-dιchoro-4-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((3-methyl-4-ιsopropylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((fluoren-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; ((2-diethylamιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-amιno-3-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyt)pιperazιne; (((2-0X0-3,4, 8-trιmethyl-2H-1-benzopyran-7-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme; ((2-acetyt-4-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-fluoro-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-(methylcarbonyl)amιno-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((1-acetylnaphthalen-2-yi)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-methoxy-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne; ((3-methyl-5-isopropylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-methyl-4-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((1-amιnonaphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((4-amιnonaphthalen-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-methoxy-4-(1 ,2-dihydroxyethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((3-(2-amιnoethyl)ιndolin-5-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((5-chioroquinolin-8-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-methoxy-4-(2-(amιno)ethyl)phenoxy)methyl)carbonyl-4-(4-chiorobenzyl)pιperazιne, •((4-(2-(amιno)ethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-methoxy-4-(2-(amιno)ethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,4-dιamιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-(dιethylamιno)methyl-4-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methyl-5-(2-amιnobutyi)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-(benzotπazol-2-yl)-4-( 1 ,1 ,3, 3-tetramethylbutyl)phenoxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazine; -((2-nιtro-4-bromo-6-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-ιodophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-(2-carboxyethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-carboxy-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιbromo-3-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιchloro-3-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methoxy-4-carboxyphenoxy)methyl)carbσnyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιmethoxy-4-carboxyphenoxy methyl)carbonyl-4-(4-chlorobeπzyl)pιperazιne, -((4-(2-carboxyethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-(2-hydroxyethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-(2-hydroxyethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-(2-hydroxyethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methoxy-4-(2-hydroxyethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,4-dιbromo-6-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-fluoro-6-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,4-dιchloro-6-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,4-dιιodo-6-formyiphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methoxy-6-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-ethoxy-6-formylphenoxy)methyl)carbonyl-4-(4-chtorobenzyl)pιperazιne, -((2-formyl-5-(dιethylamιno)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-formyl-5-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-formyl-3,5-dιmethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-formyl-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-formyl-4-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ■ (((4-methoxynapthalen-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, •((2-carboxy-5,6-dιmethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((3-nιtro-4-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((fluoren-9-on-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ■ (((4-hydroxy-1 ,2,3,4-tetrahydronaphthalen-8-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme; ((2,3,4,5,6-pentabromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-methyl-3,4,5,6-tetrabromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2,3,4-tπchlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-methyl-4-bromo-6-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, ((2-chloro-4-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2,4,6-tπιodophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-formyl-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((3-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((1-bromoπaphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((1 ,6-dιbromonapthalen-2-y0oxy)methyl)carbonyl-4-(4-chiorobenzyl)pιperazιne, (((1-nιtrosonaphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((2,4-dιchloronaphthalen-1-yi)oxy)methyl)carboπyl-4-(4-chlorobenzyi)pιperazιne, (((2-nιtronaphthalen-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((2-carboxynaphthalen-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((2-methylnaphthalen-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((3-(hydroxysuifonyl)-7-(dιmethylamιno)naphthalen-1-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazine; (((4-methoxynaphthalen-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((1-formylnapthalen-2-yl)oxy)methyi)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((1-carboxynaphthalen-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, •(((1-amιno-4-(hydroxysulfonyi)naphthalen-2-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazine; ■((4-(naphthalen-2-yl)amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, •(((3-amιnonaphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ■((2-fluoro-4-(carboxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-chloro-4-(carboxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-methoxy-4-(carboxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((4-hydroxymethylphenxoy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; ((2-(hydroxymethy0-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne; ((2,6-di(hydroxymethyl)-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-methoxy-4-(hydroxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((4-mercaptophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazme; (((2-carboxyιndol-5-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((3-carboxyιndol-5-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyt)piperazιne; (((ιndol-4-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((ιndol-5-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-(benzoxazol-2-yl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((2-methylquinolin-8-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((5,7-dιbromoquinolin-8-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((5,7-diιodoquinolin-8-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((5-nitroquιnolin-8-yi)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazine; (((quιnoiιn-5-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazine; (((5-(hydroxysulfonyl)-7-iodoquιnolιn-8-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((2-phenyl-4-oxo-4H-1-benzopyran-7-yl)oxy)methyl)carbonyl-4-(4-chiorobenzyl)pιperazιne. ((2-carboxy-2,5,7,8-tetramethyl-2,3-dihydro-1-benzopyran-6-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazine; (((2-oxo-3-chloro-4-methyl-2H-1-benzopyran-7-yl)oxy)methyl)carbonyl-4-(4- chlorobeπzyOpiperazine; (((2-oxo-3-(dιethylamino)methyl)-4-methyl-2H-1-benzopyran-7-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazine; (((2-oxo-6-methoxy-2/-/-1-benzopyran-7-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (((2-oxo-2/- -1-benzopyran-7-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazine; ((2-methoxy-4-formyi-6-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; ((2-methoxy-4-formyl-6-iodophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; ((2-methoxy-4-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; •((2-ethoxy-4-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-carboxy-4-formyiphenox)methyl)carbonyl-4-(4-chtorobenzyl)piperazine; ((2,4-dichloro-6-nitrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,4-dinitro-6-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,4-dinitro-6-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,4-dinitro-6-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,5-dinitrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-nitro-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-nitro-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,4-dinitrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-nitro-4-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-nitro-4-formyl-6-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-nitro-4-carboxyphenoxy)methyl)carbonyl-4-(4-chiorobenzyl)piperazine; ((2-nitro-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,6-dinitro-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-nitro-4-(carboxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,6-dichlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((3-methoxy-5-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((4-cyanophenoxy)methyl)carbonyl-4-(4-chlorobenzyt)piperazine; ((4-(1-methyl-1-phenylethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((3-(ethylamino)-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; (((2-acetylnaphthalen-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2-(carboxymethy0phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((4-(carboxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; (((benzotriazol-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; (((quinoiin-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((4-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,6-dimethoxy-4-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((3,4-dimethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,4,6-tri(f-butyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((2,6-dimethoxy-4-(methoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((3-trifluoromethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyi)piperazine; (2-methyl-5-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (4-(4-cyanophenyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (3-nιtro-4-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (3-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (4-methylphenox)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (4-(methoxycarbonyl)methylphenoxy)methyi)carbonyl-4-(4-chiorobenzyl)pιperazιne, (carbazol-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2-0X0-1 , 3-benzothιol-2-on-6-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-phenyl-4-oxo-4/-/-1-benzopyran-3-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne ( (2-oxo-4-methyl-2H-1-benzopyran-7-yl)oxy)methyl)carbonyl-4-(4-chiorobenzyi)pιperazιne (4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (3-carboxy-4-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2-methoxy-5-amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-phenyl-4-oxo-2,3-dιhydro-4H-1-benzopyran-6-yl)oxy)methyl)carbonyl-4-(4- chlorobenzyOpiperaz e, ((quιnolιn-6-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2,3-dιamιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (4-(hydroxysulfonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((fluorenon-9-on-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((5,6,7,8-tetrahydronaphthalen-1-yl)oxy)methyl)caroonyl-4-(4-chiorobeπzyl)pιperazιne, ((5,6,7,8-tetrahydronaphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2,4,6-tπbromophenoxy)methyl)carbonyl-4-(4-chiorobenzyl)pιperazιne, (2,6-dιbromo-4-cyanophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2,3,5,6-tetrafluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2,6-dιfluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2,3-dιchlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2,3,6-trιchlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2-chloro-4,5-dιmethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2,5-dιchtorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, (2-chloro-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-(methylcarbonyl)amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-ιsopropoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; -((2-(benzyloxy)phenoxy)methyl)carbonyl-4-(4-chiorobenzyl)pιperazιne; -((2-ethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-phenylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-(methoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-(ethoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-(ethylcarbonyl)phenoxy)methyl)carbonyl-4-(4-chiorobenzyl)pιperazιne; -((2-(f-butyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne; -((2-ιsopropylphenoxy)methyl)carbonyl-4-(4-chlorobeπzyl)pιperazιne; -((2-(1-methylpropyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,3-dιmethylphenoxy)methyl)carbonyl-4-(4-chtorobenzyl)pιperazιne; -((2,3,5-tπmethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazine; -((2,3,6-tπmethylphenxoy)methyi)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2,4-dιmethylphenoxy)methyl)carbonyl-4-(4-chtorobenzyl)pιperazιne; -((2,4,6-tπmethoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methyl-5-ιsopropylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,5-dιmethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2,5-dιmethyl-4-(dιethyiamιno)methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-(f-butyl)-6-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,6-dιmethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-prop-3-enyl-6-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-prop-2-enylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((2-ethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne; -((2-n-propylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((3-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3,5-difluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((3-chloro-4-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((3,5-dιchlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; -((3-iodophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ■ ((3-(phenylamino)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ■ ((3-(diethylamino)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ■ ((3-phenylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ■ ((3-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ■ ((3-trifluoromethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ■ ((3-f-butylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ■ ((3-isopropylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ■ ((3-methyl-4-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ■ ((3,4-dimethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; • ((2-f-butyl-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-isopropyl-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-ethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,6-dimethyl-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,6-dibromo-4-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzy0piperazine; •((2-bromo-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-methyl-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzy piperazine; -((2-isopropyl-4-chloro-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(methylcarbonyl)aminophenoxy)methyl)carbonyl-4-(4-chlorobenzy0piperazine; -((4-ethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-propoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-n-butoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzy0piperazine; -((4-t?-hexoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyθpiperazine; -((4-n-heptoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(propoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(ethylcarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(1 ,1 ,3,3-tetramethylbutyl)phenoxy)methy0carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(1 , 1 -dimethylpropyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(1-methylpropyl)p enoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-methoxy-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-acetyl-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-(f-butyl)-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-(ethylamino)-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(methoxycarbonyl)methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-ethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-n-propylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxy-4,6-dibromophenoxy)methyl)carbonyl-4-(4-chlorobenzy piperazine; -((2-carboxy-4,6-dichlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxy-4,6-diiodophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxy-6-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxy-6-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxy-5-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxy-5-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxy-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ■ ((2-carboxy-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxy-4-fluorophenoxy)methy!)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxy-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxy-4-iodophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-carboxy-4-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,3,4-trichlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,3,4,5,6-pentachlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,4 > 5-trichlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-(methoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-(ethoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,6-dimethyl-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3,5-dimethyl-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-methyl-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-isopropyl-4-chloro-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-ethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-(f-buty0-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzy0piperazine; -((3-formyl-4-nitrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-methoxy-4-prop-3-enylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-(1-phenyethy0-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(ethoxycarbonyl)methylphenoxy)methy0carbonyl-4-(4-chlorobenzyl)piperazine; -((4-trifiuoromethoxyphenoxy)methy0carbonyl-4-(4-chlorobenzyl)piperazine; -((3-fluoro-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-fluoro-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -(((7-methoxynaphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-benzyloxy-4-cyanophenoxy)methyl)carbonyl-4-(4-chiorobenzyl)piperazine; -((2-chloro-3,5-dimethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-bromo-3,5-dimethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3,5-dimethoxy-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,6-dibromo-3,5-dimethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzy0piperazine; -((4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-nitrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-methyl-3-nitrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3,5-dimethoxyphenoxy)methy0carbonyl-4-(4-chlorobenzyl)piperazine; -((2-nitro-3-carboxy-6-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-cyanophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-methoxy-5-nitrophenoxy)methyl)carbonyl-4-(4-chlorobenzyθpiperazine; -((2-nitro-5-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-(carboxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-methoxy-5-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(dimethylamino)methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(2-(dimethylamino)ethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -(((naphthalen-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -(((5-aminonaphthalen-1-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-nitro-4-aminophenoxy)methyl)carbonyl-4-(4-chlorobenzyI)piperazine; -((2,6-di(f-butyl)-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzy piperazine; -((3-carboxy-4-nitrophenoxy)methy0carbonyl-4-(4-chlorobenzyl)piperazine; -((2-methyl-5-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-nitro-4-aminophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(benzyloxy)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((4-(aminocarbonyθphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3,5-di(trifluoromethy0phenoxy)methyl)carbonyl-4-(4-chlorobenzy0piperazine; -((2,4-dibromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,6-dibromo-4-methylphenoxy)methy0carbonyl-4-(4-chlorobenzyl)piperazine; -((2,4-dichlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3,5-dimethyl-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyθpiperazine; -((3,5-dicarboxyphenoxy)methyl)carbonyl-4-(4-chlorobeπzyl)piperazine; -((2-chloro-4-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,6-dichloro-4-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -(((2-carboxyquinolin-4-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,6-dimethyl-4-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,6-di(f-butyl)-4-carboxyphenoxy)methy0carbonyl-4-(4-chlorobenzyl)piperazine; -((2-amino-5-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2,6-di(f-buty0-4-(hydroxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzy0piperazine; -(((4-carboxyquinolin-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-nitro-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-ethyl-4-chloro-5-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3,5-di(methoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-(morpholin-4-yl)methyl-4-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-methoxy-4-cyanophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-chloro-4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-trifluoromethylphenoxy)methyl)carbonyl-4-(4-chlorobenzy0piperazine; -((2-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((2-methyl-4-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-(dimethylamino)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; -((3-methyl-4-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((3,5-dιmethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazine; ((4-phenylphenoxy)methyi)carbonyi-4-(4-chlorobenzyl)pιperazιne; ((4-(ethoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((4-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne; ((4-benzylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-methoxy-4-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; (((3-carboxynaphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-(hydroxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((quιnolιn-8-yl)oxy)methyl)carbonyl-4-(4-chtorobenzyl)pιperazιne; ((3-amιnophenoxy)methyl)carDonyl-4-(4-chlorobenzyl)pιperazιne; ((4-(amιnocarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((3,5-dιmethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-(cyclohexyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((quιnolιn-6-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2,4-dιchloro-3-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2,5-dιmethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((3-bromophenoxy)methyl)carbonyl-4-(4-chlorobeπzyl)pιperazιne; ((3-(methylcarbonyl)amιnophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((3-acetylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((3-trιfluoromethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((4-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, ((2-formylphenoxy)methyi)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-methoxy-5-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; (((tropιnon-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-nιtro-5-fluorophenoxy)methyl)carbonyl-4-(4-chtorobenzyl)pιperazιne, ((2-nιtro-5-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((3-formyl-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; ((2-carboxy-5-nitrophenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne; ((2-amιno-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazine; ((2-amιno-3-carboxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)piperazιne; ((2-nιtro-4-amιnophenoxy)methyl)carbonyl-4-(4-chtorobenzyl)pιperazine; -((2,6-dιchloro-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-fluoro-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2,3-dιfluoro-6-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-chloro-4-nιtrophenoxy)methyl)carbonyi-4-(4-chlorobenzyl)pιperazιne > -((2-nιtro-4-cyanophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-bromo-4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3,4-dιchlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3,5-dιchlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3,4,5-trιmethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-fluorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3,5-dιmethyl-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-methoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-(methoxycarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-tπfluoromethylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-f-butylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((4-ιsopropylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((naphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((6-bromonaphthalen-2-yl)oxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-(hydroxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methoxy-5-(hydroxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -(((1 ,3-benzodιoxolan-5-yl)oxy)methyl)carbonyl-4-(4-chiorobenzyl)pιperazιne, -((2,6-dιmethyl-4-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-methoxy-4-(amιno)methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-(amιnocarbonyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((3-(methoxycarbonyl)methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, -((2-(4-phenyicarbonyl)-4-fluorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, -((2-(1 -methyl)cyclohexyl-2,4-dιmethylphenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, -((2-(benzyloxycarbonyl)phenoxy)methyl)carbonyi-4-(4-fluorobenzyl)piperazine; -((2-(4-(methyl)phenylcarbonyl)-5-methoxyphenoxy)methyl)carbonyl-4-(4- fluorobenzyOpiperazine; -((2-phenylcarbonyl-5-octoxyphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)piperazine; -((4-octylphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)piperazine; -((2-(2-(carboxy)phenylcarbonyl-5-di(n-butyl)aminophenoxy)methyl)carbonyl-4-(4- fluorobenzyOpiperazine; -((2-phenylcarbonyl-5-methoxyphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)piperazιne; -((2-methoxy-4-(3-hydroxyprop-2-enyl)phenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; -(((3-(phenylamιπocarbonyl)naphthalen-2-yl)oxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; -(((6-(phenylcarbonyl)naphthalen-2-yl)oxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; -((2-((2-phenytethyl)carbonyl)phenoxy)methyl)carbonyl-4-(4-fluorobenzyi)piperazιne; -((4-((4-fluorophenyl)carbonyl)phenoxy)methyl)carbonyl-4-(4-fluorobenzyl)piperazιne; -((2-(phenyiamino)carbonylphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; -((2-phenylcarbonyiphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; -((2-phenylcarbonyl-4-chloro-5-methylphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; -((4-(4-chlorophenyl)carbonylphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; -((4-benzylcarbonyl)pheπoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; -((2-pheπylcarbonyl-4-methylphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazine; -((4-(2-methylcarbonylethyl)phenoxy)methyi)carbonyl-4-(4-fluorobenzyl)pιperazιne; -((4-phenylcarbonylphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; and -((3-phenylcarbonylphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; D. In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 3 Compounds of Formula (la) and Formula (lb) A. To a solution of 1-((3,4,5-trιmethoxyphenoxy)methyl)carbonylpiperazιne (0.22 g, 0.70 mmol) in 1 % acetic acid in methanol (6 mL) was added 4-cyanobenzaldehyde (0.33 g, 2.5 mmol) and sodium cyanoborohydride (0.093 g, 1.4 mmol). The resultant mixture was stirred at ambient temperature for 1.5 hours and the mixture was then concentrated of volatiies in vacuo. Residue was taken up in ethyl acetate and washed with saturated aqueous NaHC0 3 solution, water, and then brine. The organic layer was separated, dried over MgS0 , filtered and concentrated in vacuo to afford a yellow oil. Purification by flash column chromatography on silica gel afforded 0.21 g of 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(4- cyanobenzyOpiperazine, a compound of formula (lb), as a clear oil: NMR (CDCI 3 ) 7 6 (d, 2), 7 4 (d, 2), 6.2 (s, 2), 4.6 (s, 2), 3.8 (s, 6), 3.75 (s, 3), 3.6 (m, 4), 3.5 (s, 2), 2.2 (m, 4) ppm. B. In a similar manner, other compounds of formula (lb) were made: 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(3,4-dιmethoxybenzyl)pιperazιne; 1-((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(4-methoxybenzyl)pιperazιne; 1 -((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(3-chlorobenzyl)pιperazιne, 1-((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(3-trιfluoromethylbenzyl)pιperazιne, 1-((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(2,3-dιmethyl-4-methoxybenzyl)pιperazιne, 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(3-phenoxybenzyl)pιperazine; 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(4-(dιmethylamιno)benzyl)pιperazιne, 1 -((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(4-(methylthιo)benzyl)pιperazιne; 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(4-methoxy3-methylbenzyi)pιperazιne; 1-((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(2-chlorobenzyl)pιperazιne; 1-((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(3-nιtrobenzyl)pιperazιne; 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(4-hydroxybenzyl)pιperazιne; 1-((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(3,5-dιbromo-4-hydroxybenzyl)pιperazιne, 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(2-fluorobenzyl)pιperazιne; 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7 3 (m, 2), 7. 0 (m, 2), 6.2 (s, 2), 4.6 (s, 2), 3.9 (m, 9), 3.6 (m, 4), 3.4 (s, 2), 2.4 (m, 4) ppm, 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(4-bromobenzyl)pιperazιne; NMR (CDCI 3 ) 7 4 (d, 2), 7.2 (d, 2), 6.2 (s, 2), 4.6 (s, 2), 3.85 (s, 6), 3.75 (s, 3), 3.6 (m, 4), 3.4 (s, 2), 2 4 (m, 4) ppm; 1 -((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(2-bromobenzyl)pιperazine; 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(3-fluorobenzyl)pιperazιne; 1-((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(3-bromobenzyl)pιperazιne; 1-((3,4,5-trimethoxyphenoxy)methyl)carbonyl-4-(3-cyanobenzyl)pιperazιne; 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(2,4-difluorobenzyl)piperazine; 1-((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(2,3-dιfluorobenzyl)pιperazιne, 1 -((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(3,4-dιfluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7.3-7.0 (m, 3), 6.2 (s, 2), 4.6 (s, 2), 3.85 (s, 6), 3.75 (s, 3), 3.6 (m, 4), 3 5 (s, 2), 2 4 (m, 4) ppm; 1 -((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(2,6-dιfluorobenzyl)pιperazιne; 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, NMR (CDCI 3 ) 7 2 (m, 4), 6 2 (s, 2), 4.6 (s, 2), 3 85 (s, 6), 3 75 (s, 3), 3.6 (m, 4), 3.5 (s, 2), 2 4 (m, 4) ppm, 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(3-chioro-4-fluorobenzyl)pιperazιne, 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(4-tπfluoromethylbenzyl)pιperazιne, 1 -((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(4-nιtrobenzyl)pιperazιne, 1 -((3,4,5-trιmethoxyphenoxy)methyt)carbonyl-4-(4-fluorobeπzyl)pιperazιne, 1 -((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(2,5-dιfluorobenzyi)pιperazιne, 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(3-nιtro-4-hydroxybenzyi)pιperazιne, 1 -((4-chlorophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7 2 (m, 4), 7.0 (t, 2), 6.8 (d, 2). 4 6 (s, 2), 3 6 (m, 4), 3 4 (s, 2), 2 4 (m, 4) ppm, 1 -((4-chtorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, NMR (CDCI 3 ) 7.2 (m, 6), 6 8 (d, 2), 4 6 (s, 2), 3 6 ( , 4), 3 5 (s, 2), 2 4 (m, 4) ppm, 1 -((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(3-(benzyloxy)benzyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-4-(3,4,5-tπmethoxybenzyl)pιperazιne, C In a similar manner, the following compounds of formula (la) were made (3S)-1-((4-chlorophenoxy)methyl)carbonyl-3-methyl-4-(4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 7 3 (m, 4), 7.0 (t, 2), 6 9 (d, 2), 4 6 (s, 2), 4 0 (m, 2), 3 7 (m, 1 ), 3 4-2 9 (m, 3), 2 7 (m, 1 ), 2.5 (m, 1 ), 2 1 (m, 1 ), 1 1 (m, 3) ppm, (3R)-1-((4-chlorophenoxy)methyl)carbonyi-3-methyl-4-(4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4 6 (s, 2), 4 0 (m, 2), 3.7 ( , 1 ), 3 4-2 9 (m, 3), 3.2 (m, 1 ), 3.0 (m, 1 ), 2.7 (m, 1 ), 2.5 (m, 1 ), 2.1 (m, 1 ), 1 1 (m, 3) ppm, 1-((4-chlorophenoxy)methyl)carbonyl-3-(2-((((4-chlorophenoxy)methyl)carbonyl)oxy)ethyl)-4-(4- fluorobenzyOpiperazine; 1-((4-chlorophenoxy)methyl)carbonyl-2-hydroxyethyl-4-(4-fluorobenzyl)pιperazιne, dihydrochloride salt; 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-((2-methylpropyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.1 (m, 4), 6.9 (t, 2), 6.7 (d, 2), 4.6 (s, 2), 4 4 (d, 1 ), 3.6 (d, 1 ), 3.3 (m, 3), 2.7-2.3 (m, 6), 2.0-1.7 (m, 5), 0.8 (t, 6) ppm; 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-((4-fluorobenzyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazine, hydrochloride salt; 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-((2-hydroxyethyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazine; 1 -((4-chlorophenoxy)methyl)carbonyl-2-(2-((methyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazme; 1-((4-chlorophenoxy)methyl)carbonyl-3-(2-((4-fluorobenzyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazine, hydrochloride salt; 1-((4-chlorophenoxy)methyl)carbonyl-3-(2-((methyl)amιno)ethyl)-4-(4- fluorobenzyl)piperazine; 1-((4-chlorophenoxy)methyl)carbonyl-3-(2-((2-hydroxyethyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazine; 1 -((4-chlorophenoxy)methyl)carbonyl-3-(2-((2-methylpropyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazme; (fraπs)-1-((4-chloro-2-(((ethyl)amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7 3 (m, 4), 7.0 (d, 2), 6.9 (t, 1 ), 6 4 (br s, 2). 5 0- 4.6 (m, 3), 4.0 (m, 3), 3.7-3.2 (m, 4), 3.0-2 7 (m, 3), 2.2 (m, 1 ), 1.3 (m, 6), 1.0 (br d. 3) ppm; (frans)-1-((4-chloro-2-(((diethyl)amino)methyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.5 (d, 1 ), 7.3 (m, 2), 7.2 (dd, 1 ), 7.0 (t, 2), 6.8 (d, 1 ), 4.7 (m, 3), 4.2 (m, 1 ), 3.6-3.4 (m, 4), 3.2 (m, 1 ), 3.0 (m, 1 ), 2.7 (dd, 1 ), 2.6 (q, 2), 2.2 (d, 1 ), 1.3 (m, 3), 1.0 (m, 9) ppm; (frat7s)-1-((4-chioro-2-(((cyclopropyl)amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (d, 2), 6.8 (t, 1 ), 4.8-4.0 (m, 6), 3.7-3.2 (m, 3), 3.0 (br s, 1 ), 2.7 (d, 1 ), 2.2 (m, 2), 1.3 (m, 3), 0.9 (m, 3), 0.5 (m, 4) ppm, (frans)-1-((4-chioro-2-(((dιmethyl)amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 4), 7.1 (dd, 1 ), 7.0 (t, 2), 6.8 (d, 1 ), 4.7 (m, 3), 4.1 (m, 1 ), 3.6-3.4 (m, 4), 3.0 (br s, 1 ), 2.7 (dd, 1 ), 2.2 (m, 8), 1.3 (m, 3), 0 9 (m, 3) ppm; (frans)-1-((4-chloro-2-(((methyl)amino)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMP (CDCI 3 ) 7.3 (m, 4), 7.1 (dd, 1 ), 7.0 (t, 2), 6.8 (d, 1 ), 4.7 (m, 2), 4.1 (m, 1 ), 3.7-3.4 (m, 5), 3.0 (br s, 1 ), 2.7 (dd, 1 ), 2.4 (s, 3), 2.2 (m, 2), 1.3 (m, 3), 0.9 (m, 3) ppm; (fraπs)-1-((4-chloro-2-((amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 4), 7.1 (dd, 1 ), 7.0 (t, 2), 6.7 (d, 1 ), 4 7 (m, 2), 3.8 (d, 1 ), 3.5 (m, 4), 3.0 (br s, 1 ), 2.7 (dt, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-((4-methylpιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyi)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.1 (dd, 1 ), 7.0 (t, 2), 6.8 (d, 1 ), 4 7 (m, 4), 4.2 (m, 1 ), 3.8 (m, 1 ), 3.6-3.0 (m, 8), 2.9 (t, 1 ), 2.7 (m, 1 ), 2.5-2.2 (m, 6), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-((pιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (DMS0-d 6 ) 7.9 (m, 3), 7.7 (s, 2), 7.4 (t, 1 ), 7.2 (m, 2), 5.4 (d, 1), 5.0 (m, 2), 4.3 (m, 4), 3.6-3.1 (m, 12), 2.8 (m, 1 ), 1.5-1.0 (m, 6) ppm; (frans)-1-((4-chtoro-2-(((2-hydroxyethyl)amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)piperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7 1 (dd, 1 ), 7.0 (t, 2), 6.7 (d, 1 ), 4 7 (m, 2), 4.2-3.4 (m, 6), 3.0 (br s, 2), 2.7 (m, 4), 2.2 (d, 2), 1.3 (m, 3), 0.9 (m, 3) ppm, (frans)-1-((4-chloro-2-((morpholin-4-yt)methyl)phenoxy)methyi)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 3), 7 1 (dd, 1 ), 7.0 (t, 2), 6 7 (d, 1 ), 4 7 (m, 2), 4.1-3.4 (m, 1 1 ), 3.0 (br s, 1 ), 2.7 (dd, 1 ), 2.5 (t, 4), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (fraπs)-1-((4-chloro-2-(ethylamιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 3), 7.2 (dd, 1 ), 7.0 (t, 2), 6.8 (m, 1 ), 4 7 (m, 2), 4.1 (m, 1 ), 3.8 (s, 2), 3.6 (m, 1 ), 3.5 (q, 2), 3.0 (m, 1 ), 2.7 (m, 3), 2.6 (q, 2), 1.3 (m, 3), 1.1 (t, 3), 1.0 (m, 6) ppm; (frans)-1-((4-chloro-2-((ethyl)(1-methylbutyl)amιnomethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)piperazιne; NMR (DMS0-d 6 ) 7.9 (m, 1 ), 7.7 (m, 2), 7.5 (m, 1 ), 7.2 (m, 3), 5.1 (m, 1 ), 4.6 (d, 1 ), 4.3 (m, 2), 3.7-2.8 (m, 6), 2.5 (s, 2), 1.5-1.2 (m, 19), 0.8 (s, 3) ppm; (frans)-1-((4-chloro-2-(benzylamιno)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 7), 7.0 (t, 2), 6.7 (d, 1 ), 6.6 (m, 2), 4.7 (d, 2), 4.4 (s, 2), 4.2-3.0 (m, 8), 2.6 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-((1-methylbutyl)amino)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; NMR (DMSO-d 6 ) 7.9 (m, 2), 7.3 (t, 2), 7.1 (m, 1 ), 6.9 (d, 2), 5.2 (d, 1 ), 4.9 (m, 2), 4.6 (m, 1 ), 4.5-3.2 (m, 6), 2.8 (t, 1 ), 2.5 (s, 1 ), 1.7-1.2 (m, 9), 0.9 (d, 6) ppm; (frans)-1-((4-chloro-2-((cyclopropylmethyl)amιnomethyl)phenoxy)methyl)carbonyl-2,5-dimethyl- 4-(4-fluorobenzyl)piperazιne; NMR (CDCI 3 ) 7.3 (m, 3), 7.1 (dd, 1 ), 7.0 (t, 2), 6.8 (br d, 1 ), 4.7 (m, 2), 3.8 (s, 2), 3.6 (m, 1 ), 3.5 (q, 2), 3.0 (m, 2), 2.7 (dd, 1 ), 2.4 (m, 3), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 4), 0.4 (m, 2), 0.1 (m, 2) ppm; (frans)-1-((4-chloro-2-(phenylamιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (DMSO-d 6 ) 7.8 (m, 2), 7.4 (m, 8), 7.2 (m, 2), 5.4 (d, 1 ), 5.0 (m, 2), 4.7 (m, 1 ), 4.5 (s, 2), 4.3 (m, 2), 3.9-3.4 (m, 4), 1.4 (m, 3), 1.2 (m, 3) ppm; (fraπs)-1-((4-chloro-2-(1-((methyl)(ethyl)amιno)ethyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4- (4-fluorobenzyl)piperazιne; NMR (CDCI 3 ) 7.4 (s, 1 ), 7.3 (m, 2), 7.1 (dd, 1 ), 7.0 (t, 2), 6.8 (br d, 1 ), 4.6 (br s, 3), 4.0 (m, 2), 3.6 (d, 1 ), 3.4 (d, 1 ), 3.0 (m, 1 ), 2.7 (dd, 1 ), 2.5 (d q, 1 ), 2.4 (d q, 1 ), 2.2 (s, 3), 1.3 (m, 6), 1.0 (m, 6) ppm; (frans)-1-((4-chloro-2-(1-(dιmethylamιno)ethyl)phenoxy)methyi)carbonyi-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CD 3 OD) 7.6 (m, 3), 7.5 (d, 1 ), 7.3 (m, 3), 5.1 (m, 3), 4 4 (m, 2), 3.8 (dd, 2), 3.6 (m, 1 ), 3.4 (m, 1 ), 3.0 (m, 1 ), 2.6 (m, 7), 1.6 (m, 6), 1.3 (m, 3) ppm; (2R)-1-((4-chloro-2-((4-f-butoxycarbonylpιperazιn-1-yl)methyt)phenoxy)methyl)carbonyl-2- methyl-4-(4-fluorobenzyl)piperazιne; NMR (CDCI 3 ) 7.3 (m, 3), 7.0 (t, 2), 6.8 (d, 1 ), 4.7 (m, 2), 4.4 (m, 1 ), 3.5 (m, 10), 3.0 (m, 1 ), 2.8 (m, 1 ), 2.6 (m, 2), 1.4 (m, 12), 1.2 (m, 3) ppm; (frans)-1-((4-chloro-2-((4-f-butoxycarbonylpιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2,5- dimethyl-4-(4-fluorobenzyl)piperazιne; NMR (DMSO-d 6 ) 7.8 (m, 2), 7.6 (s, 1 ), 7.5 (m, 1 ), 7.3 (t, 2), 7.2 (m, 1 ), 5.4 (d, 1 ), 5.0 (m, 2), 4.7 (m, 1 ), 4.3 (m, 6), 4.0 (m, 2), 3.8-3.1 (m, 8), 2.9 (m, 1 ), 1.4 (m, 12), 1.2 (m, 3) ppm; 1-((4-chloro-2-(morpholin-4-ylmethyl)phenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperaz e; NMP (DMSO-d 6 ) 1 1.5 (br d, 1 ), 10.6 (m, 1 ), 7.7 (m, 2), 7.6 (s, 1 ), 7.5 (dd, 1 ), 7.3 (t, 2), 7.2 (d, 1 ), 5.2 (q d, 2), 4.7 (m, 1 ), 4.4 (m, 4), 3.9-3.7 (m, 4), 3.5 (m, 1 ), 3.4 (m, 4), 3.0 (m, 4), 2.8 (m, 1 ), 1.5 (d, 1.5), 1.3 (d, 1.5) ppm; and D. In a similar manner, the following compound of formula (Id) was prepared: 1-((4-chtorophenoxy)methyl)carbonyl-2-methyl-4-(2-bromothienyl)methylpιperazιne; NMR (CDCI 3 ) 7.2 (d, 2), 6.8 (dd, 3), 6.6 (d, 1 ), 4.6 (s, 2), 3.6 (s, 4), 3.5 (t, 2), 2.4 (q, 4) ppm. E. In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 4 Compounds of Formula (la) A. To a solution of (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyl)-5-((hydroxy)methyl)piperazιne (0.17 g, 0.42 mmol) in CH 2 CI 2 (50 mL) at 0°C was added tπethylamine (excess) and methane sulfonyl chloride (0.050 mL, 0.5 mmol). The resultant mixture was stirred at 0°C until consumption of alcohol was observed by TLC analysis The mixture was concentrated of volatiles in vacuo. Residue was taken up in anhydrous DMF (5 mL) and K 2 C0 3 (excess) added, followed by tetrazole (0.050 g, 0.71 mmol). The resulting mixture was stirred at ambient temperature for 3 days and filtered. The filtrate was concentrated in vacuo and the residue taken up in ethyl acetate. This was washed with water then brine, then dried over MgS0 4 and concentrated in vacuo to afford a yellow oil. Purification by flash column chromatography on silica gel afforded 25 mg of (2R,5R)-1-((4- chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((tetrazolyl)methyl)pιperazιne as a white solid: NMR (CDCI 3 ) 7.3 (m, 5), 7.0 (m, 4), 4.8-4.1 (m, 5), 3.8 (m, 3), 3.2 (m, 2), 2.8 (dd, 1 ), 2.5 (dd, 1 ), 1.4 (d, 3) ppm, MS (ESI) 458. B. In a similar manner, the following compounds of formula (la) were made: (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((1 ,2,4-trιazol-2- yl)methyl)piperazιne; NMR (CDCI 3 ) 7.9 (s, 1 ), 7.3(m, 5), 6.9 (m, 4), 4.7 (m, 3), 4.4-3.4 (m, 5), 3.1-2.7 (m, 2), 2.4 (t, 1 ), 2.0 (d, 1 ), 1.2 (m, 3) ppm; (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((morpholιn-4- yl)methyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 4.7-4.1 (m, 5), 3 9- 3.4 (m, 9), 3.2-2.7 (m, 3), 2.3 (m, 2), 2.0 (m, 1 ), 1.2 (m, 3) ppm; (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((pιperazιn-1 - yl)methyl)pιperazιne; (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-((diethylamιno)methyt)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4 7 (m, 3), 3.9-3.4 (m, 4), 2.8-2.3 (m, 7), 1.2 (m, 3), 0.9 (t, 6) ppm; (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-(((ethyl)amιno)methyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4 7 (m, 3), 4.2-3 4 (m, 5), 2.8-2.3 (m, 6), 1.3-1 0 (m, 6) ppm; (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((4-methyl- pιperazιn-1-yl)methyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4 7 (m, 3), 3.9-3 4 (m, 4), 2.8-2.2 (m, 14), 1.2 (m, 3) ppm; 1-((4-chlorophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)-3-(2-(4-(f-butoxycarbonyl)- pιperazιn-1-yl)ethyl)pιperazιne, hydrochloride salt (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-((dιmethylamιno)methyl)pιperazιne (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-(((cyclopropyl)amιno)methyi)pιperazιne (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluoroDenzyl)- 5-((cyano)methyl)pιperazιne; NMR (CDCI 3 ) 7 3 (m, 4), 7.0 (m, 4), 4.6 (m, 4), 4 2-3 2 (m, 4), 2.6-2.2 (m, 4), 1.2 (m, 3) ppm; (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-((((cyclopropyl)methyl)amιno)methyl)pιperazιne; (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluoroDenzyl)- 5-(((2-hydroxyethyl)thιo)methyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 4.7 (m, 3), 4.1-3.5 (m, 5), 3.1-2.3 (m, 8), 1.3 (m, 3) ppm; (frans)-1-((4-chloro-2-(imιdazot-1-ylmethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (DMSO-d 6 ) 11.3 (m, 1 ), 9.4 (s, 1 ), 7.9 (s, 3), 7.6 (s, 2), 7 4 (m, 1 ), 7.3 (m, 3), 7.1 (m, 1 ), 5.4 (m, 2), 4.9 (m, 1 ), 4.2 (m, 2), 3.8-3.2 (m, 6), 2 7 (m, 1 ), 1 4-1.2 (m, 6) ppm; (fraπs)-1-((4-chloro-2-(1-(imidazol-1-yl)ethyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.6 (s, 1 ), 7.3 (m, 2), 7.2 (dd, 1 ), 7.0 (m, 5), 6.8 (d, 1 ), 5.8 (q, 1 ), 4.6 (m, 3), 4.2 (m, 1 ), 3.5 (q, 2), 3.2 (m, 1 ), 3.0 (m, 1 ), 2.7 (dd, 1 ), 2.2 (dd, 1 ), 2.0 (br s, 1 ), 1.8 (dd, 3), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1 -((4-chloro-2-(triazol-1 -ylmethyl )phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 8.4 (s, 1 ), 7.9 (s, 1 ), 7.3 (m, 3), 7.0 (t, 2), 6.8 (d, 1 ), 5.4 (s, 2), 4.6 (m, 3), 4.2 (m, 1 ), 3.5 (q, 2), 3.2 (m, 1 ), 3.0 (m, 1 ), 2.9 (dd, 1 ), 2.2 (dd, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; and (frans)-1-((4-chloro-2-(tetrazol-1-ylmethyl)phenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 9.4 (s, 1 ), 7.4 (s, 1 ), 7.3 (m, 3), 7.0 (t, 2), 6.8 (d, 1 ), 5.6 (s, 2), 4.7 (m, 3), 4.2 (m, 1 ), 3.5 (q, 2), 3.2 (m, 1 ), 3.0 (m, 1 ), 2.9 (dd, 1 ), 2.2 (dd, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm. C. In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 5 Compounds of Formula (la) A. To a solution of oxalyl chloride (0.62 g, 5 mmol) in CH 2 CI 2 (20 mL) at -50°C was added DMSO (0.85 g, 1 1 mmol, in solution of 5 mL of CH 2 CI 2 ) over 2 minutes. 