NOVEL COMPOUNDS AND COMPOSITIONS AS CATHEPSIN INHIBITORS

Abstract: The present invention relates to novel selective cathepsin S inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making

Description: NOVEL COMPOUNDS AND COMPOSITIONS AS CATHEPSIN INHIBITORS THE INVENTION This application is based on and claims priority from U.S . Provisional Application S.N. 60/257,603 filed on December 22, 2000. This Application relates to compounds and compositions for treating diseases associated with cysteine protease activity, particularly diseases associated with activity of cathepsin S. DESCRIPTION OF THE FIELD Cysteine proteases represent a class of peptidases characterized by the presence of a cysteine residue in the catalytic site of the enzyme. Cysteine proteases are associated with the normal degradation and processing of proteins. The aberrant activity of cysteine proteases, e.g., as a result of increase expression or enhanced activation, however, may have pathological consequences, h this regard, certain cysteine proteases are associated with a number of disease states, including arthritis, muscular dystrophy, inflammation, tumor invasion, glomerulonephritis, malaria, periodontal disease, metachromatic leukodystrophy and others . An increase in cathepsin S activity contributes to the pathology and/or symptomatology of a number of diseases. Accordingly, molecules that inhibit the activity of cathepsin S protease are useful as therapeutic agents in the treatment of such diseases. SUMMARY OF THE INVENTION This Application relates to compounds of Formula I: I X 1 is -C(B )φ?)X 2 or -X 3 ; X 2 is cyano, -CHO, -C(R 7 )(R 8 )R 5 , -C(R 7 )(R 8 )CF 3 , -C(R 7 )(R 8 )CF 2 CF 2 R 9 -CH=CHS(O) 2 R 5 , -C(R 7 )(R 8 )CF 2 C(O)NR 5 R 6 , -C(R 7 )(R 8 )C(R 7 )(R 8 )NR 5 R 6 , -C(R 7 )(R 8 )C(R 7 )(R 8 )OR 5 , -C(R 7 )(R 8 )CH 2 OR 5 , -C(R 7 )(R 8 )CH 2 N(R 6 )SO 2 R 5 , -C(R 7 )(R 8 )C(R 7 )(R 8 )N(R 6 )(CH 2 ) 2 OR 6 , -C(R 7 )(R 8 )C(R 7 )(R 8 )N(R 6 )(CH 2 ) 2 NR 6 or -C(R 7 )(R 8 )C(R 7 )(R 8 )R 5 ; wherein R 5 is (C M )alkyl, (C 6 . 10 )aryl(Co- 6 )alkyl, hetero(C _ιo)aryl(Co- 6 )alkyl, (C 4 . 10 )cycloalkyl(C 0 - 6 )alkyl or hetero(C 4 .ιo)cycloalkyl(C 0 - 6 )alkyl; R 6 is hydrogen or (Cι. 6 )alkyl; R 7 is hydrogen or (Cι. )alkyl and R 8 is hydroxy or R 7 and R 8 together form oxo; R 9 is hydrogen, halo, (Cι_ 4 )alkyl, (C 5 -ι 0 )aryl(Co. 6 )alkyl or hetero(C 5 . 10 )aryl(Co. 6 )alkyl; X 3 represents a group of Formula (a): (a) in which n is 1 or 2, z is 0 or 1, X 5 is selected from NR 10 , S or O, wherein R 10 is hydrogen or (Cι. 6 )alkyl, and X 6 is O, S or NR π , wherein R 11 is selected from hydrogen, (Cι. 6 )alkyl, -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 S(O) 2 R 14 , -R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 C(O)NR 12 R 15 and -X 4 S(O) 2 NR 12 R 15 , in which X 4 is a bond or (Cι_ 6 )alkylene; R 12 at each occurrence independently is hydrogen or (Cι. 6 )alkyl; R 13 is hydrogen, (Cι. 6 )alkyl or halo-substituted(C 1 . 6 )alkyl, R 14 is ( ^alkyl or halo-substituted(Cι- 6 )alkyl and R 15 is (C 3 .ι 0 )cycloaIkyl(C 0 - 6 )alkyl, hetero(C 3 . 10 )cycloalkyl(C 0 . 3 )alkyl, (C 6 . 10 )aryl(Co- 6 )alkyl, hetero(C 5 .ιo)aryl(C 0 - 6 )alkyl, (C 9 .ι 2 )bicycloaryl(Co- 6 )alkyl or hetero(C 8 .ι 2 )bicycloaryl(Co- 6 )alkyl; wherein within X 1 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical R 20 selected from -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR 15 R 12 , -X 4 S(O) 2 NR 15 R 12 , -X 4 NR 12 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 ; and wherein X 1 and R 20 may be substituted further with 1 to 5 radicals independently selected from (Cι_ 6 )alkyl, cyano, halo, halo-substituted(Cι_ 4 )alkyl, nitro, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 wherein X 4 , R 12 , R 13 , R 14 and R 15 are as defined above; R 1 and R 2 are both fluoro; or R 1 is hydrogen or (Cμ^alkyl and R 2 is selected from the group consisting of hydrogen, (Cι. 6 )alkyl, cyano, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 1 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 , -X 4 S(O) 2 R 14 , -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR 15 R 12 , -X 4 S(O) 2 NR 15 R 12 , -X 4 NR 12 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 , wherein X 4 , R 12 , R 13 , R 14 and R 15 are as defined above; or R 1 and R 2 taken together with the carbon atom to which both R and R ~ are attached form (C 3 . 8 )cycloalkylene or hetero(C 3 . 