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)caroonyl-3-(2-hydroxyethyl)piperazine (1 85 g, 4.5 mmol, in solution of 5 mL of CH 2 CI 2 ) was added The resulting mixture was stirred at -50°C for 15 minutes, then triethyiamme (2.3 g, 22 mmol) was added. After 5 minutes at -50°C, the mixture was gradually warmed to ambient temperature. At that time the mixture was diluted with CH 2 CI 2 and washed with water, then brine. The organic layer was then dried over MgS0 and concentrated in vacuo to afford 1.7 g of 4-(4-fluorobenzyl)-1-((4- chlorophenoxy)methyl)carbonyl-3-((formyl)methyl)pιperazιne as a yellow oil; NMR (CDCI 3 ) 9.8 (d, 1 ) 7.3 (m, 4), 7.0 (m, 4), 4.6 (m, 3), 3.8-3.2 (m, 7), 2.7-2.2 (m, 4) ppm. B. In a similar manner, the following compounds of formula (la) were made: 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-((acetyl)methyt)pιperazιne, hydrochloride salt; NMR (CDCI 3 ) 7.3 (m, 4), 6.9 (m, 4), 4.6 (m, 2), 3.8-3 3 (m, 7), 2 4 (m, 4), 2.1 (d, 3) ppm; and (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-formylpιperazιne. C In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 6 Compounds of Formula (la) A To a solution of 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3- ((formyθmethyl)pιperazιne (0.31 g, 0 77 mmol) in anhydrous THF (20 mL) was added methyl magnesium bromide (0.26 mL, 0.77 mmol, 3.0 M solution in ether) The resultant mixture was stirred overnight at ambient temperature. At that time the mixture was poured into 5% aqueous NH 4 CI solution and extracted with two portions of ether The combined organic extracts were washed with brine, then dried over MgS0 , filtered and concentrated in vacuo to afford a yellow oil Purification by flash column chromatography on silica gel afforded 0.29 g of 4-(4- fluorobenzyl)-1-((4-chiorophenoxy)methyl)carbonyl-3-(2-hydroxypropyl)pιperazιne, as a clear, colorless oil, which was converted to its hydrochloride salt, NMR (CDCl 3 ) 7 6 (m, 2), 7 2 (m, 4), 6 9 (m, 2), 4.7 (m, 2), 4 4-3.0 (m, 10), 2.4-1 4 (m, 2), 1 3-1 0 (m, 3) ppm B In a similar manner, the following compounds of formula (la) were made 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxy-2-phenylethyl)pιperazιne, NMR (CDCI 3 ) 7.3 (m, 9), 7 0 (t, 2), 6.8 (d, 2), 4 9 (m, 1 ), 4 8 (m, 2), 4 1 (m, 1 ), 3 8-3 3 (m, 6), 2.8 (m, 2), 2.2 (m, 1 ), 2.0 (m, 2) ppm, 4-(4-fluorobenzyl)-1-((4-chiorophenoxy)methyl)carbonyl-3-(2-hydroxypentyl)pιperazιne, NMR (CDCI 3 ) 7.8 (m, 2), 7.3 (m, 4), 6.9 (d, 2), 4.8 (d, 2), 4.5-3.0 (m, 16) 2 2-1.2 (m, 8), 0.9 (m, 3) ppm; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxybut-4-enyl)pιperazιne, NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 5.7 (m, 1 ), 5.2 (dd, 1 ), 5.1 (t, 1 ), 4.6 (m, 2), 4.2-3.3 (m, 7), 2.9 (m, 2), 2.4 (m, 1 ), 1.9-1.5 (m, 2) ppm; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxy-2-(4-methylphenyl)- ethyOpiperazine; (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1-hydroxyprop-2- enyOpiperazme, hydrochloride salt; NMR (DMSO-d 6 ) 10.1 (b s, 1 ), 7.6 (m, 2), 7.3 (d, 4), 6.9 (d, 2), 6.1 (m, 1 ), 5.9 (m, 1 ), 5.4 (m, 2), 4.8 (m, 2), 4.4 (m, 4), 3.7-3.1 (m, 5), 1 1 (m, 3) ppm; (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1- hydroxybutyOpiperazme, hydrochloride salt; NMR (DMSO-d 6 ) 10.3 (b s, 1 ), 7.6 (m, 2), 7.3 (m, 4), 6.9 (d, 2), 5.6 (m, 1 ), 4.9 (m, 2), 4.4 (m, 3), 3.9-3.1 (m, 5), 1.4 (m, 4), 1.1 (d, 3), 0.8 (t, 3) ppm; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxybut-4-ynyl)pιperazιne; 4-(4-fluorobenzyl)-1 -((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxy-2-cyclohexylethyl)- piperazme; (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyi)carbonyl-2-methyl-5-(1- hydroxyethyOpiperazme, hydrochloride salt; NMR (DMSO-d 6 ) 10.3 (b s, 1 ), 7.6 (m, 2), 7.3(m, 4), 6.9 (d, 2), 5.6 (b s, 1 ), 4.9 (m, 2), 4.6-4.0 (m, 6), 3.2 (m, 3), 1.2 (d, 3), 1 1 (d, 3) ppm; (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1- hydroxy-1-(phenyl)methyl)piperazιne, hydrochloride salt; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-5-(2-hydroxy-2-methylpropyl)- piperazme; (fraπs)-1-((4-chloro-2-(1-hydroxyethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 3), 7.2-6.8 (m, 4), 5.1 (m, 1 ), 4.7 (m, 2), 4.2-3.0 (m, 9), 2.7 (dd, 1 ), 2.3 (d, 1 ), 1.5 (d, 3), 1.3 (br m, 3), 0.9 (br m, 3) ppm; 1-((4-chlorophenoxy)methyl)carbonyl-2-(1-hydroxyethyl)-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7.2 (m, 4), 7.0 (m, 2), 6.8 (dd, 2), 4.7 (m, 3), 4.2 (m, 1 ), 3.8 (m, 1 ), 3.4 (s, 2), 3.2 (m, 1 ), 2.3 (dd, 1 ), 2.1 (m, 1 ), 1.1 (m, 3) ppm; 1-((4-chlorophenoxy)methyi)carbonyl-2-(2-hydroxypropyl)-4-(4-fluorobenzyl)piperazιne; NMR (DMSO-d 6 ) 7.6 (br s, 2), 7.3 (d, 4), 6.9 (q, 2), 4.9 (m, 3), 4.3 (m, 3), 3.9 (m, 3), 3.3. (m, 2), 3.0 (m, 1 ), 2.2 (t, 1 ), 1.8 (m, 1 ), 1.5 (m, 1 ), 1.1 (d, 1.5), 1.0 (d, 1.5) ppm; and 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-hydroxybut-3-enyl)-4-(4-fluorobenzyl)piperazιne, NMR (DMSO-d 6 ) 7.6 (dt, 2), 7.3 (m, 4), 6.9 (t, 2), 5.8 (m, 1 ), 5.2 (dd, 1 ), 5.0 (dt, 2), 4.8 (dt, 1 ), 4.4 (m, 2), 3.9 (m, 1 ), 3.4 (m, 3), 3.0 (m, 3), 2.2 (m, 1 ), 1.8 (m, 1 ), 1.6 (m, 1 ) PPm. C. In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 7 Compounds of Formula (la) A. To a solution of 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2- hydroxy-2-phenylethyl)pιperazιne (0.051 g, 0.11 mmol) in anhydrous ether (5 mL) was added sodium hydride (0.006 g, 0.15 mmol). The resultant mixture was stirred at ambient temperature for 30 minutes, then methyl iodide (0.016 g, 0 1 1 mmol) was added. Once thin layer chromatography analysis showed complete consumption of 4-(4-fluorobenzyl)-1-((4- chlorophenoxy)methyl)carbonyl-3-(2-hydroxy-2-phenylethyl)pιperazιne had occurred, the mixture was poured into water and extracted with two portions of ether. The combined organic extracts were dried over MgS0 , filtered and concentrated in vacuo to afford 0.046 g of 4-(4- fluorobenzyl)-1 -((4-chlorophenoxy)methyl)carbonyl-3-(2-methoxy-2-phenylethyl)pιperazιne as a yellow oil: NMR (CDCI 3 ) 7.3 (m, 9), 7.0 (m, 2), 6 9 (m, 2), 4.8 (m, 3), 4.2 (m, 2), 3.9-3.2 ( , 5), 3.1 (d, 2), 3.0 (s, 1 ), 2.9 (s, 1 ), 2.6 (m, 1 ), 2.4 (m, 1 ), 1.9 (m, 1 ) ppm. B. In a similar manner, other compounds of the invention were made' (2R,5R)-4-(4-fluorobenzyl)-1-((4-chiorophenoxy)methyl)carbonyl-2-methyl-5-((methoxy)- methyOpiperazine; NMR (CDCl 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4 6 (m, 3), 3.8-3 1 (m, 9), 3.0 (br s, 1 ), 2.7 (dd, 1 ), 2.3 (t, 1 ), 1.2 (m, 3) ppm; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-(methoxy)ethyl)pιperazιne, NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (d, 2), 4.7 (m, 3), 4.1 (m, 1 ), 3.7 (m, 1 ), 3 4-3.2 (m, 6), 2.8 (m, 3), 2.0 (m, 4) ppm; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(ethoxycarbonyi)methyl- pιperazιne-2-one; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonylpιperazιne-2-one; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-((methoxy)methyl)pιperazιne, NMR (CDCl 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (dd, 2), 4.7 (d, 2), 3.9-3.3 (m, 1 1 ), 2.6 (m, 2), 2.2 (m, 1 ) ppm; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-(methoxy)ethyl)pιperazιne, NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.9 (dd, 2), 4.7 (d, 2), 3.8-3.3 (m, 11 ), 2.6 (m, 2), 2.2 (m, 1 ), 1.8 (m, 2) ppm; 4-(4-fluorobenzyl)-1-(2-(4-chlorophenoxy)ethyl)piperazιn-2-one; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 4.2 (t, 2), 3.8 (t, 2), 3.5 (m, 4), 3.2 (s, 2), 2.6 (t, 2) ppm; 4-(4-fluorobenzyl)-1-(2-(4-chlorophenoxy)ethyl)-3-((ethoxycarbonyl)methyl)pιperazιn-2-one, hydrochloride salt; NMR (CDCI 3 ) 7.2 (m, 2), 7.1 (m, 4), 6.8 (d, 2), 4.2 (m, 9), 3.5 (m, 5), 2.9 (br s, 1 ), 1.3 (t, 3) ppm; (fraπs)-1-((4-chloro-2-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 2), 7.0-6.8 (m, 5), 4 7 (br m, 2.5), 4.2 (br s, 0.5), 3.8 (s, 3), 3.6-3.2 (m, 4), 3.0 (br s, 1 ), 2.7 (m, 1 ), 2.2 (d, 1 ), 1.2 (br m, 3), 1 9 (br m , 3) ppm; and (frans)-1-((5-chloro-2-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 2), 7.0-6.8 (m, 5), 4 7 (br m, 2.5), 4.2 (br s, 0.5), 3.8 (s, 3), 3.6-3.2 (m, 4), 3.0 (br s, 1 ), 2.7 (m, 1 ), 2.2 (d, 1 ), 1.2 (br m, 3), 1 9 (br m , 3) ppm. C In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 8 Compounds of formula (la) A. To a solution of 4-chlorobenzylιsocyanate (0.59 g, 3.5 mmol) in anhydrous THF (15 mL) at 0°C was added 1-(4-chlorobenzyl)pιperazιne (0.74 g, 3.5 mmol). The resultant mixture was stirred at ambient temperature. After 20 hours the mixture was concentrated of volatiles. The resulting solid was washed with ethyl acetate and dried in vacuo to afford 0 72 g of 1-(((4-chlorobenzyl)amιno)carbonyl)-4-(4-chlorobenzyl)pιperazιne as a white solid; NMR (CDCI 3 ) 7.4 (m, 4), 7.3 (m, 2), 7.2 (m, 2), 4 4-4.1 (m, 6), 3.6 (m, 4), 3.0 (m, 2) ppm B. In a similar manner, other compounds of formula (la) were made: 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(Λ/-methylureido)- amιno)methyl)pιperazιne; NMR (CDCI 3 ) 7.2 (m, 4), 7.0 (t, 2), 6.8 (dd, 2), 5.7 (br s, 1 ), 5.2 (m, 1 ), 5.0 (m, 1 ), 4.8-2.0 (m, 15) ppm; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(Λ/'-(ethoxycarbonylmethyl) ureιdo)methyl)pιperazιne; NMR (DMSO-d 6 ) 7.3 (m, 4), 7.1 (t, 2), 6 8 (d, 2), 6.5 (t, 2), 4.8 (m, 2), 4.1-1.8 (m, 15), 1.1 (m, 3) ppm; (fraπs)-1-((4-chloro-2-((amιnocarbonyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCl 3 ) 9.8 (br s, 1 ), 8.3 (s, 1 ), 7.3 (m, 2), 7.0 (m, 3), 6.8 (d, 1 ), 6.0 (br s, 1 ), 5.0 (m, 2), 4.8 (m, 2), 4.1 (m, 3), 3.6 (m, 3), 3.1 (m, 2), 2.7 (d, 1 ), 2.3 (d, 1 ), 0.9 (m, 6) ppm; (frans)-1-((4-chloro-2-((amιnocarbonyl)(methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 9.8 (br m, 1 ), 9.4 (s, 1 ), 8 2 (s, 1 ), 7.6 (m, 2), 7.3 (m, 2), 7.0 (m, 2), 6.0 (br m, 2), 5.0 (m, 3), 4.3 (br m, 3), 4 0 (s. 2), 3 7-3.2 (m, 4), 2.8 (s, 3), 1.3 (m, 3), 1 2 ( , 3) ppm, (frans)-1-((4-chtoro-2-(Λ/'-ethyluredιo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, NMR (CDCI 3 ) 8 8 (s, 1 ), 8.4 (s, 1 ), 7.3 (m, 2), 7.0 (m, 2), 6 8 (m, 3), 4 7 (m, 2), 4.1 (m, 2), 3.6-3.3 (m, 4), 3.0 (br s, 1 ), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 5), 0.9 (m, 6) ppm; (frans)-1-((4-chloro-2-(Λ/-(2,4-dιchlorophenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 10 4 (br d, 1 ), 9.2 (s, 1 ), 9.1 (s, 1 ), 8 2 (s, 1 ), 8.1 (d, 1 ), 7 7 (m, 2), 7.3 (m, 3), 6.9 (m, 2), 5.0 (m, 2), 4 7 (m, 1 ), 4.3 (m, 3), 3 8 (q, 1 ), 3.6 (m, 1 ), 3.4 (m, 1 ), 2.9 (t, 1 ), 1.4 (m, 3), 1.2 (m, 3) ppm; (frans)-1-((4-chloro-2-(Λ/'-(4-nιtrophenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- 4- fluorobenzyOpiperazme, NMR (CDCI 3 ) 9 1 (s, 1 ), 8 4 (s, 1 ), 8.3 (s, 1 ), 8.2 (s, 1 ), 7 9 (d, 1 ), 7.8 (d, 1 ), 7.3 (m, 3), 7.0 (t, 2), 6.8 (d, 1 ), 6.7 (m, 1 ), 4 7 (m, 2), 3.6 (m, 4), 3 1 (m, 1 ), 2.8 (m, 1 ), 2.3 (d, 1 ), 1.4 (m, 3), 1.0 (m, 3) ppm; (fraπs)-1-((4-chloro-2-(Λ/-(4-methylphenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (DMSO-d 6 ) 10.5 (br d, 1 ), 9.6 (s, 1 ), 8.5 (d, 1 ), 8.2 (s, 1 ), 7.8 (m, 2), 7.3 (m, 4), 7.1 (d, 2), 6.9 (s, 1 ), 5.0 (m, 2), 4.3 (m, 3), 3.9 (s, 1 ), 3.6 (m, 1 ), 3 4 (m, 1 ), 2.8 (dd, 1 ), 2.2 (s, 3), 1.4 (m, 3), 1.2 (m, 3) ppm; (frar.s)-1-((4-chloro-2-(Λ '-benzyiureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 9.0 (s, 1 ), 8.4 (s, 1 ), 7.3 (m, 8), 7.0 (t, 2), 6 8 (q, 2), 5.6 (t, 1 ), 4.6 (m, 4), 3.6 (m, 3), 3.0 (m, 1 ), 2.7 (m, 1 ), 2.2 (m, 2), 1.3 (m, 3), 0 9 (m, 3) ppm; (fΛaΛ?s)-1-((4-chloro-2-(1-(Λ/-methyl-Λ '-ethylureιdo)ethyl)phenoxy)methyi)carbonyl-2,5-dιmethyl- 4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 1 ), 5.6 (m, 1 ), 5.4 (br d, 1 ) 4.7 (m, 2), 3.5 (q, 2), 3.2 (m, 4), 3.0 (m, 1 ), 2.7 (m, 4), 2.2 (d, 1 ), 1.4 (d, 3), 1.3 (m, 9), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-(oxazol-2-ylamιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 3), 7.2 (dd, 1 ), 7.0 (t, 2), 6.8 (d, 1 ), 4.7 (m, 3), 4.4 (s, 2), 4.3 (t, 2), 3.9 (m, 1 ), 3.8 (t, 2), 3.5 (q, 2), 3.3 (m, 1 ), 3.0 (m, 1 ), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (fraπs)-1-(2-(4-chlorophenyl)-3-(ureido)propyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (DMSO-d 6 ) 7.3 (m, 4), 7.2 (m, 2), 7.1 (t, 2), 5.8 (br s, 1 ), 5 4 (br s, 2), 4.0 (m, 1 ), 3.4 (m, 2), 3.2 (m, 3), 2.9 (m, 1 ), 2.5 (m, 2), 2.1 (m, 1 ), 1 1 (m, 3), 0.8 (m, 3) ppm; (fraπs)-1-(2-(4-chlorophenyl)-2-(ureιdo)ethyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (DMSO-d 6 ) 7.3 (m, 5), 7.1 (t, 2), 6.6 (q, 1 ), 5.6 (br s, 2), 5.0 (m, 1 ), 4 4 (m, 0.5), 4.0 (m, 0.5), 3.5 (m, 2), 3.3 (m, 2), 2.8 (m, 2), 2.7 (m, 1 ), 2.5 (m, 1 ), 2.1 (d, 1 ), 1 2 (m, 3), 0.8 (m, 3) ppm; (frans)-1-((4-chloro-2-((Λ/'-(3-methoxyphenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyl)piperazine; NMR (DMSO-d 6 ) 10 2 (br s, 1 ), 9.5 (s, 1 ), 8.5 (br s, 1 ), 8 2 (s, 1 ), 7 7 (m, 2), 7.2 (m, 4), 7.0 (s, 3), 6.5 (dd, 1 ), 5 0 (m, 2), 4.3 (m, 3), 3.7 (m, 5), 3 4 (m, 1 ), 2.9 (m, 1 ), 1.4 (s, 3), 1.2 (s, 3) ppm; and (frans)-1-((4-chloro-2-((Λ/'-(tπchloromethylcarbonyl)ureιdo)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 10.5 (s, 1 ), 9.0 (m, 1 ), 8.3 (s, 1 ), 7.3 (m, 2), 7.0 (m, 4), 4.8 (m, 3), 4.2 (m, 1 ), 3.6 (m, 2), 3.4 (m, 1 ), 3.0 (m, 1 ), 2 7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm. C. In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 9 Compounds of formula (la) A. To a solution of (c/s)-1-((4-chlorophenoxy)methyl)carbonyl-3,5- dimethylpiperazine (0.20 g, 0.71 mmol) in anhydrous THF (2 mL) was added 4-fluorobenzyl- bromide (0.11 mL, 0.85 mmol), dnsopropylethylamine (0.15 mL, 0.85 mmol) and sodium iodide (0.042 g, 0.28 mmol). The resultant mixture was stirred at ambient temperature for 2 days. At that time the mixture was poured into ether and washed with 5% aqueous NaHC0 3 solution, then brine. The organic layer was dried over MgS0 4 , filtered, and concentrated in vacuo to afford a yellow oil. Purification by flash column chromatography on silica gel afforded 0.17 g of (c/ ' s)-1-((4-chlorophenoxy)methyl)carbonyl-3,5-dimethyl-4-(4-fluorobenzyl)pιperazιne as a pink oil; which was converted to its hydrochoride salt; NMR (CDCI 3 ) 7.6 (m, 2), 7.3 (m, 4), 7.0-6.8 (m, 2), 5.0-2.8 (m, 10), 1.5-1.3 (m, 6) ppm. B. In a similar manner, the following compounds of formula (la) were made: 1 -((4-chlorophenoxy)methyl)carbonyl-2-((((cyclopropyl)methyl)amιno)methyl)-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 4.5 (s, 2), 3.4 (m, 4), 3.0 (m, 1 ), 2.5 (m, 4), 2.2 (t, 1 ), 2.0 (m, 2), 1.6 (s, 2), 0.8 (m, 1 ), 0.5 (m, 2), 0 1 (m, 2) ppm; (3R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3,5-dιmethylpιperazιne, hydrochloride salt; NMR (CDCI 3 ) 13.3 (m,1 ), 7.9 (q, 2), 7.2 (m, 4), 6.9 (d, 2), 6.8 (d, 2), 4.8-3.3 (m, 10), 1.7 (d, 3), 1.2-1.0 (m, 3) ppm; (3S,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3,5-dimethyipιperazιne, hydrochloride salt; NMR (CDCI 3 ) 13.3 (m,1 ), 7.9 (q, 2), 7.2 (m, 4), 6.9 (d, 2), 6.8 (d, 2), 4.8-3.3 (m, 10), 1.7 (d, 3), 1.2-1.0 (m, 3) ppm; 1 -((4-chlorophenoxy)methyl)carbonyl-2-(((4-fluorobenzyl)amιno)methyl)-4-(4- fluorobenzyOpiperazme; 1-((4-chlorophenoxy)methyl)carbonyl-2-(((methyl)amιno)methyl)-4-(4- fluorobenzyOpiperazme: NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.8 (d, 2), 4.5 (q, 2), 3.6 (m, 4), 3.1 (m, 2), 2.8 (m, 3), 2.6 (s, 3), 2.5-2.3 (m, 3) ppm; and 1 -((4-chiorophenoxy)methyl)carbonyl-3-trifluoromethyl-4-(4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6.8 (dd, 2), 4.6 (m, 2), 4.2 (m, 1 ), 3.8 (m, 3), 3.6 (dd, 1 ), 3.3 (m, 2), 3.0 (m, 1 ), 2.6 (m, 1 ) ppm. C. In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 10 Compounds of formula (lc) A. To a solution of 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4- (benzyl)pιperazιne (0.15 g, 0.37 mmol) in toluene (10 mL) was added iodomethane (0.15 mL, 2.2 mmol). The resultant mixture was stirred at ambient temperature for 4 days. At that time the solid precipitate was filtered and washed with ether to afford 0.019 g of 1 -((3,4,5- tπmethoxyphenoxy)methyl)carbonyl-4-methyl-4-(benzyl)pιperazιnιum iodide as a white solid; NMR (DMSO-d 6 ) 7.6 (s, 5), 6.3 (s, 2), 4.8 (s, 2), 4.7 (s, 2), 4.2 (d, 1 ), 4.0 (d, 1 ), 3.8 (s, 6), 3.6- 3.3 (m, 9), 3.1 (s, 3) ppm. B. In a similar manner, other compounds of formula (lc) were made. 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-methyl-4-(4-fluorobenzyl)pιperazιnιum iodide, NMR (DMSO-d 6 ) 7.6 (dt, 2), 7.4 (t, 2), 6.3 (s, 2), 4.8 (s, 2), 4.7 (s, 2), 4.2 (d, 1 ), 4.0 (d, 1 ), 3.8 (s, 6), 3.6-3.3 (m, 9), 3.0 (s, 3) ppm; 1 -((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-4-(prop-2-enyl)-4-(4-fluorobeπzyl)pιperazιnιum bromide; NMR (DMSO-d 6 ) 7.6 (dt, 2), 7 4 (t, 2), 6.2 (m, 3), 5.75 (d, 1 ), 5.65 (d, 1 ), 4.8 (s, 2), 4 7 (s, 2), 4.2-3.3 (m, 19) ppm; 1 -((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-benzyl-4-(4-fluorobenzyl)pιperazιnιum bromide, NMR (DMSO-d 6 ) 7.7-7.1 (m, 9), 6.2 (s, 2), 4.8 (m, 6), 4.0-3.3 (m, 17) ppm; and 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-2,4-dιmethyl-4-(4-fluorobenzyl)pιperazιnιum iodide; NMR (DMSO-d 6 ) 7.6 (m, 2), 7.2 (m4), 7.0 (d, 2), 4 9 (s, 2), 4.6 (s, 2), 3.6-3 3 (m, 7), 3.1 (s, 2), 2.9 (s, 1 ), 1.2 (m, 3) ppm. C. In a similar manner, other compounds of formula (lc) are made. EXAMPLE 11 Compounds of Formula (la) A. To a solution of 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-2- (methoxycarbonyl)methyl-4-(4-fluorobenzyl)pιperazιne (0.20 g, 0.42 mmol) in a methanol/water solution (20 mL, 3:1 ) was added lithium hydroxide, monohydrate (0.40 mL, 9.5 mmol). The resultant mixture was stirred at ambient temperature for 30 mm. At that time HPLC analysis showed complete conversion had occurred. The mixture was poured into ethyl acetate and washed sequentially with an aqueous acetic acid/water solution (pH < 4), water, and brine The organic layer was separated, dried over MgS0 , filtered and concentrated in vacuo to afford 0.060 g of 1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-2-(carboxy)methyl-4-(4- fluorobenzyOpiperazme as a white solid; NMR (CDCI 3 ) 7 4 (m, 2), 7.1 (m, 2), 6.2 (m, 2), 5 1 (m, 1 ), 4 7 (m, 3), 4.0 (m, 2), 3.8 (d, 9), 3.3-3.1 (m, 4), 2.6 (m, 2), 2.4 (m, 2) ppm, MS (ESI) 476. B. In a similar manner, the following compounds of the invention were made- 1-((4-chlorophenoxy)methyl)carbonyl-3-(carboxy)methyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 7.4 (t, 2), 7.3 (d, 2), 7 1 (t, 2), 6.9 (d, 2), 4.7 (m, 2), 4.0 (d, 2), 3 7 (m, 2), 3.5 (m, 3), 3.2 (m, 1 ), 2.8-2.4 (m, 3) ppm; 1 -((4-chloro-2-carboxyphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 8.0 (s, 1 ), 7.4 (dd, 1 ), 7.3 (m, 3), 7.0 (t, 1 ), 6.9 (d, 1 ), 5.0 (m, 2), 4.6 (m, 1 ), 4 3 (m, 1 ), 3 7 (m, 1 ), 3.4 (m, 2), 2.8 (d, 1 ), 2.6 (m, 1 ), 2 1 (m, 1 ), 1.4 (d, 1.5), 1.3 (d, 1 5) ppm; and (fraπs)-1-((4-chloro-2-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 9.4 (br s, 1 ), 8.0 (m, 1 ), 7.5 (m, 3), 7.2 (m, 2), 7.0 (d, 1 ), 5.0 (m, 2), 4.6 (m, 1 ), 4.3 (m, 3), 3.7 (m, 2), 3 4 (m, 1 ), 3.3 (m, 1 ), 1 4-1 3 (m, 6) ppm C In a simitar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made EXAMPLE 12 Compounds of formula (la) A To a solution of lithium aluminum hydride (0.29 g, 7 mmol) in a solution of anhydrous THF (16 mL) was added 1-((4-chlorophenoxy)methyl)carbonyl-4-(4- fluorobenzyOpiperazine (0.36 g, 1.0 mmol, in 3 mL of THF). The resultant mixture was stirred at ambient temperature for 9 hours. At that time 0.3 mL of water and 0.3 mL of 15% aqueous NaOH solution were added and the resulting mixture stirred at ambient temperature. After 18 hours, the mixture was filtered through a short column of Celite (THF) and the filtrate concentrated in vacuo to afford 0.12 g of 1-(2-(4-chlorophenoxy)ethyl)-4-(4- fluorobenzyOpiperazine as a clear oil; NMR (CDCI 3 ) 7.2 (m, 4), 7.0 (m, 2), 6.8 (m, 2), 4 0 (m, 2), 3 4 (m, 2), 2.8-2.4 (m, 10) ppm. B. In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 13 Compounds of Formula (lb) A. To a solution of 1-(1-(f-butoxycarbonyl)amιno-2-(4-chlorophenyl)ethyl)carbonyl-4- (benzyl)pιperazιne (0.20 g, 0.44 mmol) in a solution of CH 2 CI 2 (3 mL) was added trifluoroacetic acid (3 mL). The resultant mixture was stirred at ambient temperature. After 18 hours, the mixture was concentrated in vacuo to afford a yellow oil. This was dissolved in ethyl acetate and wasned with an aqueous NaHC0 3 solution. The organic layer was separated, dried over MgS0 4 , filtered and concentrated in vacuo to afford 0.17 g of a clear, colorless film. This was dissolved in ether and treated with an ethereal solution of HCI, resulting in formation of a white precipitate. Concentration afforded 0.18 g of 1-(1-amιno-2-(4-chlorophenyl)ethyl)carbonyl-4- (benzyl)pιperazιne as a white solid; NMR (CDCI 3 ) 7.4 (m, 7), 7.1 (m, 2), 4.0 (t, 1 ), 3.7-3.1 (m, 4), 2.8 (m, 2), 2.4-2.2 (m, 5), 1.8 (m, 1 ) ppm B. In a similar manner, the following compounds of formula (lb) were made: 1-(3-amιno-2-(4-chiorophenyl)propyi)carbonyl-4-(4-chlorobenzyl)pιperazιne; NMR (CDCI 3 ) 7.2 (m, 8), 3.8 (s, 3), 3.6-3.3 (m, 8), 3.0 (m, 2), 2.6 (dq, 2), 2.4-2.1 (m, 4) ppm; and 1 -(1 -amιno-2-(4-chlorophenyl)ethyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; NMR (CDCI 3 ) 7 3 (m, 6), 7.1 (d, 2), 4.0 (t, 1 ), 3.6-3.1 (m, 6), 2.8 (dq, 2), 2.6 (br s, 2), 2.4 (m, 3), 1.8 (m, 1 ) PPm. C. In a similar manner, the following compounds of formula (la) were made: (fraπs)-1-((4-chloro-2-(amιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (CDCI 3 ) 7.3 (m, 3), 7.2 (dd, 1 ), 7.0 (t, 2), 6.8 (br d, 1 ), 4.7 (m, 2), 3.9 (s, 2), 3.5 (m, 3), 3.0 (br s, 1 ), 2.7 (m, 1 ), 2.2 (m, 4), 1.3 (m, 3), 0.9 (m, 3) ppm; (frans)-1-((4-chloro-2-(giycinamido)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 10.1 (s, 1 ), 8.5 (s, 1 ), 7.3 (t, 3), 7.0 (t, 3), 6.8 (d, 1 ), 4.7 (m, 3), 4.2-3.4 (m, 5), 3.2 (m, 1 ), 3.0 (br s, 1 ), 2.7 (dd, 1 ), 2.2 (d, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; (2R,5S)-1-((4-chioro-2-(glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; NMR (DMSO-d 6 ) 10 0 (s, 1), 8.2 (m, 3), 7.6 (s, 1), 7.3 (m, 2), 7 1 (dd, 1 ), 6.9 (m, 1 ), 5.2-4.2 (m, 5), 3.8-2.9 (m, 7), 1.2 (m, 6) ppm; (2R)-1-((4-chloro-2-(glycιnamιdo)phenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazine; NMR (DMSO-d 6 ) 11 4 (br s, 1 ), 10.0 (s, 1 ), 8.3 (br s, 2), 8 1 (s, 1 ), 7.8 (m, 2), 7.4 (t, 2), 7 1 (d, 1 ), 7.0 (d, 1 ) 5.0 (q, 2), 4.7 (m, 1 ), 4 3 (m, 3), 3.9 (m, 3), 3.6 (m, 1 ), 3.1 (m, 3), 1.5 (d, 1.5), 1.3 (d, 1.5) ppm; (frans)-1-((4-chloro-2-((Λ/'-methylglycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 9.9 (s, 1 ), 8.5 (s, 1 ), 7.3 (m, 3), 7.0 (m, 3), 6 8 (d, 1 ), 4 7 (m, 3), 4 2-3.9 (m, 1 ), 3.6-3.3 (m, 5), 3 0 (br s, 1 ), 2.7 (dd, 1 ), 2.5 (s, 3), 2 3 (d, 1 ), 1.3 (m, 3), 1.0 (m, 3) ppm, (frans)-1-((4-chloro-2-(alanιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, NMR (CDCI 3 ) 10.2 (s, 1 ), 8.5 (s, 1 ), 7.3 (m, 3), 7 0 (m, 3), 6 8 (d, 1 ), 4.7 (m, 3), 4.2-3.9 (m, 1 ), 3.6-3.2 (m, 5), 3 0 (m, 1 ), 2 7 (dd, 1 ), 2.2 (d, 1 ), 1 4 (d, 3), 1 3 (m, 3), 1.0 (br s, 3) ppm; (frat7s)-1-((4-chloro-2-(1-(methylamιno)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, NMR (CDCI 3 ) 7 3 (m, 3), 7 1 (dd, 1 ), 7.0 (t, 2), 6 8 (br d, 1 ), 4 7 (m, 3), 4 0 (q, 2), 3.6 (q, 2), 3.2 (m, 1 ), 3 0 (m, 1 ), 2 7 (dd, 1 ), 2.3 (m, 4), 1 3 (m, 6), 0 9 (m, 3) ppm, (fraπs)-1 -((4-chloro-2-((methylamιno)(phenyl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 7 6 (br d, 1 ), 7 4-7 1 (m, 8), 7 0 (t, 2), 6 8 (m, 1 ), 5.0 (d, 1 ), 4.6 (m, 3), 4.2 (m, 1 ), 3.5 (t, 1 ), 3 4-3.0 (m, 4), 2.8 (m, 1 ), 2 4 (s, 3), 2.2 (m, 1 ), 1.2 (m, 3), 0.8 (m, 3) ppm; (2R)-1-((4-chloro-2-((pιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazmeNMR (DMSO-d 6 ) 9.2 (br s, 1 ), 7 6 (m, 4), 7.3 (t, 2), 7 2 (d, 1 ), 5 2 (dd, 1 ), 5.0 (d, 1 ), 4.8 (m, 1 ), 4.4 (d, 4), 3.9 (d, 1 ), 3 4 (m, 1 1 ), 1 4 (d, 1.5), 1.2 (d, 1 5) PPm, (2R,5S)-1-((4-chloro-2-((pιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; NMR (DMSO-d 6 ) 9.8 (br s, 1 ), 9.2 (br s, 1 ), 7.6 (s, 3), 7.5 (dd, 1 ), 7.3 (t, 2), 7.2 (d, 1 ), 5 4 (m, 1 ), 5.0 (m, 3), 4 7 (m, 1 ), 4.5 (s, 2), 4 3 (m, 3), 3 7-3 1 (m, 11 ), 1 4-1 1 (m, 6) ppm; (frans)-1-((4-chloro-2-((pιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; NMP (DMSO-d 6 ) 1 1.3 (br d, 1 ), 9.7 (m, 2), 7.9 (m, 2), 7.7 (m, 2), 7.4-7.2 (m, 3), 5.4 (m, 1 ), 5.0 (m, 2), 4.6 (m, 1 ), 4.2 (m, 3), 3.8-3.2 (m, 10), 2.8 (dd, 1 ), 1.7 (m, 3), 1.4 (dd, 3), 1.2 (m, 3) ppm; (frans)-1-(2-(4-chlorophenyl)-3-(ammo)propyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 4), 7.2 (d, 2), 7.0 (t, 2), 4.8 (m, 1 ), 4.2 (m, 1 ), 3.9 (m, 1 ), 3.5-3.2 (m, 3), 2.9 (m, 3), 2.6 (m, 2), 2.2 (m, 1 ), 1.2 (m, 3), 0.8 (m, 3) ppm; and (frans)-1-(2-(4-chlorophenyl)-2-(amιno)ethyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, NMR (CDCI 3 ) 7.3 (m, 6), 7.0 (t, 2), 4.7 (m, 0.5), 4.5 (m, 1 ), 4.2 (d, 0.5), 3.5 (q, 2), 3.2 (m, 1 ), 3.0 (m, 1 ), 2.6 (m, 2), 2.5 (m, 2), 2.2 (m, 1 ), 1.2 (m, 3), 0.9 (m, 3) ppm D. In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 14 Compounds of Formula (la) A. To a solution of (fraπs)-1-((4-chloro-2-carboxyphenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne (0.217 g, 0.50 mmol) in a solution of tetrahydroduran (5 L) at 0°C was added isobutyl chloroformate (0 075 g, 0 55 mmol) and /V-methylmorpholιne (0.0556 g, 0.55 mmol) The resulting mixture was stirred at 0°C for 20 mm, resulting in formation of a white precipitate. A solution of methylamme in tetrahydrofuran (0.25 mL, 2.0 M, 0.50 mmol) was then added and the mixture stirred for 30 m more, at which time it was concentrated of volatiles in vacuo. The resulting residue was dissolved in ethyl acetate and washed with water, then brine, dried over MgS0 4 , filtered and concentrated to 0.208 g of a foam. This was dissolved in ethyl acetate and treated with 1 M ethereal HCI solution (excess) The resulting solid was collected by filtration and washed with ethyl acetate. Drying in vacuo afforded 0.19 g of (frans)-1-((4-chloro-2-(methylamιnocarbonyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazine as a white solid; NMR (DMSO-d 6 ) 10.8 (br d, 1 ), 9.2 (br s, 1 ), 7.8 (s, 2), 7.7 (m, 1 ), 7.6 (m, 1 ), 7.3 (m, 3), 5.4 (d, 1 ), 5.0 (m, 2), 4.7 (m, 1 ), 4.3 (m, 3), 4.0 (m, 1 ), 3.6 (m, 2), 2.8 (s, 3), 1.4 (m, 3), 1.3 (m, 3) ppm. B. In a similar manner, the following compounds of formula (la) were made: (fraπs)-1-((4-chloro-2-((amιnocarbonylmethyl)amιnocarbonyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobeπzyl)piperazιne; NMR (DMSO-d 6 ) 9.4 (br s, 1 ), 7.8 (s, 1 ), 7.6 (dd, 1 ), 7.4 (m, 2), 7.2 (d, 1), 7.1 (t, 2), 7.0 (s, 1 ), 5.3 (m, 1 ), 5.0 (m, 2), 4.4 (m, 1 ), 4.0 (m, 1 ), 3.8 (d, 2), 3.5 (m, 2), 3.0 (m, 1 ), 2.7 (m, 1 ), 2.2 (br d, 1 ), 1.2 (br d, 3), 0.9 (br d, 3) ppm; (frat7s)-1-((4-chloro-2-((2-amιnoethyl)amιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; NMR (CDCI 3 ) 9.4 (br s, 1 ), 8.2 (s, 1 ), 7.3 (m, 3), 7.0 (t, 2), 6.8 (d, 1 ), 4.7 (m, 3), 4.2 (m, 1 ) 3.6 (m, 5), 3.1 (m, 3), 2.7 (br d, 1 ), 2.3 (d, 1 ), 1.3 (br d, 3), 1.0 (m, 2) ppm; (frans)-1-((4-chloro-2-((4-aminocarbonylphenyl)aminocarbonyl)phenoxy)methyl)carbonyl-2.5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; NMR (DMSO-d 6 ) 1 1.4 (s, 1 ), 7.9 (m, 5), 7 7 (d, 1 ), 7.4 (m, 3), 7.1 (t, 2), 5.4 (d, 1 ), 5.1 (m, 2), 4.6 (br s, 1 ), 4.0 (m, 1 ), 3.5 (m, 3), 3.0 (m, 1 ), 2.2 (m, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm; and (fraπs)-1-(2-(4-chlorophenyl)-3-(f-butoxycarbonylamιno)propyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; NMR (CDCI 3 ) 7.3 (m, 4), 7.2 (d, 2), 7.0 (t, 2), 4.8 (br s, 1 ), 4.6 (m, 1 ), 4.0 (m, 1 ), 3.4 (m, 6), 3.0 (m, 1 ), 2.6 (m, 2), 2.1 (m, 1 ), 1.4 (s, 9), 1.2 (m, 3), 0.9 (m, 3) ppm. C In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are prepared EXAMPLE 15 Compounds of formula (la) A. To a solution of hydroxylamine, hydrochloride (0.17 g, 2.5 mmol) in DMSO (3 mL) was added triethylamme (0.252 g, 2.5 mmol). The mixture was stirred at ambient temperature for 10 minutes, then filtered and washed with THF. The filtrate was concentrated in vacuo to remove the THF then treated with (frans)-1-((4-chloro-2- cyanophenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)pιperazιne (0.200 g, 0.48 mmol) The resulting mixture was heated to 75°C for 20 hours. At that time the mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with water, then brine, dried over MgS0 , filtered concentrated in vacuo to afford 0.21 g of an oil. 0.030 g of this oil was dissolved in ethyl acetate and treated with 1 M ethereal HCI solution (excess). The resulting soiid was collected by filtration and washed with ethyl acetate. Drying in vacuo afforded 0.027 g of (frans)-1-((4-chloro-2-(hydroxyamιdino)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazine as a white solid; NMR (CDCI 3 ) 7.6 (s, 1 ), 7.3 (t, 2), 7.2 (dd, 1 ), 7.0 (t, 2), 6.7 (br d, 1 ), 6.1 (br s, 2), 4.7 (m, 3), 3.7 (br d, 1 ), 3.5 (q, 2), 3.2 (m, 1 ), 3 0 (m, 1 ), 2.7 (m, 1 ), 2.2 (t, 1 ), 1.3 (m, 3), 0.9 (m, 3) ppm. B. In a similar manner, other compounds of formulae (la), (lb), (lc) and (Id) are made. EXAMPLE 16 Compounds of Formula (la) A To a solution of 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2- hydroxyethyOpiperazine (0.134 g, 0.33 mmol) and tπphenylphosphine (0.100 g) in THF (6 mL) at 0°C was added diethyl azodicarboxylate (0.060 mL) and diphenylphosphoryl azide (0.081 mL). The mixture was stirred at ambient temperature for 2 days, then concentrated of volatiles in vacuo. Purification by flash column chromatography on silica gel afforded 0.047 g of 1-((4- chlorophenoxy)methyl)carbonyl-2-(2-azιdoethyl)-4-(4-fluorobenzyl)pιperazιne as a clear, colorless oil; NMR (CDCI 3 ) 7.3 (m, 4), 7.0 (t, 2), 6 9 (d, 2), 4.7 (m, 3), 4.4 (br d, 1 ), 4.3 (m, 1 ), 4 1 (m, 1 ), 3.5-3 1 (m, 4), 2.8 (d, 1 ), 2.7 (d, 1 ), 2.1 (m, 2), 1.8 (m, 1 ) ppm. B. In a similar manner, the compounds of formula (la), (lb), (lc) and (Id) are made EXAMPLE 17 Compounds of Formula (la) A. To a solution of (frans)-1-((4-chloro-2-amιnophenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne (0.169 g, 0 416 mol) in 10 mL of methylene chloride was added phthaliic anhydride (0.074 g, 0.499 mol) and several 4A molecular sieves. The mixture was stirred at ambient temperature for 3 hours, then at 70°C for 3 hours. At that time the mixure was cooled to 0°C and treated with oxalyl chloride (0.064 g, 0.499 mol). This was stirred at ambient temperature for 3 hours then partitioned between methylene chloride and water. The organic layer was concentrated to give an oil. Purification by flash column chromatography on silica gel afforded 0.058 g of a clear oil. This was dissolved in ethyl acetate and treated with 1 M ethereal HCI solution (excess). The resulting solid was collected by filtration and washed with ethyl acetate. Drying in vacuo afforded 0.045 g of (frat?s)-1-((4- chloro-2-(phthaiιmιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne as a white solid, NMR (CDCI 3 ) 7.9 (m, 2), 7.8 (m, 2), 7 4 (d, 1 ), 7.3 (m, 3), 7.05 (d, 1 ), 7 0 (t, 2), 4 6 (m, 3), 4 0 (m, 1 ), 3.5 (m, 1 ), 3 4 (m, 2), 2.9 (m, 1 ), 2.6 (m, 1 ), 2.2 (m, 1 ), 1 2 (m, 3), 0 9 (m, 3) pppm B In a similar manner, the following compound of formula (la) was made (frans)-1-((4-chloro-2-(maleιmιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, NMR (CDCI 3 ) 7 3 (m, 6), 7.0 (t, 2), 6.8 (s, 1 ), 4 6 (m, 3), 4 0 ( , 1 ), 3.5 (q, 2), 3.2 (m, 1 ), 3 0 (br s, 1 ), 2 6 (dd, 1 ), 2.2 (br d, 1 ), 1 2 (m, 3), 0 9 (m, 3) ppm C In a similar manner, compound of formula (la), (lb), (lc) and (Id) are made EXAMPLE 18 This example illustrates the preparation of representative pharmaceutical compositions for oral administration containing a compound of the invention, or a pharmaceutically acceptable salt thereof, e.g., 1-((2-methylphenoxy)methyl)carbonyl-4-(4- chlorobenzyOpiperazme hydrochloride salt A Ingredients % wt./wt Compound of the invention 20.0% Lactose 79.5% Magnesium stearate 0.5% The above ingredients are mixed and dispensed into hard-shell gelatin capsules containing 100 mg each, one capsule would approximate a total daily dosage B Ingredients % wt./wt Compound of the invention 20.0% Magnesium stearate 0.9% Starch 8.6% Lactose 69.6% PVP (polyvmylpyrrolidine) 0.9% The above ingredients with the exception of the magnesium stearate are combined and granulated using water as a granulating iiquid. The formulation is then dried, mixed with the magnesium stearate and formed into tablets with an appropriate tablet g machine. C. Ingredients Compound of the invention 0.1 g Propylene glycol 20.0 g Polyethylene glycol 400 20.0 g Polysorbate 80 1.0 g Water q.s. 100 mL The compound of the invention is dissolved in propylene glycol, polyethylene glycol 400 and polysorbate 80. A sufficient quantity of water is then added with stirring to provide 100 mL of the solution which is filtered and bottled. D. Ingredients % wt./wt. Compound of the invention 20.0% Peanut Oil 78.0% Span 60 2.0% The above ingredients are melted, mixed and filled into soft elastic capsules E Ingredients % wt./wt Compound of the invention 1.0% Methyl or carboxymethyl cellulose 2.0% 0.9% saline q.s. 100 mL The compound of the invention is dissolved in the cellulose/saline solution, filtered and bottled for use. EXAMPLE 19 This example illustrates the preparation of a representative pharmaceutical formulation for parenteral administration containing a compound of the invention, or a pharmaceutically acceptable salt thereof, e.g., 4-(4-fluorobenzyl)-1-((2-((acetylamιno)methyl)-4- chlorophenoxy)methyl)carbonyl-2,5-methyipiperazιne: Inαredients Compound of the invention 0.02 g Propylene glycol 20.0 g Polyethylene glycol 400 20.0 g Polysorbate 80 1.0 g 0.9% Saline solution q.s. 100 mL The compound of the invention is dissolved in propylene glycol, polyethylene glycol 400 and polysorbate 80. A sufficient quantity of 0.9% saline solution is then added with stirring to provide 100 mL of the IN. solution which is filtered through a 0.2 m membrane filter and packaged under sterile conditions EXAMPLE 20 This example illustrates the preparation of a representative pharmaceutical composition in suppository form containing a compound of the invention, or a pharmaceutically acceptable salt thereof, e.g., 4-(4-fluorobenzyl)-1-((4-chiorophenoxy)methyl)carbonyl-2-(2- hydroxyethyOpiperazine: Ingredients % wt./wt Compound of the invention 1.0% Polyethylene glycol 1000 74.5% Polyethylene glycol 4000 24.5% The ingredients are melted together and mixed on a steam bath, and poured into molds containing 2.5 g total weight. EXAMPLE 21 This example illustrates the preparation of a representative pharmaceutical formulation for insufflation containing a compound of the invention, or a pharmaceutically acceptable salt thereof, e.g., (2R,5R)-4-(4-fluorobenzyl)-1 -((4-chlorophenoxy)methyl)carbonyl-2,5- dimethylpiperazme- Ingredients % wt /wt Micronized compound of the invention 1.0% Micronized lactose 99.0% The ingredients are milled, mixed, and packaged in an insufflator equipped with a dosing pump EXAMPLE 22 This example illustrates the preparation of a representative pharmaceutical formulation in nebulized form containing a compound of the invention, or a pharmaceutically acceptable salt thereof, e g , 1-(((4-chiorophenyl)amιno)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne Ingredients % wt /wt Compound of the invention 0 005% Water 89.995% Ethanol 10.000% The compound of the invention is dissolved in ethanol and blended with water The formulation is then packaged in a nebulizer equipped with a dosing pump EXAMPLE 23 This example illustrates the preparation of a representative pharmaceutical formulation in aerosol form containing a compound of the invention, or a pharmaceutically acceptable salt thereof, e g , 1-((4-chloro-2-(((ethyl)amιno)methyl)phenoxy)methyl)carboπyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme Ingredients % wt./wt Compound of the invention 0.10% Propellant 11/12 98.90% Oleic acid 1.00% The compound of the invention is dispersed in oleic acid and the propellants The resulting mixture is then poured into an aerosol container fitted with a metering valve * * * * * In the following examples, 293MR celis are utilized. These are human embryonic kidney cells (HEK293) which were stably transfected to express human CCR1 receptor by the following procedure: HEK293 cells were obtained from the American Type Culture Collection (ATCC CRL 1573). Human CCR1 cDNA was provided through collaboration with Dr. Stephen Peiper of the University of Louisville, Kentucky. The CCR1 gene was subcloned using standard techniques (see, e.g., Molecular Cloning: A Laboratory Manual, 2nd Edition, Cold Spring Harbor Laboratory Press, 1989) into a standard plasmid containing the SV40 promoter and enhancer. The piasmid also contained hygromycin and puromycin resistance genes. Calcium phosphate transfection standard protocols were used to insert the plasmid into the HEK293 cells. Cells were selected for stable expression of CCR1 using hygromycin and puromycin selection. Celis were tested for the ability to bind 125 l-labelled RANTES or MIP-1 α with high affinity. EXAMPLE 24 In Vitro Assay: Calcium Flux Since the CCR1 receptor, in common with other seven transmembrane G-protein coupled receptors, responds to the binding of its ligand, e.g., MIP-1 α and RANTES, by mobilizing free intracellular calcium, one can measure biological activity by calcium flux assays using the fluorescent dye Fura 2. In the following assay, the ability of the compounds of the invention to block this biologic response is measured. Protocol: 1 ) Two flasks of 293MR ceils were detached, washed and resuspended in Hanks Ca 2" (50 mL Hanks, 1.0 mL 1 M Hepes, 1.6 mL 500 mM CaCI , pH 7.4). The cells were washed twice in this media. 2) The cells were counted CCR1 = 28 x 10 6 cells made to 2 x 10 6 cells/mL by suspending into 14 mL Hanks Ca 2+ . 3) To 10 mL of the cells (20 x 10 6 ) was added 30 mL of media (containing 50 μg of Fura in 50 μL of DMSO). Final cell concentration was 1.0 x 10 6 ceils/mL. Final Fura concentration was 1.25 μM. 4) The cells were incubated at 37°C for 30 minutes in the presence (or absence) of increasing concentrations of compounds of the invention. Cells were washed as above to remove free Fura. Cells were resuspended at 1 x 10 6 cells/mL. Cells were then aliquoted (2.0 mL) in a cuvette and placed in a spectrofluorimeter The cells were then stimulated with either MIP-1 a or RANTES (Peprotech Inc.) and Ca 2+ release was measured in the spectrofluorimeter. 5) The data were corrected for nM Ca 2+ released by adding 100 μL of 0 1% Triton X-100 (for maximum values) followed by 100 μL of 500 mM EGTA, pH 8.5 (for minimum values) The compounds of the invention, when tested in this assay, demonstrated the ability to inhibit the Ca 2+ mobilization in response to binding of MIP-1 α and RANTES to the CCR1 receptor EXAMPLE 25 In Vitro Assay The assays were performed in a microphysiometer to investigate the functional activity of the antagonist of interest. The microphysiometer assesses cellular response through the use of a silicon-based potentiometπc sensor that can measure small changes on solution pH (Hafeman et ai, Science (1988), Vol. 240, pp 1 182-1 185, Parce et al., Science (1989), Vol 246, pp. 243-247) It has been shown that the microphysiometer can be used for measuring metabolic rates of living cells (Parce et al , 1989) The activation of cell membrane receptors can alter the rate of extracellular acidification (Owicki ef al , Proc. Natl Acad. Sci (1989), Vol 87, pp. 4007-4011 ) The following assay demonstrates that activation of CCR1 receptors endogenously expressed on human THP-1 cells with MIP-1 α and RANTES induced physiological changes resulting in an increase in metabolic rates and that the compounds of the invention inhibit this effect in a dose-dependent manner Materials: 1 Cytosensor Capsule Kit (Molecular Devices Cat #R8013). 2 Agarose Entrapment Medium (Molecular Devices Cat # R8023) 3 Cytosensor Modified RPM I 1640 Medium, low buffered (Molecular Devices Cat #R8023) 4 Cytosensor Steπlant Kit (Molecular Devices Cat# R8017) 5 Reference Electrode Maintenance Kit (Molecular Devices Cat# 0310-2805) 6 MIP-1 α or RANTES (Peprotech inc ) working solution 10 μM in Modified RPMI 1640 medium (Molecular Devices Cat# R8016) supplemented with 1 mg/mL BSA (bovine serum albumin), 100 units/mL penicillin, and 100 μg/mL streptomycin) This working solution is hereinafter referred to as "modified culture medium" 7 MCP-1 working solution 10 μM in modified culture medium 8 Compounds of the invention stock solution 1 mM in DMSO (stored at ambient temperature) 9 Cell Culture a THP-1 (ATCC Cat #TIB202) b Tissue culture medium RPMI 1640 supplemented with 10% FBS (fetal bovine serum) This medium is hereinafter referred to as "growth medium" Assay Procedure THP-1 cells were grown in T-25 cm 2 flasks in growth medium at 37° C, 5 0% C0 2 , 95% air to a cell density of 1x10 6 cells/mL The cells were harvested by centrifugation (5 minutes at 20 G) and resuspended in modified growth medium Trypan blue dye exclusion cell count was performed and cells were > 90% viable Cells were centπfuged again, the supernatant was removed, and the resulting pellet was resuspended to final cell concentration of 1 x 10 6 /0 1 mL Agarose cell entrapment reagent was melted and placed into a 37°C water bath Cell suspension was prepared 0 15 mL of the THP-1 cells were added to a 1 5 mL centrifuge tube with 50 μL of the melted agarose solution Addition to the capsule cups the capsule cups were placed in a 12 well microtiter plate, a spacer was added to the capsule cup, and 7 μL of cell/agarose suspension was pipetted into the center of the cup After three minutes, 1 mL of modified growth medium was pipetted to the outside of the capsule cup, and 200 μL of modified growth medium was pipetted to the inside The capsule insert was then placed into the cup with sterile forceps and 500 μL of modified culture medium was pipetted into the insert Completed capsule were loaded into the chambers of the microphysiometer The chambers were perfused at a rate of 100 μUmmute with modified culture medium The pump cycle was 50 seconds on and 40 seconds off Multiple data points representing metabolic rate were taken and used as baseline Cells were exposed to the compounds of the invention for 30 minutes pπor to addition of chemokine agonists at a final concentration of 10 nM. Treated and non- treated cells were challenged with agonist for 100 seconds and data was collected. When tested in this assay, the compounds of the invention demonstrated the ability to inhibit the activation of the CCR1 receptor by MIP-1 or RANTES EXAMPLE 26 In Vitro Assay In vitro assay for CCR1 receptor antagonists This assay demonstrates the affinities of the compounds of the invention for binding to the CCR1 receptor The binding affinities of the compounds for the CCR1 receptor were determined by their abilities to compete with 125 l-MIP-1 α or 125 I-RANTES for binding to the CCR1 receptor. Reagents and Solutions. MIP-1 a and RANTES (Peprotech Inc.) Cells 293MR cells (K D =1-3 nM and B max =2-3 x 10 6 sites/cell) were detached by trypsinization and plated into flasks at least 48 hours prior to the experiment. Ligand. 125 l-MIP-1 α and 125 I-RANTES from New England Nuclear (specific activity is 2200 Ci/mmol, 25 μCi/vial) was reconstituted in 1 mL H 2 0 Assay buffer 130 mM NaCl, 5 mM KCI, 1 mM MnCI 2 , 50ιτιM Tπs, 30 μg/ml bacitracm, 0 1 % BSA, pH 7 4 Wash buffer Phosphate buffer solution (PBS) Compounds of the Invention: The stock solution of the compounds was 1 mM in 100% DMSO The highest concentration in the assay was 10 μM and may vary depending on the potency of the compounds. A serial 1 3 dilution from the highest concentration was made with assay buffer Six concentrations of each compound were usually being screened to generate a dose curve from which the K, value was determined Assay procedure- Assays were performed in 96-well v-bottom microtiter plates in a total volume of 100 μl 293MR cells was detached from T225 cm 2 flask in PBS by shaking. The cells were washed once in PBS and resuspended in the assay buffer to about 1.1 x 10 5 cells/mL. Cells (about 8000 cells/assay) were incubated with either 125 l-MIP-1 α or 125 I-RANTES (about 15,000- 20,000 cpm/assay) in the presence and absence of different concentrations of compounds at ambient temperature for 30-40 minutes. The reactions were terminated by harvesting through a GF/B filter plate presoaked with 0.3% PEI (Sigma # P-3143) plus 0.5% BSA and washing 5 times with cold PBS. The radioactivities in each well were determined by scmtilation counting following addition of 50 μl of scintillation fluid. The nonspecific binding was defined by the binding in the presence of 100 nM of unlabeied MIP-1 a or RANTES. The CCR1 receptor concentration used in the assay was 0.4 nM and 125 l-MIP-1 α or 125 I-RANTES was 0.06 nM. The concentrations of compounds in the assay is typically from 10 μM to 30 nM in 1 :3 dilution and the concentrations for more potent compounds were lower depending on the potency. Calculations: The dose curves of each compound with 6 concentration points were generated and IC 50 values were determined by fitting the data to the log-logit equation (linear) with an EXCEL spread-sheet. The K, values were then calculated by dividing the IC 50 by 1.025, to correct for concentration of labelled ligand. The compounds of the invention, when tested in this assay, demonstrated their affinity to bind to the CCR1 receptor. * * * * * While the present invention has been described with reference to the specific embodiments thereof, it should be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the true spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation, material, composition of matter, process, process step or steps, to the objective, spirit and scope of the present invention. All such modifications are intended to be within the scope of the claims appended hereto.