8 )cycloalkylene; wherein R 2 , said cycloalkylene and said heterocycloalkylene may be substituted further with 1 to 3 radicals independently selected from (Cι„ 6 )alkyl, cyano, halo, halo-substitated(C M )alkyl, nitro, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X OC(O)R 13 , -X C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 , wherem X 4 , R 12 , R 13 and R 14 are as defined above; R 3 and R 4 are independently -C(R 16 )(R 17 )X 7 , wherein R 1( > and R 17 are hydrogen, (Cι. 6 )alkyl or fluoro, or R 16 is hydrogen and R 17 is hydroxy and X 7 is selected from -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 , -X 4 S(O) 2 R 14 , -R 15 , -X OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR ls , -X 4 C(O)NR 15 R 12 , -X 4 S(O) 2 NR 15 R 12 , -X 4 NR 12 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 , wherein X 4 , R 12 , R 13 , R 14 and R 15 are as defined above; wherein within one of R 3 or R 4 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical R 21 selected from -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR 12 R 15 , -X 4 S(O) 2 NR 15 R 12 , -X 4 NR 12 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 , wherein X 4 , R 12 and R 15 are as defined above; and wherein each of R 3 , R 4 and R 21 may be substituted further with 1 to 5 radicals independently selected from (Cι. 6 )alkyl, cyano, halo, halo-substituted(Cι. 4 )alkyl, nitro, -X 4 NR 1 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 , wherem X 4 , R 12 , R 13 and R 14 are as defined above; provided that only one bicyclic ring structure is present within each of R 3 or R 4 ; and provided that when X 2 is cyano and X 7 within one of R 3 or R 4 is -X 4 C(O)R 13 or -X 4 C(O)R 15 , wherein X 4 is a bond, then X 7 within the other of R 3 or R 4 is limited to -X 4 SR 15 , -X 4 S(O)R 15 and -X 4 S(O) 2 R 15 , wherein R 15 is (C 6 -ιo)aryl(C 1 . 6 )alkyl substituted with 1 to 5 radicals or hetero(C 5 . 10 )aryl(Co- 6 )aιkyl optionally substituted with 1 to 5 radicals, wherem said radicals are independently selected from (Cι_ 6 )alkyl, cyano, halo, halo-substituted(Cι. 4 )alkyl, nitro, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 1 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 1 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 , wherein X 4 , R 12 , R 13 and R 14 are as defined above, provided that the radical is not selected from only halo when R 15 is (C 6 -ιo)aryl(Cι. 6 )alkyl; and provided that when X 2 is cyano then X 7 within R 3 and R 4 is not -X 4 C(O)NR 12 R 12 , -X 4 C(O)NR 15 R 12 or -X 4 C(O)NR 18 R 19 , wherein X 4 is a bond and R 18 and R 19 together with the nitrogen atom to which they are attached form hetero(C 3 _ιo)cycloalkyl or hetero(C 5 . 10 )aryl; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. A second aspect of the mvention is a pharmaceutical composition which contains a compound of Formula I or a N-oxide derivative, individual isomer or mixture of isomers thereof, or a pharmaceutically acceptable salt thereof, in admixture with one or more suitable excipients. A third aspect of the invention is a method for treating a disease in an animal in which inhibition of cathepsin S can prevent, inhibit or ameliorate the pathology and/or symptomatology of the disease, which method comprises administering to the animal a therapeutically effective amount of compound of Formula I or a N-oxide derivative, individual isomer or mixture of isomers thereof; or a pharmaceutically acceptable salt thereof. A fourth aspect of the invention is the processes for preparing compounds of Formula I and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts thereof. DETAILED DESCRIPTION OF THE INVENTION DETAILED DESCRIPTION OF THE INVENTION Definitions: Unless otherwise stated, the following terms used in the specification and claims are defined for the purposes of this Application and have the following meanings. "Alicyclic" means a moiety characterized by arrangement of the carbon atoms in closed non-aromatic ring structures having properties resembling those of aliphatics and may be saturated or partially unsaturated with two or more double or triple bonds. "Aliphatic" means a moiety characterized by a straight or branched chain arrangement of the constituent carbon atoms and may be saturated or partially unsaturated with two or more double or triple bonds. "Alkyl" represented by itself means a straight or branched, saturated or unsaturated, aliphatic radical having the number of carbon atoms indicated (e.g., (Cι. 6 )alkyl includes methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methylallyl, ethynyl, 1-propynyl, 2-propynyl, and the like). Alkyl represented along with another radical (e.g., as in arylalkyl) means a straight or branched, saturated or unsaturated aliphatic divalent radical having the number of atoms indicated or when no atoms are indicated means a bond (e.g., (C 6 -ιo)aryl(Co- 3 )alkyl includes phenyl, benzyl, phenethyl, 1-phenylethyl 3-phenylpropyl, and the like). "Alkylene", unless indicated otherwise, means a straight or branched, saturated or unsaturated, aliphatic, divalent radical having the number of carbon atoms indicated (e.g., (Ci_ 6 )alkylene includes methylene (-CH 2 -), ethylene (-CH 2 CH 2 -), trimethylene (-CH 2 CH 2 CH 2 -), tetramethylene (-CH 2 CH 2 CH 2 CH 2 -) 2-butenylene (-CH 2 CH=CHCH 2 -), 2-methyltetramethylene (-CH 2 