Claims: WHAT IS CLAIMED IS: 1 A compound of the following formula (la): wherein: R 1a is one or more substituents independently selected from the group consisting of oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycioalkylaminoalkyl, (cycloalkylalkyl)annιnoalkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylammoalkyl, (alkoxy)aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkylcarboπyl)(alkyl)amιnoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyloxyalkyl, alkoxyalkylcarbonyloxyalkyl aralkoxyalkylcarbonyloxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno, (cycloalkyalkyl)amιnoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkylcarbonyl)(alkyl)amιno, alkylcarbonylammoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyi, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl, R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, ammoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkylamιno)aralkyl, (hydroxyalkyl)hιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylammo, (alkylcarbonyθ(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyaikyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylammoalkyl, (alkoxycarbonyθ(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (aikylsulfony (alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyθ(alkyl)amιnoalkyl, heterocyclylammoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (monoalkylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonyialkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyl)(monoaryl)ureido, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycmamido, aminocarbonylglycmamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyθ(alkyl)glycιnamιdo (alkoxycarbonylamιnoalkyicarbonyl)glycιnamιdo, arylcarbonylglycinamido, (arylcarbonyl)(alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyl)(alkyl)glycιnamιdo, glycinamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, or R 3 is a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonyialkylcarbonyiamino, (alkylcarbonyθ(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, aryicarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido; R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond; R 5 is an alkylene chain or an alkylidene chain, or, if R 4 is a bond, R 5 is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2 , R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond; each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloaikylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylammo, (alkylcarbonyl)(alkyl)amιno, aralkylcarbonylamino, (araikylcarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, aralkylcarbonylaminoalkyl, heterocyclylcarbonylaminoalkyl, (aralkylcarbonyl)(alkyl)amιnoalkyl, arylsulfonylammo, alkylsulfoπylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkyiureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl, provided that when R 4 is -N(R 7 )-, R 3 can not be a heterocyclic ring system containing 4-8 members consisting of carbon atoms and only one nitrogen atom, and as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof 2. The compound of Claim 1 wherein- R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, ammoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloaikylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy )aralkyl, (monoalkylamιno)aralkyl, (hydroxyalkyl)hιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclyicarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl)(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylammoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, alkylsulfonyiaminoalkyl, (alkylsulfonyl)(alkyl)aminoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyclylammoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (monoalkylamιnocarboπylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (aikoxycarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkyiureido, (monoalkyl)(monoaryl)ureιdo, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkyiureidoalkyl, (haloaikyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycmamido, aminocarbonylglycmamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)giycιnamιdo, arylcarbonylglycmamido, (arylcarbonyl)(alkyl)giycinamido, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyl)(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyi)(alkyl)glycιnamιdo, glycinamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl 3 The compound of Claim 2 wherein R 4 is -0-, -N(R 7 )- or -C(R 8 )-, R 5 is an alkylene chain; R 7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonyiammo, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl)(alkyl)amιno, aralkylcarbonylammo, (aralkylcarbonyl)(alkyl)amino, alkylcarbonylammoalkyl, cycloalkylcarbonylammoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoaikyl, aralkylcarbonylaminoalkyl, heterocyclylcarbonylammoalkyl, (aralkyicarbonyl)(alkyl)amιnoalkyl, arylsulfonylammo, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl 4 The compound of Claim 3 wherein R 4 is -0-, R 5 is methylene; and R 6 is -C(O)-. 5 The compound of Claim 4 wherein R 1a is one or more substituents independently selected from the group consisting of halo, alkyl, cycloalkyl, cycioalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, azidoalkyl, monoalkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, hydroxyalkylammoalkyl, aryloxyalkyicarbonyioxyalkyl, aralkoxyaikylcarbonyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen and halo; R 3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, aminoalkoxy, cycloalkyl, cycioalkylaminoalkyl, aralkyl, hydroxyalkyl, (monoalkylamιno)aralkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylammo, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, aikoxycarbonylalkylcarbonylammo, (alkylcarbonyl)(alkyl)amino, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyl)(alkyl)aminoalkyl, arylsulfonylammoalkyl, (arylsulfonyθ(alkyl)amιnoalkyl, heterocyclylammoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (arπιnocarbonylalkyl)amιnocarbonyi, (amιnoalkyl)ammocarbonyl, (hydroxyalkyl)amιnocarbonyl, dialkylaminocarbonylalkyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, (monoalkyθ(monoaryl)ureιdo, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloaikyθ(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglyαnamido, aminocarbonylgiycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonyιamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycinamido, (arylcarbony (alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyθ(alkyl)glycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl 6. The compound of Claim 5 selected from the group consisting of the following compounds: (2S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, 1-((phenoxy)methyl)carbonyl-2-ethyl-4-(4-fluorobenzyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-ethylpιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(methoxymethyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-((acetylamιno)methyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-((4-fluorobenzyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazme; 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-((methyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazine; 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-((2-hydroxyethyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazme; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-((((4-chlorophenoxy)- methyl)carbonyl)oxy)methyl-5-methylpιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(ethoxycarbonyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(methoxycarbonyl)methylpιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-((methoxy)methyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-(methoxy)ethyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxy-2-(4-methylpheny0- ethyOpiperazme; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxypropyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxybut-4-ynyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chiorophenoxy)methyl)carbonyl-5-(2-hydroxy-2- methylpropyOpiperazme; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxyethyl)pιperazιne , 1-((4-chlorophenoxy)methyl)carbonyl-3-(2-((2-hydroxyethyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazine; (c/sJ^-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,3-dιmethylpιperazme, (2S,5R)-1-((4-chloro-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (2S,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,5-dιmethylpιperazιne, (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(2- methylthιo)ethylpιperazιne; (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(benzyloxy)methyl- piperazme; (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-(((2-hydroxyethyl)thιo)methyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chiorophenoxy)methyl)carbonyl-2-(Λ/-(ethoxycarbonylmethyl) ureιdo)methyl)pιperazιne, (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-((amιno)carbonyloxy)methyl-4-(4- fluorobenzyOpiperazine; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-((acetyl)methyl)pιperazιne, (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1- hydroxy-1-(phenyl)methyl)pιperazιne; (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1- hydroxybutyOpiperazme, (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-((dιethylamιno)methyl)pιperazιne, (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-((dιmethylamιno)methyl)pιperazιne, (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-(((cyclopropyl)amιno)methyi)pιperazιne, (2R,5S)-1-((4-chiorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((morpholιn-4- yl)methyl)pιperazιne, (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((pιperazιn-1 - yl)methyl)pιperazιne, (c/s)-1-((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-2,6-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (c/s)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,6-dιmethylpιperazιne, 1-((phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, 1-((2-(acetylamιno)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-hydroxypropyl)-4-(4-fluorobenzyl)pιperazιne, 1-((4-chiorophenoxy)methyl)carbonyl-2-(2-hydroxybut-3-enyl)-4-(4-fluorobenzyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-3-tπfluoromethyl-4-(4-fluorobenzyl)pιperazιne; and (frans)-1-((4-chloro-2-((4-(2,5-dι(tπfluoromethyl)phenylcarbonyl)pιperazιn-1- yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne The compound of Claim 5 wherein R a is one or more substituents independently selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl, azidoalkyi, monoalkylureidoalkyl, aryloxyalkylcarbonyloxyalkyl, and heterocyclylalkyl, R is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, nitro, cyano, ammoalkoxy, cycioalkylaminoalkyl, hydroxyalkyl, (monoalkylamιno)aralkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoaikyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylalkylcarbonylammoalkyl, alkylsulfonylammoalkyl, (alkylsuifonyl)(alkyl)aminoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, (monoalkyl)(monoaryl)ureιdo, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycmamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylalkytcarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylgiycinamido, (arylcarbonyθ(alkyl)glycιnamιdo, (monoaralkyiamιnocarbonyl)(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyl)(alkyl)glycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl 8 The compound of Claim 7 selected from the group consisting of the following compounds: 1 -((3,4,5-tπmethoxyphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-ethylpιperazιne; (2R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-propylpιperazιne, (2S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-propylpιperazιne; 4-(4-fluorobenzyl)-1-(((4-chlorophenoxy)methyl)carbonyl)spιro[cyclopropane-1 I 2'-pιperazιne], 1-((4-chlorophenoxy)methyl)carbonyl-2-hydroxymethyl-4-(4-fluorobenzyl)pιperazιne, 4-(4-fluorobenzyl)-1 -((4-chlorophenoxy)methyl)carbonyl-2-(2-(methoxy)ethyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-((2-methylpropyl)amιno)ethyl)-4-(4- fluorobenzyOpiperazme; 1-((4-chlorophenoxy)methyl)carbonyl-3-methyl-4-(4-fluorobenzyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)-5-methylpιperazιne, (2R)-1 -((4-chiorophenoxy)methyl)carbonyl-3-methyl-4-(4-fluorobenzyl)pιperazιne, (2S)-1-((4-chlorophenoxy)methyl)carbonyl-3-methyl-4-(4-fluorobenzyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3-(hydroxymethyl)pιperazιne, 4-(4-fluorobenzyl)-1 -((4-chlorophenoxy)methyl)carbonyl-3-(2-hydroxyethyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chiorophenoxy)methyl)carbonyl-2-(((methyl)ureιdo)methyl)pιperazιne, (2R,3R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,3-dιmethylpιperazιne (c/s)-1-((4-chlorophenoxy)methyl)carbonyl-3,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, 4-(4-fluorobeπzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-(((4-chlorophenoxy)- methyl)carbonyl)oxy)ethyl-5-methylpιperazιne, (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5- ((hydroxy)methyθpιperazιne; (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-((methoxy)- methyOpiperazme; (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1- methylethyOpiperazine; (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-5-(1- hydroxyethyOpiperaz e; (2R,5R)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyi-5-(1-hydroxyprop-3- enyl)pιperazine; (2R,5S)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)- 5-((cyano)methyl)piperazιne; (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((1 ,2,4-trιazol-2- yl)methyl)pιperazιne; (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5- ((tetrazolyl)methyθpιperazιne; (3S,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-3,5-dιmethylpιperazιne; 1-((4-chloro-3-nιtrophenoxy)methyi)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; (fraπs)-1-((4-chloro-2-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(diethyiamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-hydroxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((5-chloro-2-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((4-chloro-2-((ethyl)(1-methylbutyl)amιnomethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; 1-((4-chloro-2-amιnophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne; 1-((4-chloro-3-nitrophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyi)pιperazιne; (frans)-1-((4-chloro-2-(benzylamιno)phenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (f/-ans)-1-((4-chloro-2-((1-methylbutyl)amιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fiuorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-(/so-propylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(Λ/'-(2,4-dichlorophenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazine; (frans)-1-((4-chloro-2-(/V-(4-nιtrophenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; (frans)-1-((4-chloro-2-(Λ/'-(4-methylphenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((4-chloro-2-(Λ/'-benzylureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((cyclopropylmethyl)amιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl- 4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(phenylamιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (fraπs)-1-((4-chloro-2-(acetylamιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((methylamιno)(phenyl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(1-(phenyisulfonyl)(methyl)amιnoethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(1-(acetyl)(methyl)amιnoethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (trans)-! -((4-chloro-2-(1-(Λ/-methyl-Λ/'-ethylureιdo)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl- 4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(1-((methyl)(ethyl)amιno)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; (fraπs)-1-((4-chloro-2-(1-(dιmethylamιno)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e; (2R)-1-((4-chloro-2-((4-f-butoxycarbonylpιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2- methyl-4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-((pιperazιn-1-yi)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-(oxazol-2-yiamιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyi-4-(4- fluorobeπzyOpiperazine; 1-((4-chloro-2-(morpholιn-4-ylmethyl)phenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-bromo-2-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (fraπs)-1-((4-fluoro-3-chlorophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, 1-((4-chioro-2-methoxycarbonylphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (frat7s)-1-((4-chloro-2-methoxycarbonylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; 1-((4-chloro-2-amιnocarbonylphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-carboxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (frat?s)-1-((4-chloro-2-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (frans)-1-((4-chloro-2-cyanophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((3-cyanophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-methyl-2-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fiuorobenzyOpiperazine; (frans)-1-((3-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-methyl-2-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (fraπs)-1-((2-methoxycarbonylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((3-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπs)-1-((4-acetyl-2-(amιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((4-nitro-3-methylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, (trans)-! -((5-nιtro-2-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((4-amιno-3-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frat7s)-1-((5-nιtro-2-amιnophenoxy)methyl)carbonyl-2,5-dιmethyi-4-(4-fluorobenzyl)pιperazιne, (tra t7s)-1-((2-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (trans)-! -((3-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (ftaπs)-1-((4-methoxy-2-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((5-methoxy-2-acetylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((2-((2-hydroxyethyl)amιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((2-((2-hydroxyethoxy)carbonyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((2-(2-hydroxyethoxy)phenoxy)methyl)carboπyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((2-acetyl-4,5-dιmethylphenoxy)methyl)caroonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (ftat7s)-1-((5-methoxy-2-(methoxycarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyi-2-(/V'-methyiureιdo)- amιno)methyl)pιperazιne; (fraπs)-1-((4-methyl-2-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((3-chloro-5-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((2-methoxy-5-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((2-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((2-methylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazme; 1-((4-chlorophenoxy)methyl)carbonyl-2-(2-azιdoethyl)-4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(phthalιmido)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-(maleιmido)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobeπzyOpiperazme; (fraπs)-1-((4-chloro-2-((4-(benzylcarbonyl)pιperazιn-1-yl)methyl)phenoxy)methyl)-carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-((4-((2,3,4-tπfluorophenyl)amιnocarbonyl)pιperazιn-1- yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyi)pιperazιne, (fraπs)-1-((4-chloro-2-((4-((2-fluorophenyl)amιnocarbonyl)pιperazιn-1- yi)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-((Λ. -(2,6-difluorophenyl)ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(ethenylcarbonylamino)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(cyclopropylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chioro-2-(cyclopentylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((furan-2-yl)carbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(phenylcarbonylamιno)phenoxy)methyl)carboπyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((4-chloro-2-((Λ/'-(3-methoxyphenyl)ureιdo)phenoxy)methyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaz e, (fraπs)-1-((4-chloro-2-((Λ/'-(methoxycarbonylmethylcarbonyl)-Λ/- (methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((Λ/-(2-methoxycarbonylethyl)carbonyl-Λ/'- (methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((/V'-(3-methylbenzyl)amιnocarbonyl-Λ/'- (methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((/V-(3-trιfluoromethyl-4-fluorophenyl)carbonyl-Λ/- (methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-((Λ/'-(4-methyibenzyl)amιnocarbonyl-Λ/- (methyl)giycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fra/.s)-1-((4-chloro-2-((Λ/-(3-chiorophenyl)carbonyl-W- (methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((Λ/'-(4-fluorobenzyl)amιnocarbonyl-Λ/- (methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((4-chloro-2-(Λ/'-(2-ιodophenylcarbonyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(Λ/-(2,3-dιfluorophenylcarbonyl)glycιnamιdo)phenoxy)-methyl)carbonyl- 2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(/V'-((4-phenoxyphenyl)amιnocarbonyl)glycιnamιdo)phenoxy)- methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(Λf-(2,4-diflurophenylcarbonyl)glycιnamιdo)phenoxy)methyl)-carbonyl-2,5- dιmethyl-4-(4-fluorobenzyi)pιperazιne, (fraπs)-1-((4-chloro-2-((2-ιodophenylcarbonyl)amιnomethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-((ethoxycarbonylmethylcarbonyl)amιnomethyl)phenoxy)-methyl)carbonyl- 2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπs)-1-((4-chloro-2-(Λ/-(3-chloropropyl)ureιdomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl- 4-(4-fiuorobenzyl)pιperazιne; (fraπs)-1-((4-chloro-2-(Λ/-(2-fluoro-6-trifluoromethylphenyl)ureιdomethyl)phenoxy)- methyi)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-((3-fluorophenyl)carbonylamιnomethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (frans)-1-((4-chloro-2-(Λf-(2-(ethoxycarbony0ethyl)ureιdomethyl)phenoxy)-methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobeπzyl)pιperazιne; (2S)-1-((4-chloro-2-(ureιdo)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-((2 I 5-di(trifluoromethyl)phenyl)carbonylaminomethyl)- phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne; and (fra/7s)-1-((4-chloro-2-(A/'-(2-(phenyl)cyclopropyl)ureidomethy0phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne. 9 The compound of Claim 7 wherein. R 1a is one or more substituents independently selected from the group consisting of alkyl and hydroxyalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of halo, alkyl, alkoxy, formyl, nitro, cycioalkylaminoalkyl, hydroxyalkyl, ammo, aikylcarbonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonyialkylcarbonylamino, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, (alkylsulfonyθ(alkyl)amιnoalkyl, alkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarDonyl, (amιnoalkyl)amιnocarbonyl, hydroxyamidino, ureido, (haioalkylcarbonyl)ureιdo, ureidoalkyl, glycmamido, monoalkylglycmamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, alaninamido, and heterocyclylalkyl 10 The compound of Claim 9 selected from the group consisting of the following compounds: (frans)-1-((4-chloro-3-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chioro-2-(amιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (2R,5S)-1-((4-chloro-2-(amιnocarbonyi)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (2S,5R)-1-((4-bromo-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (2R,5S)-1-((3-hydroxy-5-methylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (2S,5R)-1-((4-nιtro-3-formylphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (2R)-1 -((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobeπzyl)pιperazιne, 4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2-(2-hydroxyethyl)pιperazιne, (frans)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,5-dιmethylpιperazιne, (2R,5S)-4-(4-fluorobenzyl)-1-((4-chlorophenoxy)methyl)carbonyl-2,5-dιmethylpιperazιne, (fraπs)-1-((4-chloro-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (2R,5S)-1-((4-chloro-3,5-dιmethoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (2R,5S)-4-(4-fiuorobenzyl)-1-((4-chiorophenoxy)methyl)carbonyl-2-(2-hydroxyethyl)- 5-methylpιperazιne, (2R,6R)-4-(4-fluorobenzyl)-1-((4-chloropheπoxy)methyl)carbonyl-2,6-dιmethylpιperazιne, (frans)-1-((4-chloro-2-methoxyphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; 1-((4-chloro-2-(hydroxymethyl)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (2R,5S)-1-((4-chloro-3-(hydroxymethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (fraπs)-1-((4-chloro-2-(1-hydroxyethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-(amιnomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((4-chloro-2-(ureιdomethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frat7s)-1-((4-chloro-2-amιnophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, 1-((4-chloro-2-(acetylamιno)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (frans)-4-(4-fluorobenzyl)-1-((2-acetylamιno-4-chlorophenoxy)methyl)carbonyl- 2,5-dιmethylpιperazιne, (frat7s)-1-((4-chloro-2-(propylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (frans)-1-((4-chloro-2-(methoxymethylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(2-(methoxycarbonyl)ethylcarbonylamιno)phenoxy)-methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frat7s)-1-((4-chloro-2-(2-(ethoxycarbonyl)ethylcarbonylammo)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(methylsulfonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (fraπs)-1-((4-chloro-2-(bromomethylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (2R)-1-((4-chloro-2-(glycιnamιdo)phenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazme, (frans)-1-((4-chloro-2-((Λ/'-methylgiycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (fraπs)-1-((4-chloro-2-(alanιnamιdo)phenoxy)methyl)carbonyl-2,5-αιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((4-chloro-2-((amιnocarbonyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (fraπs)-1-((4-chloro-2-((amιnocarbonyi)(methyl)glycιnamιdo)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frat7s)-1-((4-chloro-2-(A/'-ethyluredιo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((4-chloro-2-(ethylcarbonylamιno)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-amιno-5-nιtrophenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, dihydrochloride salt; (frans)-1-((4-chloro-2-(((ethyl)amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (ft-ans)-1-((4-chloro-2-(((dιethyl)amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-((4-chloro-2-(((cyciopropyl)amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobeπzyOpiperazine, (frat7s)-1-((4-chloro-2-(((dimethyl)amino)methyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-(((methyl)amιno)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((amιno)methyπphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((4-methylpιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne, (ftans)-1-((4-chloro-2-((pιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (frans)-1-((4-chloro-2-(ethylamιnomethyl)phenoxy)methyl)caroonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fra/7s)-1-((4-chloro-2-(1-(methylamιno)ethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(1-(methylsulfonyl)(methyl)amιnoethyl)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (2R)-1-((4-chloro-2-((pιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazine; (2R,5S)-1-((4-chloro-2-((piperazin-1-yl)methyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((4-f-butoxycarbonylpιperazιn-1-yl)methyl)phenoxy)methyl)carbonyl-2,5- dimethyl-4-(4-fluorobenzyl)piperazιne; (frans)-1-((4-chioro-2-(imidazol-1-ylmethyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(1-(imιdazol-1-yl)ethyl)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazme; (fraπs)-1 -((4-chloro-2-(tπazol-1 -ylmethyl )phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(tetrazol-1-ylmethyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((4-chloro-2-((morpholιn-4-yl)methyi)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (2R)-1-((4-chloro-2-amιnocarbonylphenoxy)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazine; 1-((4-chloro-2-formylphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)piperazιne; (2R,5S)-1-((4-chloro-2-formyiphenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (2R)-1-((4-chioro-2-formylphenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(methyiamιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-((4-chloro-2-((amιnocarbonylmethyl)amιnocarbonyl)phenoxy)methyl)carbonyl-2,5- dimethyl-4-(4-fluorobenzyl)pιperazιne; (frar.s)-1-((4-chloro-2-((2-amιnoethyl)amιnocarbonyθphenoxy)methyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)piperazine; (frans)-1-((4-chloro-2-((4-amιnocarbonylphenyl)amιnocarbonyl)phenoxy)methyl)carbonyl-2,5- dimethyl-4-(4-fluorobenzyl)piperazιne; (frans)-1-((4-chloro-2-(hydroxyamidino)phenoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-((4-chloro-2-acetylphenoxy)methyl)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)pιperazιne; (fraπs)-1-((2-(amιnocarbonyl)p enoxy)methyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-((Λ/'-(tπchloromethylcarbonyl)ureιdo)phenoxy)methyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(A -(methoxymethylcarbonyl)glycιnamιdo)phenoxy)methyl)-carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; and (fraπs)-1-((4-chloro-2-(Λ/ -(ethoxy carbonylammocarbonyl)- glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne 11 The compound of Claim 9 wherein R 2 is 4-fluoro and R 3 is phenyl substituted at the 4-posιtιon with chloro and at the 2-posιtιon by aminocarbonyl, ureido, or glycmamido, namely, the compound selected from the group consisting of the following compounds (2R,5S)-1-((4-chloro-2-(amιnocarbonyl)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-((4-chloro-2-(glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (2R)-1-((4-chloro-2-(ureιdo)phenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-((4-chloro-2-(ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (2R,5S)-1-((4-chloro-2-(ureιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; and (2R,5S)-1-((4-chloro-2-(glycιnamιdo)phenoxy)methyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine 12 The compound of Claim 3 wherein R 5 is methylene; R 7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl. 13. The compound of Claim 12 wherein: R 1a is one or more substituents independently selected from the group consisting of halo, alkyl, cycloalkyl, cycioalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, azidoalkyl, monoalkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyloxyalkyl, araikoxyalkylcarbonyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen and halo, R 3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, aminoalkoxy, cycloalkyl, cycioalkylaminoalkyl, aralkyl, hydroxyalkyl, (monoalkylamιno)araikyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (aikyicarbonyθ(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl alkoxycarbonylaminoalkyl, alkoxycarbonylalkyicarbonylaminoalkyl, (alkoxycarbonyθ(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyθ(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyθ(alkyl)amιnoalkyl, heterocyclylam oalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, dialkylaminocarbonylalkyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkyiureido, (monoalkyl)(monoaryl)ureido, (haioalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycinamido, monoalkylglycinamido, aminocarbonylglycmamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonyialkylcarbonyl)(alkyl)glycinamido, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycmamido, (arylcarbony (alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (monoarylamιnocarbonyi)g.ycιnamιdo, (monoarylamιnocarbonyθ(alkyl)glycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl 14 The compound of Claim 13 wherein R 1a is one or more substituents independently selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl, azidoalkyl, monoalkylureidoalkyl, aryioxyalkylcarbonyloxyalkyl, and heterocyclylalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro, R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, nitro, cyano, ammoalkoxy, cycioalkylaminoalkyl, hydroxyalkyl, (monoalkyiamιno)aralkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonyiamino, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyθ(alkyi)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, hydroxyamidino, ureido, monoalkylureido, monoaryiureido, monoaralkylureido, (monoalkyl)(monoaryl)ureιdo, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaraikylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycmamido, (arylcarbony (alkyl)glycιnamιdo, (monoaralkyiamιnocarbonyl)(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyl)(alkyl)glycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl 15 The compound of Claim 14 wherein R 1a is one or more substituents independently selected from the group consisting of alkyl and hydroxyalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of halo, alkyl, alkoxy, formyl, nitro, cycioalkylaminoalkyl, hydroxyalkyl, ammo, aikylcarbonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylammo, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyl, alkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, hydroxyamidino, ureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, alaninamido, and heterocyclylalkyl 16. The compound of Claim 15 wherein R 2 is 4-fluoro and R 3 is phenyl substituted at the 4-posιtιon with chloro and optionally substituted at the 2-posιtιon by aminocarbonyl, ureido, or glycmamido. 17. The compound of Claim 16 selected from the group consisting of the following compounds: (fraπs)-1-((4-chlorophenylamιno)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, 1-((4-chloro-2-(amιnocarbonyl)phenylamιno)methyl)carbonyl-2-methyl-4-(4- fluorobenzyOpiperazme; and 1-((4-chlorophenylamιno)methyl)carbonyl-2-methyl-4-(4-fluorobenzyi)pιperazιne. 18 The compound of Claim 3 wherein: R 4 is -C(R 8 ) 2 -, R 5 is methylene, each R 8 is independently selected from the group consisting of hydrogen, alkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonylammo, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylammo, alkylcarbonylammoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, heterocyclylcarbonyiaminoalkyl, arylsulfonylammo, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, ureidoalkyl, monoalkylureidoalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, and dialkylammoalkyl 19 The compound of Claim 18 wherein R 1a is one or more substituents independently selected from the group consisting of halo, alkyl, cycloalkyl, cycioalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, azidoaikyl, monoalkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyloxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen and halo; R 3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, aminoalkoxy, cycloalkyl, cycioalkylaminoalkyl, aralkyl, hydroxyalkyl, (monoalkylamιno)aralkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylammo, (alkylcarbonyθ(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιπoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, dialkylaminocarbonylalkyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, (monoalkyθ(monoaryl)ureιdo, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloaikyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycinamido, (arylcarbonyθ(alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (monoaryiamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyθ(alkyl)glycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl. 20. The compound of Cla'm 19 wherein. R 1a is one or more substituents independently selected from the group consisting of alkyl, cycloalkyl, hydroxyalkyl, hydroxyalkenyl, cyanoalkyl, alkoxyalkyl, monoalkylaminoalkyl, azidoalkyl, monoalkylureidoalkyl, aryloxyalkylcarbonyloxyalkyl, and heterocyclylalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of hydroxy, halo, alkyl, alkoxy, formyl, nitro, cyano, ammoalkoxy, cycioalkylaminoalkyl, hydroxyalkyl, (monoalkylamιno)aralkyl, alkoxyalkyl, am o, monoalkylamino, dialkyiamino, monoaralkylamino, aikylcarbonylammo, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylalkylcarbonylammoalkyl, alkylsulfonylammoalkyl, (alkylsulfony (alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsuifonyθ(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyl, aminocarbonyl, monoalkylammocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, hydroxyamidino, ureido, monoalkylureido, monoaryiureido, monoaralkylureido, (monoalkyl)(monoaryl)ureιdo, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbony (alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkyicarbonyl)glycιnamιdo, arylcarbonylgiycinamido, (arylcarbonyθ(alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyl)(alkyl)glycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl. 21. The compound of Cla>m 20 wherein: R 1a is one or more substituents independently selected from the group consisting of alkyl and hydroxyalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen, chloro or fluoro; R 3 is phenyl substituted by one or more substituents independently selected from the group consisting of halo, alkyl, alkoxy, formyl, nitro, cycioalkylaminoalkyl, hydroxyalkyl, amino, aikylcarbonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylsulfonylammo, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, (alkylsulfonyl)(alkyl)aminoalkyl, alkylcarbonyl, aminocarbonyl, monoalkyiaminocarbonyl, monoaryiaminocarbonyl, (aminocarbonylalkyl)aminocarbonyl, (aminoalkyl)aminocarbonyl, hydroxyamidino, ureido, (haloalkylcarbonyl)ureido, ureidoalkyl, glycinamido, monoalkylglycinamido, aminocarbonylglycinamido, (alkoxyalkylcarbonyl)glycinamido, (aminocarbonyl)(alkyl)glycinamido, (alkoxycarbonylaminoalkylcarbonyl)glycinamido, alaninamido, and heterocyclylalkyl. 22. The compound of Claim 21 wherein: R 2 is 4-fluoro; R 3 is phenyl substituted at the 4-position with chloro and optionally substituted at the 2-position by aminocarbonyl, ureido, or glycinamido; and one R 8 is hydrogen and the other R 8 is selected from the group consisting of amino, alkylcarbonylamino, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylamino, alkylcarbonylammoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, heterocyclyicarbonylaminoalkyl, arylsulfonylamino, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, ureidoalkyl, monoalkylureidoalkyl, monohaloalkylureidoalkyl, and aminoalkyl. 23. The compound of Claim 22 selected from the group consisting of the following compounds: (frans)-1-(2-(4-chlorophenyl)-3-(methylsulfonylamino)propyl)carbonyl-2,5-dimethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-(2-(4-chlorophenyl)-3-(acetylamιno)propyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-(2-(4-chlorophenyl)-2-(methylsulfonyiamιno)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-(2-(4-chlorophenyl)-2-(acetylamιno)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frans)-1-(2-(4-chlorophenyl)-2-(amino)ethyi)carbonyl-2,5-dimethyl-4-(4-fluorobenzyl)piperazine, (trans)-! -(2-(4-chlorophenyl)-2-(ureιdo)ethyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne, (frans)-1-(2-(4-chlorophenyl)-3-(ureιdo)propyi)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-(2-(4-chlorophenyl)-3-(amιπo)propyl)carDonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine, (frat7s)-1-(2-(4-chlorophenyl)-3-(f-butoxycarbonylamιπo)propyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme, (frans)-1-(2-(4-chlorophenyl)-2-((ethoxycarbonylmethylcarbonylamιno)ethyl)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne, (fraπs)-1-(2-(4-chlorophenyl)-2-(/V'-/so-propylureιdo)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-(2-(4-chlorophenyl)-2-(/V-(2-chloroethyl)ureιdo)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (fraπs)-1-(2-(4-chlorophenyl)-2-((2-nιtrophenyl)carbonylamιno)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperaziπe; (frat7s)-1-(2-(4-chlorophenyl)-2-((4-methoxyphenylmethyl)carbonylamιno)ethyi)carbonyl-2,5- dιmethyl-4-(4-fluorobenzyl)pιperazιne; (frans)-1-(2-(4-chlorophenyl)-2-((2,4-dιnιtrophenyl)sulfonylamιno)ethyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyi)pιperazιne; (fraπs)-1-(2-(4-chlorophenyl)-2-(cyclopropylcarbonylamιno)ethyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frans)-1-(2-(4-chlorophenyl)-2-((2-cyclopropylethyl)carbonylamιno)ethyl)carbonyl-2,5-dιmethyl- 4-(4-fluorobenzyl)pιperazιne; (frat7s)-1-(2-(4-chlorophenyl)-3-((2-methylpropyl)carbonylamιno)propyi)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne; (fraπs)-1-(2-(4-chlorophenyl)-3-(cycloppentylcarbonyiamιno)propyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazine; (frat7s)-1-(2-(4-chlorophenyO-3-(Λ/-(f-butyl)ureιdo)propyl)carbonyl-2,5-dιmethyl-4-(4- fluorobenzyOpiperazme; (frans)-1-(2-(4-chlorophenyl)-3-(A/-(ethyl)ureιdo)propyl)carbonyl-2,5-dιmethyl-4-(4- fiuorobenzyl)piperazine, (frat7s)-1-(2-(4-chlorophenyl)-3-(Λ/'-(3-choropropyl)ureιdo)propyl)carbonyl-2,5-dιmethyl-4-(4- fiuorobenzyOpiperazme; and (frans)-1-(2-(4-chlorophenyl)-3-((morDholιn-4-yl)carbonylamιno)propyl)carbonyl-2,5-dιmethyl-4- (4-fluorobenzyl)pιperazιne. 24. The compound of Claim 1 wherein R 3 is a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, am o, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, aikoxycarbonylalkyicarbonylamino, (alkylcarbonyl)(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, diaikylaminocarbonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido. 25. The compound of Claim 24 wherein: R 4 is -0-, -N(R 7 )- or -C(R 8 )-; R 5 is an alkylene chain; R 7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylammo, (alkylcarbonyl)(alkyl)amιno, aralkylcarbonyiamino, (aralkylcarbonyl)(alkyl)amino, alkylcarbonylammoalkyl, cycloalkylcarbonyiaminoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyi)amιnoalkyl, aralkylcarbonylaminoalkyl, heterocyclylcarbonylaminoalkyl, (aralkylcarbonyl)(alkyl)amιnoalkyl, arylsulfonytamino, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaioalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl 26. The compound of Claim 25 wherein: R 4 is -O-; R 5 is methylene; and R 6 is -C(O)-. 27. The compound of Claim 26 wherein: R 1a is one or more substituents independently selected from the group consisting of halo, alkyl, cycloalkyl, cycioalkylaminoalkyl, haloalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, alkoxyalkyl, aralkoxyalkyl, alkylthioalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, azidoalkyl, monoalkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyloxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and heterocyclylalkyl; and R 2 is one or more substituents independently selected from the group consisting of hydrogen and halo 28 The compound of Claim 27 wherein R 3 is selected from the group consisting of azepmyl, acπdinyl, benzimidazolyi, benzothiazolyl, benzoxazolyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl, carbazolyl, cmnolinyl, decahydroisoquinolyl, dioxolanyl, furyl, isothiazolyl, qumuclidinyl, imidazolyl, imidazolinyl, imidazolidinyl, isothiazolidmyl, indolyl, isomdolyl, indolmyl, isoindolmyl, mdanyl, indolizmyl, isoxazolyl, isoxazolidmyl, morpholmyl, naphthyπdinyl, oxadiazolyl, octahydroindolyl, octahydroisomdolyl, 2-oxopιperazιnyl, 2-oxopιperιdιnyl, 2-oxopyrroiιdιnyl, 2-oxoazepιnyl, oxazolyl, oxazolidmyl, pipeπdinyl, piperazmyl, 4-pιpeπdonyl, phenazmyl, phenothiaz yl, phenoxazmyl, phthalazmyl, pteπdinyl, puπnyl, pyrrolyl, pyrrolidmyl, pyrazolyl, pyrazolidmyl, pyπdinyl, pyrazmyl, pyπmidinyl, pyπdazinyi, quinazolmyl, qumoxalinyl, quinolmyl, qumuclidinyl, isoquinolmyl, thiazolyl, thiazolid yl, thiadiazolyl, tπazolyl, tetrazolyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, thiamorpholmyl, thiamorpholmyl sulfoxide, and thiamorpholmyl sulfone 29 The compound of Claim 28 wherein R 3 is benzopyranyl, benzopyranonyl, benzfuranyl, benzofuranonyl, quinolmyl, indolyl, indolmyl, oxazolyl, imidazolyl, or benzothienyl 30 The compound of Claim 29, namely, (frans)-1-((benzo[b]pyran-2-on-7- yloxy)methyl)carbonyl-2,5-dιmethyl-4-(4-fluorobenzyl)pιperazιne. 31 A pharmaceutical composition useful in treating an inflammatory disorder in a human in need of such treatment, which composition comprises a therapeutically effective amount of a compound of formula (la)- wherein R 1a is one or more substituents independently selected from the group consisting of oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycioalkylaminoalkyl, (cycloalkylalkyl)amιnoalkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, (alkoxy)aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyloxyalkyl, alkoxyalkylcarbonyloxyalkyl aralkoxyalkylcarbonyloxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloaikylalkyl)amιno, (cycloalkyalkyl)amιnoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkylcarbonyl)(alkyl)amιno, alkylcarbonylammoalkyl, (alkylcarbony (alkyl)amιnoaikyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιπo, alkoxycarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl, R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, ammoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloaikylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoaikylamιno)araikyl, (hydroxyalkyl)hιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyθ(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylammoalkyl, (alkoxycarbonyθ(alkyl)amιnoaikyl, alkylsulfonylammoalkyl, (alkylsulfonyθ(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyclylammoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (monoalkylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonyialkyl)amιnocarbonyi, (amιnoalkyl)amιnocarbonyl, (hydroxyaikyl)amιnocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, moπohaloalkylureido, (monoalkyθ(monoaryl)ureιdo, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycmamido, (arylcarbonyθ(alkyl)glycmamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)giycιnamιdo, (monoarylamιnocarbonyθ(alkyl)glycιnamιdo, glycmamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, or R 3 is a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyi, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl)(alkyl)amino, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylaminocarbonyiaikyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido, R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond, R 5 is an alkylene chain or an alkylidene chain, or, if R 4 is a bond, R 5 is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2 , R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond, each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl, and each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonylammo, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkyicarbonyθ(alkyl)amιno, aralkylcarbonylammo, (aralkylcarbonyθ(alkyi)amιno, alkylcarbonylammoalkyl, cycloalkyicarbonylaminoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoaikyl, aralkylcarbonylammoalkyl, heterocyclylcarbonyiaminoalkyl, (aralkylcarbonyl)(alkyl)amιnoalkyl, arylsulfonylammo, aikylsulfonylaminoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl; provided that when R 4 is -N(R 7 )-, R 3 can not be a heterocyclic ring system containing 4-8 members consisting of carbon atoms and only one nitrogen atom, and as a single stereoisomer or a mixture thereof; or a pharmaceufically acceptable salt thereof; and a pharmaceutically acceptable excipient. 