CH(CH 3 )CH 2 CH 2 -), pentamethylene (-CH 2 CH 2 CH 2 CH 2 CH 2 -) and the like). "Alkylidene" means a straight or branched saturated or unsaturated, aliphatic, divalent radical having the number of carbon atoms indicated (e.g. (Cι_ 6 )alkylidene includes methylene (=CH 2 ), ethylidene (=CHCH 3 ), isopropylidene (=C(CH 3 ) 2 ), propylidene (=CHCH 2 CH 3 ), allylidene (=CH ~ CH=CH 2 ), and the like). "Amino" means the radical -NH 2 . Unless indicated otherwise, the compounds of the invention containing amino moieties include protected derivatives thereof. Suitable protecting groups for amino moieties include acetyl, tert-butoxycarbonyl, benzyloxycarbonyl, and the like. "Animal" includes humans, non-human mammals (e.g., dogs, cats, rabbits, cattle, horses, sheep, goats, swine, deer, and the like) and non-mammals (e.g., birds, and the like). "Aromatic" means a moiety wherem the constituent atoms make up an unsaturated ring system, all atoms in the ring system are sp" hybridized and the total number of pi electrons is equal to 4n+2. "Aryl" means a monocyclic or fused bicyclic ring assembly containing the total number of ring carbon atoms indicated, wherein each ring is comprised of 6 ring carbon atoms and is aromatic or when fused with a second ring forms an aromatic ring assembly. For example, optionally substituted (C 6 -i 0 )aryl as used in this Application includes, but is not limited to, biphenyl-2-yl, 2-bromophenyl, 2-bromocarbonylphenyl, 2-bromo- 5-fluorophenyl, 4-tert-butylphenyl, 4-carbamoylphenyl, 4-carboxy-2-nitrophenyl, 2-chlorophenyl, 4-chlorophenyl, 3-chlorocarbonylphenyl, 4-chlorocarbonylphenyl, 2-chloro-4-fluorophenyl, 2-chloro-6-fTuorophenyl, 4-chloro-2-nitrophenyl, 6-chloro- 2-nitrophenyl, 2,6-dibromophenyl, 2,3-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2-difluoromethoxyphenyl, 3,5-dimethylphenyl, 2-ethoxycarbonylphenyl, 2-fluorophenyl, 2-iodophenyl, 4-isopropylphenyl, 2-methoxyphenyl, 4-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 5-methyl-2-nitrophenyl, 4-methylsulfonylphenyl, naphth-2-yl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2,3,4,5,6-pentafluorophenyl, phenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluorometliylphenyl, 2-trifluoromethylsulfanylphenyl, 4-trifluoromethylsulfanylphenyl, and the like. "Bicycloaryl" means a bicyclic ring assembly containing the number of ring carbon atoms indicated, wherein the rings are linked by a single bond or fused and at least one of the rings comprising the assembly is aromatic, and any (Cι. 6 )alkylidene, carbocyclic ketone, thioketone or iminoketone derivative thereof (e.g., (C 9 .ι 2 )bicycloaryl includes biphenyl, cyclohexylphenyl, 1,2-dihydronaphthyl, 2,4-dioxo-l,2,3,4-tetrahydronaphthyl, indanyl, indenyl, 1,2,3,4-tetrahydronaphthyl, and the like). "Carbamoyl" means the radical -C(O)NH 2 . Unless indicated otherwise, the compounds of the invention containing carbamoyl moieties include protected derivatives thereof. Suitable protecting groups for carbamoyl moieties include acetyl, tert-butoxycarbonyl, benzyloxycarbonyl, and the like and both the unprotected and protected derivatives fall within the scope of the invention. "Carbocyclic ketone derivative" means a derivative containing the moiety -C(O)-. "Carboxy" means the radical -C(O)OH. Unless indicated otherwise, the compounds of the invention containing carboxy moieties include protected derivatives thereof. Suitable protecting groups for carboxy moieties include benzyl, tert-butyl, and the like. "Cycloalkyl" means a saturated or partially unsaturated, monocyclic, fused bicyclic or bridged polycyclic ring assembly containing the number of ring carbon atoms indicated, and any (Cι_ 6 )alkylidene, carbocyclic ketone, thioketone or iminoketone derivative thereof (e.g., (C 3 _ιo)cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, 2,5-cyclohexadienyl, bicyclo[2.2.2]octyl, adamantan-1-yl, decahydronaphthyl, oxocyclohexyl, dioxocyclohexyl, thiocyclohexyl, 2-oxobicyclo[2.2.1]hept-l-yl, and the like). "Cycloalkylene" means a divalent saturated or partially unsaturated, monocyclic ring or bridged polycyclic ring assembly containing the number of ring carbon atoms indicated, and any carbocyclic ketone, thioketone or iminoketone derivative thereof. For example, the instance wherein "R 1 and R 2 together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene" includes, but is not limited to, the following: "Disease" specifically includes any unhealthy condition of an animal or part thereof and includes an unhealthy condition that may be caused by, or incident to, medical or veterinary therapy applied to that animal, i.e., the "side effects" of such therapy. "Halo" means fluoro, chloro, bromo or iodo. "Halo-substituted alkyl", as an isolated group or part of a larger group, means ' "alkyl" substituted by one or more "halo" atoms, as such terms are defined in this Application. Halo-substituted alkyl includes haloalkyl, dihaloalkyl, trihaloalkyl, perhaloalkyl and the like (e.g. halo-substituted (Cι. 3 )alkyl includes chloromethyl, dichloromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, perfluoroethyl, 2,2,2-trifluoro-l,l-dichloroethyl, and the like). "Heteroatom moiety" includes -N=, -NR-, -O-, -S- or -S(O) 2 -, wherein R is hydrogen, (Cι_6)alkyl or a protecting group. "Heterocycloalkylene" means cycloalkylene, as defined in this Application, provided that one or more of the ring member carbon atoms indicated, is replaced by heteroatom moiety selected from -N=, -NR-, -O-, -S- or -S(O) 2 -, wherein R is hydrogen or (Cι- 6 )alkyl. For example, the instance wherem R 1 and R 2 together with the carbon atom to which both R 1 and R 2 are attached form hetero(C 3 . 8 )cycloalkyl" includes, but is not limited to, the following: in which R is hydrogen, (Cι_ 6 )alkyl, or a protecting group. "Heteroaryl" as a group or part of a group denotes an optionally substituted aromatic monocyclic or multicyclic organic moiety of about 5 to about 10 ring members in which one or more of the ring members is/are element(s) other than carbon, for example nitrogen, NR, oxygen or sulfur, wherein R is hydrogen, (Cι-6)alkyl, a protecting group or represents the free valence which serves as the point of attachment to a ring nitrogen. For example, optionally substituted hetero(C 5 -ι 0 )aryl as used in this Application includes, but is not limited to, 4-amino-2-hydroxypyrimidin-5-yl, benzothiazol-2-yl, lH-benzoimidazol-2-yl, 2-bromopyrid-5-yl, 5-bromopyrid-2-yl, 4-carbamoylthiazol-2-yl, 3-carboxypyrid-4-yl, 5-carboxy-2,6-dimethylpyrid-3-yl, 3 ,5-dimethylisoxazol-4-yl, 5-ethoxy-2,6-dimethylpyrid-3-yl, 5-fluoro-6-hydroxypyrimidin-4-yl, fur-2-yl, fur-3-yl, 5-hydroxy-4,6-dimethylpyrid-3-yl, 8-hydroxy-5,7-dimethylquinolin-2-yl, 5-hydroxymethylisoxazol-3-yl, 3-hydroxy-6-methylpyrid-2-yl, 3-hydroxypyrid-2-yl, lH-imidazol-2-yl, lH-imidazol-4-yl, lH-indol-3-yl, isothiazol-4-yl, isoxazol-4-yl, 2-methylfur-3-yl, 5-methylfur-2-yl, l-methyl-lH-imidazol-2-yl, 5-methyl- 3H-imidazol-4-yl, 5-methylisoxazol-3-yl, 5-methyl-2H-pyrazol-3-yl, 3-methylpyrid-2-yl, 4-methylpyrid-2-yl, 5-methylpyrid-2-yl, 6-methylpyrid-2-yl, 2-methylpyrid-3-yl, 2-methylthiazol-4-yl, 5-nitropyrid-2-yl, 2H-pyrazol-3-yl, 3H-pyrazol-4-yl, pyridazin-3-yl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, 5-pyrid-3-yl-2H-[l,2,4]triazol-3-yl, pyrimidin-4-yl, pyrimidin-5-yl, lH-pyrrol-3-yl, quinolin-2-yl, lH-tetrazol-5-yl, thiazol-2-yl, thiazol-5-yl, thien-2-yl, thien-3-yl, 2H-[l,2,4]triazol-3-yl, 3H-[l,2,3]triazol-4-yl, 5-trifluoromethylpyrid-2-yl, and the like. Suitable protecting groups include tert-butoxycarbonyl, benzyloxycarbonyl, benzyl, 4-methoxybenzyl, 2-nitrobenzyl, and the like. Optionally substituted hetero(C 5 _ιo)aryl as used in this Application to define R 5 includes lH-benzoimidazol-2-yl, pyrimidin-2-yl, benzooxazol-2-yl, benzothiazol-2-yl, pyridazin-3-yl, 3-phenyl-[l,2,4]oxadiazol-5-yl, 3-ethyl-[l,2,4]oxadiazol-5-yl, and the like. "Ηeterobicycloaryl" means bicycloaryl, as defined in this Application, provided that one or more of the ring carbon atoms indicated are replaced by a heteroatom moiety selected from -N=, -NR-, -O- or -S-, wherein R is hydrogen, (Cι. 6 )alkyl, a protecting group or represents the free valence which serves as the point of attachment to a ring nitrogen, and any carbocyclic ketone, thioketone or iminoketone derivative thereof. For example, optionally substituted hetero(C 8 .ιo)bicycloaryl as used in this Application includes, but is not limited to, 2-amino-4-oxo-3,4-dihydropteridin-6-yl, and the like. In general, the term heterobicycloaryl as used in this Application includes, for example, benzo[l,3]dioxol-5-yl, 3,4-dihydro-2H~[l,8jnaphthyridinyl, 3,4-dihydro-2H-quinolinyl, 2,4-dioxo-3,4-dihydro- 2H~quinazolinyl, l,2,3,4,5,6-hexahydro[2,2']bipyridinylyl, 3-oxo- 2,3-dihydrobenzo[l,4]oxazinyl, 5,6,7,8-tetrahydroquinolinyl, and the like. "Heterocycloalkyl" means cycloalkyl, as defined in this Application, provided that one or more of the ring carbon atoms indicated are replaced by a heteroatom moiety selected from -N=, -NR-, -O- or -S-, wherein R is hydrogen, (Cι_ 6 )alkyl, a protecting group or represents the free valence which serves as the point of attachment to a ring nitrogen, and any carbocyclic ketone, thioketone or iminoketone derivative thereof (e.g., the term hetero(C 5 .