32. A method of treating an inflammatory disorder in a human, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (la): wherein: R a is one or more substituents independently selected from the group consisting of oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycioalkylaminoalkyl, (cycloalkyialkyl)aminoalkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylaminoaikyl, (alkoxy)aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)aminoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarbonylalkyl)ureidoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, aryioxyalkylcarbonyloxyalkyl, alkoxyalkylcarbonyloxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno, (cycloalkyalkyl)amιnoaikyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkylcarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, (aikylcarbonyl)(alkyi)aminoalkyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycarbony (aikyl)amιnoaikyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl, R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, ammoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkylamιno)aralkyl, (hydroxyalkyl)fιιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylammo, (alkylcarbonyl)(alkyl)amino, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylammoalkyl, (alkoxycarbonyl)(alkyl)aminoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyθ(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyθ(alkyl)amιnoalkyl, heterocyclylaminoalkyi, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (monoalkylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonylalkyl)amιnocarbonyl, (amιnoalkyi)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyθ(monoaryl)ureιdo, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (aikoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycιnamιdo, (aikoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycinamido, (arylcarbony (alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyθ(alkyl)glycιnamιdo, glycmamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, or R 3 is a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyθ(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy. alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido, R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond, R 5 is an alkylene chain or an alkylidene chain, or, if R 4 is a bond, R 5 is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2 , R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond; each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonyiamino, (alkylcarbonyl)(alkyl)amιno, aralkylcarbonylamino, (aralkylcarbony (alkyl)amιno, alkylcarbonylammoalkyl, cycloalkyicarbonylaminoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, aralkylcarbonytaminoalkyl, heterocyclylcarbonylaminoalkyl, (aralkyicarbonyl)(alkyl)amιnoalkyl, arylsulfonylammo, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl, provided that when R 4 is -N(R 7 )-, R 3 can not be a heterocyclic ring system containing 4-8 members consisting of carbon atoms and only one nitrogen atom, and as a single stereoisomer or a mixture thereof, or a pharmaceufically acceptable salt thereof 33 A pharmaceutical composition useful in treating an inflammatory disorder in a human in need of such treatment, which composition comprises a therapeutically effective amount of a compound of formula (lb) wherein R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloaikylalkyl)amιno, (cycloalkyalkyl)amιnoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, am o, monoalkylamino, dialkylammo, monoaryiamino, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkyicarbonyl)(alkyl)amιno, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)aminoalkyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl, R 3 IS a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, ammoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkylamιno)aralkyl, (hydroxyalkyl)hιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, aikoxycarbonylalkylcarbonylamino, (alkylcarbonyθ(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylammoalkyl, (alkoxycarbonyθ(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyθ(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyclylammoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonyialkyl)amιnocarbonyl, (monoalkyiamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)ammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, moπohaloaikylureido, (monoaikyl)(monoaryl)ureido, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoaikyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycιπamιdo (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, aryicarbonylgiycinamido, (arylcarbonyθ(alkyl)glycιnamιdo, (monoaralkyiamιnocarboπyl)glycιnamιdo, (monoaralkyiamιnocarbonyθ(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyθ(aikyl)glycιnamιdo, giycinamidoaikyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonyiamino, (alkylcarbonyθ(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido; R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond; R 5 is an alkylene chain or an alkylidene chain, or, if R 4 is a bond, R 5 is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2 , R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond, each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl, and each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonyiamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkyicarbonylamino, (alkylcarbonyl)(alkyl)amιno, aralkylcarbonylamino, (aralkylcarbonyl)(alkyl)amino, alkylcarbonylammoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, aralkylcarbonylaminoalkyl, heterocyclylcarbonylaminoalkyl, (aralkylcarbonyl)(alkyl)amιnoalkyl, arylsulfonylamino, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl, provided that when R 4 is -N(R 7 )-, R 3 can not be a heterocyclic ring system containing 4-8 members consisting of carbon atoms and only one nitrogen atom, and as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 34 A method of treating an inflammatory disorder in a human, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a comDOund of formula (lb) wherein R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno, (cycloalkyalkyl)amιnoalkyi, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkylcarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)aminoalkyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycarbonyθ(alkyl)amιnoalkyi, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcaroonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl, R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, aminoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkyiamιno)aralkyl, (hydroxyalkyl)hιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyciylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonyialkylcarbonylamino (alkylcarbonyθ(alkyl)amιno, (alkoxycarboπyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonyiaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycioalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyθ(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyθ(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfony (alkyl)amιnoalkyl, heterocyclylammoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy )carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylaminocarbonyl, monoaralkylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (monoalkylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkyiureido, (monoalkyθ(monoaryl)ureιdo, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoaikyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkyicarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)giycιnamιdo, arylcarboπylglycmamido, (aryicarbonyθ(alkyl)giycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyθ(alkyl)glycιnamιdo, glycinamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl alkynyl, aryl, aralkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkyicarbonylamino, (alkylcarbonyθ(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylammocarbonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido; R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond; R 5 is an alkylene chain or an alkylidene chain, or, if R 4 is a bond, R 5 is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2 , R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond, each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, αialkylamino, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkyicarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonyiamino, (alkyicarbonyl)(alkyl)amιno, aralkylcarbonylammo, (aralkylcarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, cycloalkylcarbonylammoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, aralkylcarbonylammoalkyl, heterocyclylcarbonylammoalkyl, (aralkylcarbonyl)(alkyl)amιnoalkyl, arylsulfonylam o, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl, provided that when R 4 is -N(R 7 )-, R 3 can not be a heterocyclic ring system containing 4-8 members consisting of carbon atoms and only one nitrogen atom, and as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof 35. The method of Claim 34, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) wherein: R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, ammoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkyiamιno)aralkyl, (hydroxyalkyl)hιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyθ(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, (cycioalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylammoalkyl, (alkoxycarbonyl)(alkyl)aminoalkyl, alkylsulfonylammoalkyl, (alkylsulfony (alkyi)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyθ(alkyl)amιnoalkyl heterocyclyiaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (monoalkylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)ammocarbonyl, (alkoxycarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyθ(monoaryl)ureιdo, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloaikyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonyialkylcarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonyiamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycmamido, (arylcarbony (alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbony (alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoaryiamιnocarbonyl)(alkyl)glycιnamιdo, glycmamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl. 36. The method of Claim 35, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) wherein: R 4 is -0-, -N(R 7 )- or -C(R 8 )-, R 5 is an alkylene chain; R 7 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcaroonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; and each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl)(alkyl)amιno, aralkyicarbonylamino, (araikylcarbonyl)(alkyl)amino, alkylcaroonylammoalkyl, cycioalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, aralkylcarbonylammoalkyl, heterocyclylcarbonylaminoalkyl, (aralkylcarbonyl)(alkyl)amιnoalkyl, aryisulfonylammo, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl. 37. The method of Claim 36, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) wherein: R 4 is -0-; R 5 is methylene; and 38 The method of Claim 37. wnich method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) wherein: R 2 is one or more substituents independently selected from the group consisting of hydrogen and halo; R 3 is phenyl optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, ammoalkoxy, cycloalkyl, cycioalkylaminoalkyl, aralkyl, hydroxyalkyl, (monoalkylamιno)aralkyl, alkoxyalkyl, ammo, monoalkylamino. dialkylammo, monoaralkylamino, aikylcarbonylammo. alkenylcarbonylamino. cycloalkylcarbonylamino arylcarbonylamino, heterocyclylcarbonylammo, haloalkyicarDonylamino, alkoxyalkylcarbonylamino, aikoxycarbonylalkylcarbonylamino, (alkylcarbonyi)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonyiaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyaikyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyθ(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, alkylcarbonyl, (hydroxyalkoxy)carbonyl, aminocarbonyl, monoaikylaminocarbonyl, monoarylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocaroonyl, (hydroxyaikyl)amιnocarbonyl, dialkylaminocarDonylalkyl, hydroxyamidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, (monoalkyθ(monoaryl)ureιdo, (haloalkylcarDonyi)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haioalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (aikoxycarbonylaikyicarbonyl)(alkyl)glycinamido, (alkoxycarbonylamιnoalkylcarbonyi)giycιnamιdo, arylcarbonylglycinamido, (arylcarbony (alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyl)(alkyl)glycιnamιdo, (monoarylamιnocarbonyi)glycιnamιdo (monoarylamιnocarbonyl)(alkyl)glycιnamιdo, alaninamido, heterocyclyl and heterocyclylalkyl 39. The method of Claim 38, which method comprises administering to a human in need of such treatment a therapeutically effective amount of a compound of formula (lb) selected from the group consisting of the following compounds 1 -((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(benzyl)pιperazιne, 1-((3,5-dιmethoxypnenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; 1 -((2-(hydroxymethyl)phenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne 1-((4-ιodophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((2-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((4-methylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((2,4-dιchlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((4-bromo-2-chiorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((4-chloro-3-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; 1-((2-bromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; 1-((4-bromophenoxy)methyl)carbonyl-4-(benzyl)pιperazιne; 1-((2,4-dιbromophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; 1-((2-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; 1-((2-methoxy-5-nιtrophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((3,4,5-trιmethoxyphenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne, 1-((4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; 1-((4-chlorophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; 1-((3-fluoro-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne; 1-((3,5-dιmethoxy-4-chlorophenoxy)methyl)carbonyl-4-(4-chlorobenzyi)pιperazιne, 1-((4-bromo-2-formylphenoxy)methyl)carbonyl-4-(4-chlorobenzyl)pιperazιne, 1-((3-formyl-4-nιtrophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne; 1-((2-amιnocarbonyl-4-chlorophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne, 1-((3,5-dιmethoxy-4-bromophenoxy)methyl)carbonyl-4-(4-fluorobenzyl)pιperazιne, and 1 -((2-acetyiamιnophenoxy)methyl)carbonyl-4-(4-fluoroDeπzyl)pιperazιne 40 A compound of the following formula (lc) wherein Y is a pharmaceutically acceptable counteπon R 1 is one or more substituents independently selected from the grouo consisting of hydrogen oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycioalkylaminoalkyl, (cycloalkyialkyl)amιnoalkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkyicarbonylaminoalkyl, (aikoxy)aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)amιnoaikyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoatkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyloxyalkyl, alkoxyalkylcarbonyloxyalkyl, aralkoxyaikylcarbonyloxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxyjcycioalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno (cycloalkyalkyl)amιnoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (atkylcarboπyl)(alkyl)amιno, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)aminoalkyl, alkoxycarbonylamino, (alkoxycarboπyl)(alkyl)amιno alkoxycarbonylaminoalkyl, (alkoxycarDonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, aminocaroonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl; R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, aminoaikoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkylamιno)aralkyl, (hydroxyalkyl)hioaikyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)araikyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino. alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl)(alkyhamιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoaikyl, (cycloalkyalkyl)amιπoaikyl, alkoxycarbonylaminoalkyl, alkoxycarbonylaikyicarbonylaminoalkyl, (alkoxycarbonyO(alkyl)aminoaikyl, alkylsulfonylammoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsuifonyl)(alkyl)amιnoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyaikoxy)carbonyi, carboxyalkyl, alkoxycarDonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, ammocaroonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonylalkyi)amιnocarbonyl, (monoalkylamιπocarbonylalkyl)amιnocarbonyl, (carboxyaikyl)amιnocarbonyl, (alkoxycarbonylaikyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidino, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyθ(monoaryl)ureιdo, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoaikyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιπoalkylcarbonyl)glycιnamιdo, arylcarbonylglycinamido, (arylcarbonyθ(alkyl)gtycιnamιdo, (monoaralkylamιnocarbonyl)giycιnamιdo, (monoaralkylamιπocarbonyθ(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyl)(alkyl)glycιnamιdo, glycmamidoalkyl, alaninamido, monoalkylalaninamiαo, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, or R 3 is a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl alkynyl, aryl, aralkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarDonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyθ(alkyl)amιno, (alkoxycarbonyθ(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcaroonylammoalkyl, arylcarbonylaminoalkyl, (alkyicarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl aralkylcarbonyl, aminocarbonyl, monoalkylaminocaroonyi dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido, R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond, R 5 is an alkylene chain or an alkylidene chain, or, if R 4 is a bond, R 5 is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2 , R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond; each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl, each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarDonylalkylcarbonylamino, (alkylcarbonyl)(alkyl)amιno, aralkylcarbonylammo, (araikylcarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, (aikylcarbonyl)(alkyl)amιnoalkyl, aralkylcarbonylammoalkyl, heterocyclylcarbonylaminoalkyl, (aralkylcarbonyl)(alkyl)amιnoalkyl, arylsulfonylammo, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl; and R 9 is alkyl, aralkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkylcarbonylalkyl, alkylcarbonylammoalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, hetereocyclylalkyl, or cycloalkylalkyl; provided that when R 4 is -N(R 7 )-, R 3 can not be a heterocyclic ring system containing 4-8 members consisting of carbon atoms and only one nitrogen atom, and as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof 41. A pharmaceutical composition useful in treating an inflammatory disorder, which composition comprises a therapeutically effective amount of a compound of formula (lc): wherein: Y is a pharmaceufically acceptable counteπon: R 1 is one or more substituents independently selected from the group consisting of hydrogen, oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycioalkylaminoalkyl, (cycloalkylalkyl)amιnoalkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)araikyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, (alkoxy)aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkylcarbony (alkyl)amιnoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarDonylalkyl)ureιdoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, arvloxvalkylcaroonyloxyalkyl, alkoxyalkylcaroonyioxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, am ocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl mercapto mercaptoalkyl, alkylthio. alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno, (cycioalkyalkyl)amιnoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy )araikyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkylcarbonyl)(alkyl)amιno, alkylcarbonylammoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylaminocaroonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl; R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, ammoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkylamιno)aralkyl, (hydroxyalkyl)hιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιπo, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarboπyiamino, cycloalkylcarbonylamino. arylcarbonylamino. heterocyclylcaroonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycaroonylalkylcarbonylammo, (alkylcarbonyθ(aikyl)amιno, (aikoxycarbonyi)(alkyl)amιπo, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoaikyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, aikoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyθ(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (aryisulfonyl)(alkyl)amιnoalkyl, heterocyclylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylammocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (monoalkylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyl)(monoary!)ureιdo. dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycinamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιπocarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycιnamιdo, (alkoxycarDonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycmamido, (arylcarbonyl)(alkyl)glycιπamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (moπoaryiamιnocarbonyl)glycιnamιdo. (monoarylamιnocarbonyθ(alkyl)glycιnamιdo, glycmamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, aikoxycaroonylalkylcarbonylamino, (alkylcarbonyl)(aikyl)amino, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, aryicarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, ammocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido; R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond; R 5 is an alkylene chain or an alkylidene cnain, or, if R 4 is a bond, R 5 is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2 , R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond; each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarDonyl, each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, am o, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloaikylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylammo, (alkyicarbonyl)(alkyl)amιno, aralkylcarbonylamino, (aralkylcarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, cycloalkylcarooπylaminoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, aralkylcarbonylaminoalkyl, heterocyclyicarbonylaminoalkyl, (aralkylcarbony (alkyl)amιnoalkyl, arylsulfonylamino, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl; and R 9 is alkyl, aralkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkylcarbonylalkyl, alkylcarbonylammoalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, hetereocyclylalkyl, or cycloalkylalkyl; provided that when R 4 is -N(R 7 )-, R 3 can not be a heterocyclic ring system