ιo)cycloalkyl includes imidazolidinyl, morpholinyl, piperazinyl, piperidyl, pyrrolidinyl, pyrrolinyl, quinuclidinyl, and the like. A ketone derivative of piperazinyl would be 3-oxo-piperazin-l-yl). Suitable protecting groups include tert-butoxycarbonyl, benzyloxycarbonyl, benzyl, 4-methoxybenzyl, 2-nitrobenzyl, and the like. Both the unprotected and protected derivatives fall within the scope of the invention. "Hydroxy" means the radical -OH. Unless indicated otherwise, the compounds of the invention containing hydroxy radicals include protected derivatives thereof. Suitable protecting groups for hydroxy moieties include benzyl and the like. "Iminoketone derivative" means a derivative containing the moiety -C(NR)-, wherem R is hydrogen or (Cι. 6 )alkyl. "Isomers" mean compounds of Formula I having identical molecular formulae but differ in the nature or sequence of bonding of their atoms or in the arrangement of their atoms in space. Isomers that differ in the arrangement of their atoms in space are termed "stereoisomers". Stereoisomers that are not mirror images of one another are termed "diastereomers" and stereoisomers that are nonsuperimposable mirror images are termed "enantiomers" or sometimes "optical isomers". A carbon atom bonded to four nonidentical substituents is termed a "chiral center". A compound with one chiral center has two enantiomeric forms of opposite chirality is termed a "racemic mixture". A compound that has more than one chiral center has 2 nΛ enantiomeric pairs, where n is the number of chiral centers. Compounds with more than one chiral center may exist as ether an individual diastereomers or as a mixture of diastereomers, termed a "diastereomeric mixture". When one chiral center is present a stereoisomer may be characterized by the absolute configuration of that chiral center. Absolute configuration refers to the arrangement in space of the substituents attached to the chiral center. Enantiomers are characterized by the absolute configuration of their chiral centers and described by the R- and S-sequencing rules of Cahn, Ingold and Prelog. Conventions for stereochemical nomenclature, methods for the determination of stereochemistry and the separation of stereoisomers are well known in the art (e.g., see "Advanced Organic Chemistry", 4th edition, March, Jerry, John Wiley & Sons, New York, 1992). It is understood that the names and illustration used in this Application to describe compounds of Formula I are meant to be encompassed all possible stereoisomers. Thus, for example, the name N-[l-(l-benzylcarbamoyl- methanoyl)-propyl] -4-mo holin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyramide is meant to include N-[(S)-l-(l-benzylcarbamoyl-methanoyl)-propyl]-4-morpholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramideandN-[(R)-l-(l-benzylcarbamoyl-methanoyl)-propyl]-4- morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyramide and any mixture, racemic or otherwise, thereof. "Ketone derivative" means a derivative containing the moiety -C(O)-. "Νitro" means the radical -ΝO 2 . "Optional" or "optionally" or "may be" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. For example, the phrase "wherein R 3 , R 4 and R 21 may be substituted further by 1 to 5 radicals..." means that R 3 , R 4 and/or R 21 may or may not be substituted in order to fall within the scope of the invention. "N-oxide derivatives" means derivatives of compounds of Formula I in which nitrogens are in an oxidized state (i.e., O-Ν) and which possess the desired pharmacological activity. "Pathology" of a disease means the essential nature, causes and development of the disease as well as the structural and functional changes that result from the disease processes. "Pharmaceutically acceptable" means that which is useful in preparing a pharmaceutical composition that is generally safe, non-toxic and neither biologically nor otherwise undesirable and includes that which is acceptable for veterinary use as well as human pharmaceutical use. "Pharmaceutically acceptable salts" means salts of compounds of Formula I which are pharmaceutically acceptable, as defined above, and which possess the desired pharmacological activity. Such salts include acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or with organic acids such as acetic acid, propionic acid, hexanoic acid, heptanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, o-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methylsulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2.2.2]oct-2-ene- 1-carboxylic acid, glucoheptonic acid, 4,4'-methylenebis(3-hydroxy-2-ene-l-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid and the like. Pharmaceutically acceptable salts also include base addition salts which may be formed when acidic protons present are capable of reacting with inorganic or organic bases. Acceptable inorganic bases include sodium hydroxide, sodium carbonate, potassium hydroxide, aluminum hydroxide and calcium hydroxide. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine, ttomethamine, N-methylglucamine and the like. "Prodrug" means a compound which is convertible in vivo by metabolic means (e.g. by hydrolysis) to a compound of Formula I. For example an ester of a compound of Formula I containing a hydroxy group may be convertible by hydrolysis in vivo to the parent molecule. Alternatively an ester of a compound of Formula I containing a carboxy group may be convertible by hydrolysis in vivo to the parent molecule. Suitable esters of compounds of Formula I containing a hydroxy group, are for example acetates, citrates, lactates, tartrates, malonates, oxalates, salicylates, propionates, succinates, fumarates, maleates, methylene-bis-b-hydroxynaphthoates, gentisates, isethionates, di- 7-toluoyltartrates, methylsulphonates, ethanesulphonates, benzenesulphonates, p-toluenesulphonates, cyclohexylsulphamates and quinates. Suitable esters of compounds of Formula I containing a carboxy group, are for example those described by F.J.Leinweber, Drug Metab. Res., 1987, 18, page 379. An especially useful class of esters of compounds of Formula I containing a hydroxy group, may be formed from acid moieties selected from those described by Bundgaard et al., J. Med. Chem., 1989, 32, page 2503-2507, and include substituted (aminomethyl)-benzoates, for example, dialkylamino- methylbenzoates in which the two alkyl groups may be joined together and/or interrupted by an oxygen atom or by an optionally substituted nitrogen atom, e.g. an alkylated nitrogen atom, more especially (morpholino-methyl)benzoates, e.g. 3- or 4-(morpholinomethyl)- benzoates, and (4-alkylpiperazin-l-yl)benzoates, e.g. 3- or 4-(4-alkylpiperazin-l-yl)benzoates. "Protected derivatives" means derivatives of compounds of Formula I in which a reactive site or sites are blocked with protecting groups. Protected derivatives of compounds of Formula I are useful in the preparation of compounds of Formula I or in themselves may be active cathepsin S inhibitors. A comprehensive list of suitable protecting groups can be found in T.W. Greene, Protecting Groups in Organic Synthesis, 3rd edition, John Wiley & Sons, Inc. 1999. "Therapeutically effective amount" means that amount which, when administered to an animal for treating a disease, is sufficient to effect such treatment for the disease. "Thioketone derivative" means a derivative containing the moiety -C(S)-. "Treatment" or "treating" means any administration of a compound of the present invention and includes: (1) preventing the disease from occurring in an animal which may be predisposed to the disease but does not yet experience or display the pathology or symptomatology of the disease, (2) inhibiting the disease in an animal that is experiencing or displaying the pathology or symptomatology of the diseased (i.e., arresting further development of the pathology and/or symptomatology), or (3) ameliorating the disease in an animal that is experiencing or displaying the pathology or symptomatology of the diseased (i.e., reversing the pathology and/or symptomatology) . Nomenclature: The compounds of Formula I and the intermediates and starting materials used in their preparation are named in accordance with IUPAC rules of nomenclature in which the characteristic groups have decreasing priority for citation as the principle group as follows: acids, esters, amides, etc. Alternatively, the compounds are named by AutoNom 4.0 (Beilstein Information Systems, Inc.). For example, a compound of Formula I in which R 1 is hydrogen, R 2 is propyl, R 3 and R 4 are each benzylsulfonylmethyl; that is, a compound having the following structure: is named N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-butyl]-3-benzylsulfonyl-2-benzyl- sulfonylmethyl-propionamide; With reference to formula (I) above, the following are particular and preferred groupings: X 1 may particularly represent -C(R 1 )(R 2 )X 2 in which R 1 is hydrogen or (Cι. 6 )alkyl and R 2 is hydrogen, -X 4 OR 13 or -R 15 , in which within R 15 any aryl, heteroaryl, cycloalkyl or heterocycloalkyl may be substituted with 1 to 3 radicals independently selected from (Cι. 6 )alkyl, cyano, halo, halo-substituted(C 1 . 4 )alkyl, nitro, -X 4 ΝR 12 R 12 , -X 4 NR 12 C(O)R 12 , - X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , - X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 wherein X 4 is a bond or (Cι. 6 )alkylene, R 12 at each occurrence independently is hydrogen or (Cι. 6 )alkyl, R 13 is hydrogen, (Cι. 6 )alkyl or halo-substituted(Cι. 6 )alkyl, R 14 is (Cι. 6 )alkyl or halo-substituted(C 1 . 6 )alkyl; and X 2 is cyano, -CHO, -C(O)R 5 , -C(O)CF 3 , -C(O)CF 2 CF 2 R 9 -CH=CHS(O) 2 R 5 , -C(O)CF 2 C(O)NR 5 R 6 , -C(O)C(O)NR 5 R 6 , -C(O)C(O)OR 5 , -C(O)CH 2 OR 5 , -C(O)CH 2 N(R 6 )SO 2 R 5 , -C(O)C(O)N(R 6 )(CH 2 ) 2 OR 6 , -C(O)C(O)N(R 6 )(CH 2 ) 2 NR 6 or -C(O)C(O)R 5 ; wherein R 5 is (C^alkyl, (C 6 .io)aryl(C 0 - 6 )alkyl, hetero(C 4 .ιo)aryl(C 0 - 6 )alkyl, (C 4 .ιo)cycloalkyl(C 0 . 6 )alkyl or hetero(C 4 .ιo)cycloalkyl(C 0 - 6 )alkyl, R 6 is hydrogen or (Cι_ 6 )alkyl and R 9 is halo. X 1 may also particularly represent -C(R ! )(R 2 )X 2 in which R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene or hetero(C 3 . 8 )cycloalkylene, in which the cycloalkylene or the heterocycloalkylene is optionally substituted with 1 to 3 radicals independently selected from (Cι. 6 )alkyl and hydroxy and X 2 is cyano, -CHO, -C(O)R 5 , -C(O)CF 3 , -C(O)CF 2 CF 2 R 9 -CH=CHS(O) 2 R 5 , -C(O)CF 2 C(O)NR 5 R 6 , -C(O)C(O)NR 5 R 6 , -C(O)C(O)OR 5 , -C(O)CH 2 OR 5 , -C(O)CH 2 N(R 6 )SO 2 R 5 , -C(O)C(O)N(R 6 )(CH 2 ) 2 OR 6 , -C(O)C(O)l -C(O)C(O)R 5 . X 1 may also particularly represent -X 3 , wheein X 3 is a group of formula (b): (b) in which n is 1 or 2, z is 0 or 1, X 6 is O or NR 11 , wherein R 11 is selected from hydrogen (C 1 . 6 )alkyl, - X 4 C(O)OR 12 , -X 4 OC(O)R 12 , -X 4 C(O)R 13 , -X 4 S(O) 2 R 12 , -X 4 S(O) 2 R 15 , ' -X 4 C(O)R 15 and -X 4 C(O)OR 15 , in which X 4 is a bond or (C w )alkylene; R 12 at each occurrence independently is hydrogen or (Cι. 6 )alkyl; R 13 is hydrogen, (Cι. 6 )alkyl or halo-substituted(Cι. 6 )alkyl and R 15 is (C 3 . 10 )cycloalkyl(C 0 - 6 )alkyl, hetero(C 3 . 10 )cycloalkyl(C 0 - 3 )alkyl, (C 6 .ιo)aryl(C 0 - 6 )aIkyl, hetero(C 5 -ιo)aryl(C 0 . 6 )alkyl, (C 9 .i 2 )bicycloaryl(Co- 6 )alkyl or hetero(C 8 .ι 2 )bicycloaryl(C 0 - 6 )alkyl; within X 3 any cycloalkyl or heterocycloalkyl group may be optionally substituted by substituted further by 1 to 5 radicals independently selected from (Cι_ 6 )alkyl, cyano, halo, halo-substituted(Cι. 4 )alkyl, nitro, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(0)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , - X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 and/or 1 radical selected from -R 15 , - OR 15 , -SR 15 , -S(O)R 15 , -S(O) 2 R 15 , -C(O)R 15 , -C(O)OR 15 , -OC(O)R 15 , -NR 15 R 12 , -NR 12 C(O)R 15 , -NR 12 C(O)OR 15 , -C(O)NR 15 R 12 , -S(O) 2 NR 15 R 12 , -NR 12 S(O) 2 R 15 , -NR 12 C(O)NR 15 R 12 and -NR 12 C(NR 1 )NR 15 R 12 wherein X 4 is a bond or (Cι. 6 )alkylene, R 12 at each occurrence independently is hydrogen or (Cι. 6 )alkyl, R 13 is hydrogen, (Cι_ 6 )alkyl or halo-substituted(C 1 . 6 )alkyl, R 14 is (Cι. 6 )alkyl or halo-substituted(Cι. 6 )alkyl and R 15 is (C 3 _ 10 )cycloalkyl(Co. 6 )alkyl, (C 3 .ιo)cycloalkyl(C 0 . 6 )alkyl, hetero(C 3 .ι 0 )cycloalkyl(C 0 - 3 )alkyl, (C 6 . ιo)aryl(C 0 - δ )alkyl, hetero(C 5 .ιo)aryl(C 0 - 6 )alkyl, (C 9 .ι 2 )bicycloaryl(C 0 - 6 )alkyl or hetero(C 8 .ι 2 )bicycloaryl(C 0 - 6 )alkyl; R 3 and R 4 may particularly represent -C(R 16 )(R 17 )X 7 , wherein R 16 and R 17 are hydrogen, (Cι- 6 )alkyl or fluoro, or R 16 is hydrogen and R 17 is hydroxy and X 7 is selected from -X 4 SR 13 , -X 4 C(O)R 13 , -X 4 C(O)NR 12 R 12 , -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 and -X 4 C(O)NR 15 R 12 , wherein X 4 is a bond or (Cι. 6 )alkylene, R 12 at each occurrence independently is hydrogen or (Cι. 6 )alkyl, R 13 is hydrogen, (Cι. 6 )alkyl or halo-substituted(Cι. 6 )alkyl, R 14 is (Cι. 6 )alkyl or halo-substituted(Cι. 6 )alkyl and R 15 is (C 3 .ιo)cycloalkyl(Co- 6 )alkyl, (C 3 . 1 o)cycloalkyl(Co- 6 )alkyl, hetero(C 3 .ιo)cycloalkyl(Co. 3 )alkyl, (C 6 -ιo)aryl(C 0 - 6 )alkyl, hetero(C 5 ..ιo)aryl(Co. 6 )alkyl, (C 9 .ι 2 )bicycloaryl(C 0 . 6 )alkyl or hetero(C 8 .ι 2 )bicycloaryl(C 0 - 6 )alkyl; within R 3 and R 4 may be substituted further by 1-5 radicals independently selected from (C ! . 6 )alkyl, cyano, halo, halo-substituted(C 1 . 4 )alkyl, -X 4 NR 12 C(O)OR 12 , -X 4 OR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 and -X 4 S(O) 2 R 14 and one of R 3 or R 4 may be further substituted with 1 radical selected from -R 15 and -X 4 OR 15 , wherein X 4 is a bond or (Cι_ 6 )alkylene, R 12 at each occurrence independently is hydrogen or (Cι- 6 )alkyl, R 13 is hydrogen, (Cι_ 6 )alkyl or halo-substituted(Cι. 6 )alkyl, R 14 is (Cι. 6 )alkyl or halo-substituted(Cι. 6 )alkyl and R 15 is (C 3 .ι 0 )cycloalkyl(C 0 - 6 )alkyl, (C 3 .ιo)cycloalkyl(Co- 6 )alkyl, hetero(C 3 . 10 )cycloalkyl(C 0 - 3 )alkyl, (C 6 -ιo)aryl(C 0 . 6 )alkyl, hetero(C 5 _io)aryl(C 0 - 6 )alkyl, (C 9 . 12 )bicycloaryl(C 0 . 6 )alkyl or hetero(C 8 .ι 2 )bicycloaryl(C 0 - 6 )alkyl. R 3 and R 4 groups include allylsulfonylmethyl, benzylcarbamoyl-methyl, benzyl, benzylsulfanylmethyl, 2-benzenesulfonyl-ethyl, benzenesulfonylmethyl, 2-benzo[l,3]dioxol-5-yl-2-oxo-ethyl, 2-benzo[b]thiophen-2-yl-2-oxo-ethyl, biphenyl-2-ylmethylsulfonylmethyl, biphenyl-4-ylmethyl-sulfonylmethyl, biphenyl-3-ylmethyl, biphenyl-4-ylmethyl, 2-biphenyl-4-yl-2-oxo-ethyl, 3,5-bis-trifluoromethyl-benzyl-sulfonylmethyl, 3-bromo-benzyl, 2-oxo-2-pyrrolidin-l-yl-ethyl, 2-bromό-benzyl-sulfonylmethyl, (butyl-methyl-carbamoyl)-methyl, 4-tert-butyl-benzylsulfonylmethyl, (3-carbamoyl-phenylcarbamoyl)-mefhyl, (4-carbamoyl-phenylcarbamoyl)-methyl, 4-carboxy-benzylsulfonylmethyl, 2-(3-chloro-benzo[b]thiophen-2-yl)-2-oxo-ethyl, 2-(4'-chloro-biphenyl-4-yl)-2-oxo-ethyl, 3-chloro-2-fluoro-benzylsulfonylmethyl, 2-chloro-benzylsulfonylmethyl, 3-chloro-benzylsulfonylmethyl, 4-chloro-benzylsulfonylmethyl, 2-(4-chloro-phenyl)-2-oxo-ethyl, 5-chloro-thiophen-2-ylmethylsulfonylmethyl, 2-(3-chloro-thiophen-2-yl)-2-oxo-ethyl, 