containing 4-8 members consisfing of carbon atoms and only one nitrogen atom, and as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof, and a pharmaceufically acceptable excipient 42. A method of treating an inflammatory disorder in a human, which method comprises administration to a human in need thereof of such treatment of a therapeutically effective amount of a compound of formula (lc). wherein Y is a pharmaceutically acceptable counteπon R 1b is one or more substituents independently selected from the group consisting of hydrogen, oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycioalkylaminoalkyl, (cycloalkylalkyl)amιnoalkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylammoalkyl, (alkoxy)aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl alkylsulfonylalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkylcarDonyi)(alkyl)amιnoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyioxyalkyl, alkoxyalkylcarbonyloxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno, (cycloalkyalkyl)amιnoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, am o, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hyαroxvalkylaminoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkylcarbonyl)(alkyl)amιno, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylamino, (alkoxycarbonyθ(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl, R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, aminoaikoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkytamιno)aralkyl, (hydroxyalkyl)hιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno. aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyciylcarbonylamino, haloalkylcarbonylamino. alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbony (alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarboπyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoaikyl, (alkoxycarbonyθ(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyl)(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)ammoalkyl, heterocyclyiaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (monoalkylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl monoaralkylammocarbonylalkyl, amidino, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyl)(monoaryl)ureιdo, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(aikyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycinamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyθ(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycιnamιdo, (alkoxycarboπyiamιnoalkylcarbonyl)glycιnamιdo, aryicarbonylglycinamido, (aryicarbonyl)(alkyl)glycinamido, (monoaralkyiamιnocarbonyl)glycιπamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (monoaryiamιnocarbonyl)glycιnamιdo, (monoaryiamιnocarbonyθ(aikyl)glycιnamιdo, glycinamidoalkyi, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, or R 3 is a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyθ(alkyl)amιno, (alkoxvcarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarDonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido, R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond, R 5 is an alkylene chain or an alkylidene chain, or, if R 4 is a bond, R 5 is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2 , R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond, each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl, each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloaikylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylammo, (alkylcarbonyl)(alkyl)amιno, aralkylcarbonylammo, (aralkylcarboπyθ(alkyl)amιno, alkylcarbonylammoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, aralkylcarbonylammoalkyl, heterocyclylcarbonylammoalkyl, (aralkylcarbonyl)(alkyl)amιnoalkyl, arylsuifonyiamino, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkyiaminocarDonylalkyl; and R 9 is alkyl, aralkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkylcarbonylalkyl, alkylcarbonylammoalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, hetereocyclylaikyl, or cycloalkylalkyl, provided that when R 4 is -N(R' )-, R 3 can not be a heterocyclic ring system containing 4-8 members consisting of carbon atoms and only one nitrogen atom, and as a single stereoisomer or a mixture thereof, or a pharmaceutically acceptable salt thereof 43 A compound of the following formula (Id)- wherein- R 1b is one or more substituents inαependently selected from the group consisting of hyαrogen, oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycioalkylaminoalkyl, (cycloalkylalkyl)amιnoalkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, (alkoxy)aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkylcarbonyl)(alkyi)aminoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, aryloxyalkyicarbonyloxyalkyl, alkoxyalkylcarbonyloxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno, (cycloalkyalkyl)amιnoalkyl, cyanoalkyl, alkenyl, alkyπyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkylcarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycaroonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyaikylcaroonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidino, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl; R 3 is a carbocylic ring system substituted by one or more substituents independenfiy selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, aminoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkylamιπo)aralkyl, (hydroxyaikyl)hioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylammo, haloalkylcaroonylamino. alkoxyalkylcarbonylamino, aikoxycarbonyialkylcarbonylamino, (alkylcarbonyl)(alkyl)amιno, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfony (alkyl)amιπoalkyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyciylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarDonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcaroonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonylalkyl)amιnocarbonyl, (monoalkylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyaikyl)amιnocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidino, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyl)(monoaryl)ureido, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyθ(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylalkylcarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycinamido, (arylcarbonyθ(alkyl)glycιnamιdo, (monoaralkylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyl)(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyl)(alkyl)glycιπamιdo, glycmamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, or R 3 is a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyθ(alkyl)amιno, (alkoxycarbonyθ(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbony!)(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido, R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond, R 5 is an alkylene chain or an alkylidene chain, or, if R 4 is a bond, R 5 is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2 , R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond; each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl, each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkyialkylcarbonylammo, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylammo, (alkylcarbonyl)(alkyl)amιno, aralkylcarbonylammo, (aralkylcarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, cycioalkylcarbonylaminoaikyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιπoalkyl, aralkylcarbonylaminoalkyl, heterocyclylcarbonylaminoalkyl, (aralkylcarboπyθ(alkyl)amιnoalkyl, arylsulfonylamino, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, monoalkvlaminocarbonylalkyl, and dialkylaminocarbonylalkyl, and R '° is a heterocyclyl optionally substituted by one or more substituents selected from the group consisting of hydroxy, mercapto, halo, alkyl, alkenyl, alkynyl, phenyl, phenylalkyl, phenylalkenyl, alkoxy, phenoxy, phenylalkoxy, haloalkyl, haloalkoxy, formyl, nitro, cyano amidino, cycloalkyl, hydroxyalkyl, alkoxyalkyl, phenoxyalkyi, phenyialkoxyaikyl, ammo, monoalkylamino, dialkylammo, monophenylamino, monophenylalkylamino, aminoalkyl monoalkylaminoalkyl, dialkylammoalkyl, monophenylaminoalkyl, monophenylalkylaminoalkyl, carboxy, alkoxycarbonyl, phenylcarbonyl, benzylcarbonyl, alkylcarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, phenylaminocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, ureido, monoalkylureido, monophenylureido, and monobenzylureido; provided that when R 4 is -N(R 7 )-, R 3 can not be a heterocyclic ring system containing 4-8 members consisting of carbon atoms and only one nitrogen atom, and as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof 44. The compound of Claim 43 wherein R 10 is a heterocyclyl selected from the group consisting of furanyl, thiophenyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, tπazolyl, thiadiazolyl, pyπdinyl, pyπdazinyl, pyπmidinyl, pyrazmyl, and tπazinyl. 45. A pharmaceutical composition useful in treating an inflammatory disorder in a human in need of such treatment, which composition comprises a therapeutically effective amount of a compound of formula (Id): wherein: R 1b is one or more substituents independently selected from the group consisting of hydrogen, oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycioalkylaminoalkyl, (cycloaikylalkyl)amιnoalkyl, haloalkyl, alkenyl, alkyπyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylalkyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylammoalkyl, (alkoxy)aralkyi, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcaroonyiaminoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyloxyalkyl, alkoxyalkylcarbonyloxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl; R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno, (cycloalkyalkyl)amιnoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)araikyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkylcaroonyl)(alkyl)amino, alkylcarbonylammoalkyl, (alkyicarbonyi)(alkyl)amιnoalkyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (aikoxycarbonyθ(aikyl)amιnoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl, R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, ammoalkoxy, cycioalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy )aralkyl, (monoalkylamιno)araikyl, (hydroxyalkyl)hioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, am o, monoalkylamino, dialkylamino, monoarylamino, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycioalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyθ(alkyl)amιno, (alkoxycarbonyθ(alkyl)amιno, alkylsulfonylammo, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonyiaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonylalkylcarbonylaminoalkyl, (alkoxycarbonyθ(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsulfonyθ(alkyl)amιnoaikyl, arylsulfonylammoalkyl, (arylsulfonyl)(alkyl)amιnoalkyl, heterocyclylammoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyaikoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, diaikyiamiπocarbonyioxyaikyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonylalkyl)ammocarboπyl, (monoalkylamιnocarbonylalkyl)amιnocarbonyl, (carboxyalkyl)amιnocarboπyl, (alkoxycarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyl)(monoaryl)ureido, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycmamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbonyl)(alkyl)glycιnamιdo, (aikoxycarbonylalkylcarbonyl)(alkyl)glycιnamιdo, (alkoxycarbonylamιnoalkylcarbonyl)glycιnamιdo, arylcarbonylglycinamido, (arylcarbonyθ(aikyl)giycιnamιdo, (monoaralkylammocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyθ(alkyl)giycιnamιdo, glycmamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, or R 3 is a heterocyclic πng system substituted by one or more subsfituents independently selected from the group consisfing of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl)(alkyl)amιno, (aikoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylammoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycmamido, R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond, R 5 is an alkylene chain or an alkylidene chain, or, if R 4 is a bond, R 5 is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2 , R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond, each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl; each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylamino, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonyialkylcarbonylamino, (alkylcarbonyl)(alkyl)amιno, aralkylcarbonylammo, (aralkylcarbonyl)(alkyi)amino, alkylcarbonylammoalkyl, cycloalkylcarbonylammoalkyl, alkoxycarbonylammoalkyl, (alkyicarbonyi)(aikyl)amιnoalkyl, aralkylcarbonyiaminoalkyl, heterocyclylcarbonylaminoalkyl, (aralkylcarbonyl)(alkyl)amιnoalkyl, arylsulfonylamino, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, am oalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl, and R 10 is a heterocyclyl optionally substituted by one or more substituents selected from the group consisting of hydroxy, mercapto, halo, alkyl, alkenyl, alkynyl, phenyl, phenylalkyl, phenylalkenyl, alkoxy, phenoxy, phenylalkoxy, haloalkyl, haloalkoxy, formyl, nitro, cyano, amidino, cycloalkyl, hydroxyalkyl, alkoxyalkyl, phenoxyalkyl, phenylalkoxyalkyl, am o, monoalkylamino, dialkylammo, monopnenylamino, monophenylalkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monophenylammoalkyl, monophenylalkylaminoalkyl, carboxy, alkoxycarbonyl, phenylcarbonyl, benzylcarbonyl, alkylcarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, phenylaminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, ureido, monoalkylureido, monophenylureido, and monobenzylureido; provided that when R 4 is -N(R 7 )-, R 3 can not be a heterocyclic ring system containing 4-8 members consisting of carbon atoms and only one nitrogen atom, and as a single stereoisomer or a mixture thereof, or a pharmaceufically acceptable salt thereof, and a pharmaceutically acceptable excipient 46. A method of treating an inflammatory disorder in a human, which method comprises adm isteπng to a human in need of such treatment a therapeufically effective amount of a compound of formula (Id): wherein: R 1 is one or more substituents independently selected from the group consisting of hydrogen, oxo, halo, alkyl, cycloalkyl, cycloalkylalkyl, cycioalkylaminoalkyl, (cycloalkylalkyl)amιnoaikyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, formyl, formylalkyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, (hydroxy)aralkyl, (hydroxy)cycloalkylaikyl, mercaptoalkyl, cyanoalkyl, haloalkylcarbonylaminoalkyl, (aikoxy)aralkyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkylthioalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, (alkylcarbonyθ(alkyl)amιnoalkyl, azidoalkyl, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, alkoxycarbonylaminoalkyl, hydroxyalkylammoalkyl, aryloxyalkylcarbonyloxyalkyl, alkoxyalkylcarbonyloxyalkyl, aralkoxyalkylcarbonyloxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, aralkylcarbonyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, arylsulfonyl, heterocyclyl and heterocyclylalkyl, R 2 is one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, (cycloalkylalkyl)amιno, (cycloalkyaikyl)amιnoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy )aralkyl, hydroxyalkylthioalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, ammo, monoalkylamino, dialkylamino, monoarylammo, monoaralkylamino, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, aikylcarbonylammo, (alkylcarbony (alkyi)amιno, alkylcarbonylammoalkyl, (alkyicarbonyθ(alkyl)amιnoaikyl, alkoxycarbonylamino, (alkoxycarbonyl)(alkyl)amιno, alkoxycarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, alkylcarbonylalkyl, arylcarbonyl, arylcarbonylaikyl, aralkylcarbonyl, aralkylcarbonylalkyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoaryiaminocarbonyl, monoaralkylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidino, guanidino, ureido, monoalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, heterocyclyl and heterocyclylalkyl; R 3 is a carbocylic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, hydroxysulfonyl, halo, alkyl, mercapto, mercaptoalkyl, alkylthio, alkylsulfinyl, alkylsufonyl, arylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkoxy, hydroxyalkoxy, aryloxy, haloalkyl, formyl, formylalkyl, nitro, nitroso, cyano, aralkoxy, haloalkoxy, aminoalkoxy, cycloalkyl, cycloalkylalkyl, (hydroxy)cycloalkylalkyl, cycloalkylammo, cycioalkylaminoalkyl, cyanoalkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, hydroxyalkyl, (hydroxy)aralkyl, (monoalkylamιπo)aralkyl, (hydroxyalkyl)hιoalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkyl, (alkoxy)aralkyl, aryloxyalkyl, aralkoxyalkyl, am o, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aminoalkylamino, heterocyclylamino, (cycloalkylalkyl)amιno, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylammo, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylammo, (alkylcarbonyl)(alkyl)amino, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, ammoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, hydroxyalkylammoalkyl, monoarylaminoalkyl, monoaraikylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarboπyl)(alkyl)amιnoalkyl, (cycloalkyalkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, alkoxycarbonyialkylcarbonylaminoalkyl, (alkoxycarbonyl)(alkyl)amιnoalkyl, alkylsulfonylammoalkyl, (alkylsuifonyl)(alkyl)amιnoalkyl, arylsulfonylammoalkyl, (arylsulfony (alkyl)amιnoalkyl, heterocyclyiaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, (hydroxyalkoxy)carbonyl, carboxyalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, alkoxyalkylcarbonyloxyalkyl, dialkylaminocarbonyloxyalkyl, alkylcarbonylalkyl, arylcarbonylaikyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, monoaralkylammocarbonyl, (amιnocarbonyialkyl)amιnocarbonyl, (monoalkylamιnocarbonylaikyl)amιnocarbonyl, (carboxyalkyl)amιnocarbonyl, (alkoxycarbonylalkyl)amιnocarbonyl, (amιnoalkyl)amιnocarbonyl, (hydroxyalkyl)amιnocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, monoaralkylammocarbonylalkyl, amidmo, hydroxyamidino, guanidino, ureido, monoalkylureido, monoarylureido, monoaralkylureido, monohaloalkylureido, (monoalkyθ(monoaryl)ureιdo, dialkylureido, diarylureido, (haloalkylcarbonyl)ureιdo, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monoarylureidoalkyl, monoaralkylureidoalkyl, monohaloalkylureidoalkyl, (haloalkyl)(alkyl)ureιdoalkyl, (alkoxycarbonylalkyl)ureιdoalkyl, glycinamido, monoalkylglycinamido, ammocarbonylglycinamido, (alkoxyalkylcarbonyl)glycιnamιdo, (amιnocarbony (alkyi)glycιπamιdo, (alkoxycarbonylalkylcarbonyl)(alkyi)glycιnamιdo, (alkoxycarbonyiamιnoalkylcarbonyl)giycιnamιdo, arylcarbonylgiycinamido, (arylcarbonyθ(alkyl)glycιnamιdo, (monoaraikylamιnocarbonyl)glycιnamιdo, (monoaralkylamιnocarbonyθ(alkyl)glycιnamιdo, (monoarylamιnocarbonyl)glycιnamιdo, (monoarylamιnocarbonyθ(alkyl)glycmamιdo, glycinamidoalkyl, alaninamido, monoalkylalaninamido, alanmamidoalkyl, heterocyclyl and heterocyclylalkyl, a heterocyclic ring system substituted by one or more substituents independently selected from the group consisting of hydrogen, hydroxy, halo, alkyl, alkylsufonyl, arylsulfonyl, alkoxy, hydroxyalkoxy, haloalkyl, formyl, nitro, cyano, haloalkoxy, alkenyl, alkynyl, aryl, aralkyl, am o, monoalkylamino, dialkylammo, monoarylammo, monoaralkylamino, aikylcarbonylammo, alkoxycarbonylamino, alkenylcarbonylamino, cycloalkylcarbonylamino, arylcarbonylamino, haloalkylcarbonylamino, alkoxyalkylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkyicarbonyi)(alkyl)amino, (alkoxycarbonyl)(alkyl)amιno, alkylsulfonylammo, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, alkylcarbonylammoalkyl, arylcarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, alkoxycarbonylaminoalkyl, carboxy, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, ammocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, monoarylammocarbonyl, ammocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, monoarylammocarbonylalkyl, guanidino, ureido, monoalkylureido, ureidoalkyl, monoalkylureidoalkyl, and glycinamido; R 4 is -0-, -N(R 7 )-, -C(R 8 ) 2 - or a bond; R 5 is an alkylene chain or an alkylidene chain, or, if R 4 is a bond, R 5 is an alkylidene chain optionally substituted by aryl or -N(R 7 ) 2> R 6 is -C(O)-, -C(S)-, -CH 2 - or a bond; each R 7 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, alkylcarbonyl, alkylcarbonylalkyl, aralkylcarbonyl, aralkylcarbonylalkyl, aminocarbonyl, monoalkylammocarbonyl, dialkylaminocarbonyl, and alkoxycarbonyl, each R 8 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, hydroxy, alkoxy, hydroxyalkyl, alkoxyalkyl, ammo, monoalkylamino, dialkylammo, aikylcarbonylammo, cycloalkylcarbonylamino, cycloalkylalkylcarbonyiamino, alkoxycarbonylamino, alkylsulfonylammo, arylcarbonylamino, alkoxycarbonylalkylcarbonylamino, (alkylcarbonyl)(alkyi)amιno, aralkylcarbonylamino, (aralkylcarbonyθ(alkyl)amιno, alkylcarbonylammoalkyl, cycloalkylcarbonylaminoalkyl, alkoxycarbonylaminoalkyl, (alkylcarbonyl)(alkyl)amιnoalkyl, aralkylcarbonylaminoalkyl, heterocyclylcarbonylaminoalkyl, (aralkylcarbonyθ(alkyl)amιnoalkyl, arylsuifonylamino, alkylsulfonylammoalkyl, ureido, monoalkylureido, monohaloalkylureido, dialkylureido, ureidoalkyl, monoalkylureidoalkyl, dialkylureidoalkyl, monohaloalkylureidoalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, and dialkylaminocarbonylalkyl, and R 10 is a heterocyclyl optionally substituted by one or more substituents selected from the group consisting of hydroxy, mercapto, halo, alkyl, alkenyl, alkynyl, phenyl, phenylalkyl, phenylalkenyl, alkoxy, phenoxy, phenylalkoxy, haloalkyl, haloalkoxy, formyl, nitro, cyano, amidino, cycloalkyl, hydroxyalkyl, alkoxyalkyl, phenoxyalkyl, phenylalkoxyalkyl, ammo, monoalkylamino, dialkylamino, monophenylamino, monophenylalkylamino, aminoalkyl, monoalkylaminoalkyl, dialkylammoalkyl, monophenylaminoalkyl, monophenylalkylaminoalkyl, carboxy, alkoxycarbonyl, phenylcarbonyl, benzylcarbonyl, alkylcarbonyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, phenylaminocarbonyl, aminocarbonylalkyl, monoalkylaminocarbonylalkyl, dialkylaminocarbonylalkyl, ureido, monoalkylureido, monophenylureido, and monobenzyiureido; provided that when R 4 is -N(R 7 )-, R 3 can not be a heterocyclic ring system containing 4-8 members consisting of carbon atoms and only one nitrogen atom, and as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof.

Inventors: BAUMAN JOHN G, BUCKMAN BRAD O, GHANNAM AMEEN F, HESSELGESSER JOSEPH E, HORUK RICHARD, ISLAM IMADUL, LIANG MEINA, MAY KAREN B, MONAHAN SEAN D, MORISSEY MICHAEL M, NG HOWARD P, WEI GUO PING, XU WEI, ZHENG WEI, BAUMAN, JOHN, G., BUCKMAN, BRAD, O., GHANNAM, AMEEN, F., HESSELGESSER, JOSEPH, E., HORUK, RICHARD, ISLAM, IMADUL, LIANG, MEINA, MAY, KAREN, B., MONAHAN, SEAN, D., MORISSEY, MICHAEL, M., NG, HOWARD, P., WEI, GUO, PING, XU, WEI, ZHENG, WEI
Applicants: SCHERING AG, SCHERING AKTIENGESELLSCHAFT
Application year: 1998
Main classification: C07D241
IPC codes: A61K31, A61P29, A61P43, C07D241, C07D261, C07D295, C07D307, C07D401, C07D403, C07D405, C07D409, C07D413