2-chloro-5-trifluoromethylbenzylsulfonylmethyl, (cyanomethyl-methyl-carbamoyl)-methyl, cyclohexylcarbamoylmethyl, 2-cyclohexyl-ethanesulfonyl, cyclohexylmethyl- sulfonylmethyl, 2-cyclohexyl-ethyl, cyclohexylmethyl, 2-cyano-benzylsulfonylmethyl, cyclopropylmethylsulfonylmethyl, 3-cyano-benzylsulfonylmefhyl, 4-cyano-benzylsulfonylmethyl, 2,5-dichloro-benzylsulfonylmethyl, 2,6-dichloro-benzylsulfonylmethyl, 3,4-dichloro-benzylsulfonylmethyl, 2-[2-(l , 1 -difluoro-methoxy)-benzenesulfonyl]-ethyl, 2-[3-(l , l-difluoro-methoxy)-benzenesulfonyl]-ethyl, 2-[4-(l,l-difluoro-methoxy)-benzenesulfonyl]-efhyl, 2-( 1 , 1 -difluoro-methoxy)-benzylsulfonylmethyl, 3-(l , l-difluoro-methoxy)-benzylsulfonylmethyl, 4-( 1 , 1 -difluoro-methoxy)-benzylsulfonylmethyl, 2,3-difluoro-benzylsulfonylmethyl, 2,4-difluoro-benzylsulfonylmethyl, 2,5-difluoro-benzylsulfonylmethyl, 2,6-difluoro-benzylsulfonylmethyl, 3,4-difluoro-benzylsulfonylmethyl, 3,4-dichloro-benzyl-sulfonylmethyl, 2-(3,4-difluoro-phenyl)-2-oxo-ethyl, 2-(3,4-dimethoxy-phenyl)-2-oxo-ethyl, 4-dimethylcarbamoylmethyl, 3,5-dimethyl-isoxazol-4-ylmethylsulfonylmethyl, 3,5-dimethyl-benzylsulfonylmethyl, 2-(3-fluoro-4-methoxy-phenyl)-2-oxo-ethyl, 2-fluoro-3-methyl-benzylsulfonylmethyl, 2-fluoro-benzylsulfonylmethyl, 3-fluoro-benzylsulfonylmethyl, 4-fluoro-benzylsulfonylmethyl, 2-(4-fluoro-phenyl)-2-oxo-ethyl, 4-fluoro-2-trifluoromethoxy-benzyl-sulfonylmethyl, 2-fluoro-3-trifluoromethylbenzylsulfonylmetlιyl, 2-fluoro-4-trifluoromethylphenyl-methylsulfonylmethyl, 2-fluoro-5-trifluoromethylbenzyl- sulfonylmethyl, 2-fluoro-6-trifluoromethyl-benzylsulfonylmethyl, 4-fluoro-3-trifluoromethyl-benzylsulfonylmethyl, 2-(4-hydroxy-phenyl)-2-oxo-ethyl, isobutylsulfanylmethyl, isopropylcarbamoyl-methyl, 2-(4-methylsulfonylamino-phenyl)-2-oxo-ethyl, 2-(4-methylsulfonyl-piperazin-l-yl)-2-oxo-ethyl, 5-methyl-2-oxo-hexyl, 2-methoxy-benzyl-sulfonylmethyl, 4-methoxy-benzylsulfonylmethyl, 2-(4-methoxy-phenyl)-2-oxo-ethyl, 3-methyl-benzylsulfonylmethyl, 2-methyl-propane- 1 -sulfonyl, 2-(5-methyl-thiophen-2-yl)-2-oxo-efhyl, 2-methyl-thiazol-4- yl-methylsulfonylmethyl 5-methyl-thiophene-2-sulfonylmethyl, naphthalen-2-yl, naphthalen-2-ylmethylsulfonylmethyl, 2-naphthalen-2-yl-2-oxo-ethyl, naphthalene-2-sulfonylmethyl, 2-morpholin-4-yl-2-oxo-ethyl, 2-oxo-2-piperidin-l-yl-ethyl, 2-oxo-2-(4-phenoxy-phenyl)-ethyl, 2-oxo-2-phenyl-ethyl, 2-oxo-2-pyrrolidin- 1 -yl-ethyl, 2-oxo-2-thiophen-2-yl-ethyl, 2-oxo-2-thiophen-3-yl-ethyl, 2-oxo-2-p-tolyl~ethyl, 2-oxo-2-(4-trifluoromethoxy-phenyl)-ethyl, l-oxy-pyridm-2-ylmethylsulfonylmefhyl, phenylcarbamoylmefhyl, 2-benzylsulfonyl-ethyl, benzylsulfonylmethyl, 4-benzylsulfonylmethyl, 2-phenylsulfanyl-ethyl, prop-2-ene- 1 -sulf onylmethyl, pyridin-3-ylcarbamoylmemyl,pyridin-4-ylcarbamoylmemyl,2-(pyridine-2-sulfonyl)-emyl, 2-(ρyridine-4-sulfonyl)-ethyl, pyridin-2-ylmethylsulfonylmethyl, pyridin-3-ylmethylsulfonylmethyl, pyridin-4-ylmethylsulfonylmethyl, (5,6,7,8-tetrahydro-naphthalen-l-ylcarbamoyl)-methyl, tetrahydropyran-4-yloxymethyl, thiophene-2-sulfonylmethyl, o-tolylmethylsulfonylmethyl, m-tolylmethylsulfonylmethyl, p-tolylmethylsulfonylmethyl, 2-(2-trifluoromethoxy-benzenesulfonyl)-ethyl, 2-(3-trifluoromethoxy-benzenesulfonyl)-ethyl, 2-(4-trifluoromethoxy-benzenesulfonyl)-ethyl, 2-trifluoromethoxy-benzylsulfanylmethyl, 2-trifluoromethoxy-benzylsulfonylmethyl, 3-trifluoromethoxy-benzylsulfonylmethyl, 4-trifluoromethoxy-benzylsulfonylmethyl, 2-trifluoromethyl-benzylsulfanylmethyl, 2-trifluoromethyl-benzylsulfonylmethyl, 3-trifluoromethyl-benzylsulfonylmethyl, 4-trifluoromethyl-benzylsulfonylmethyl, 2,3,4-trifluoro-benzylsulfonylmethyl, 2,3,5-trifluoro-benzylsulfonylmethyl, 2,4,5-trifluoro-benzylsulfonylmethyl, 2,4,6-trifluoro-benzylsulfonylmethyl and 2,5,6-trifluoro-benzylsulfonylmefhyl. Preferred R 3 and R 4 groups include allylsulfonylmethyl, benzylsulfanylmethyl, 3-cyano-benzyl- sulfonylmethyl, cyclohexylmethyl, 2-difluoromethoxy-benzylsulfonylmethyl, isobutylsulfanylmethyl, (2-methyl-thiazol-4-yl)-methylsulfonylmethyl, 2-morpholin-4-yl-2-oxo-efhyl, 2-oxo-2-piperidin- 1 -yl-ethyl, 2-oxo-2-pyrrolidin- 1 -yl-ethyl, benzylsulfonylmethyl, tetrahydropyran-4-yloxymethyl, and 3-trifluoromethyI-benzylsulfonylmethyl. Particularly preferred R 3 and R 4 groups include benzylsulfanylmethyl, 2-difluoromethoxy-benzylsulfonylmethyl, 2-morpholin-4-yl-2-oxo-ethyl and benzylsulfonylmethyl. It is to be understood that this invention covers all appropriate combinations of the particular and preferred groupings referred to herein unless otherwise stated A particular preferred group of compounds of the invention are compounds of formula 1(a): 1(a) wherein R 1 , R 2 and X 7 are as hereinbefore described, and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds of formula 1(a) and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Compounds of formula 1(a) in which R 1 is hydrogen and R 2 is: (i) hydrogen; (ii) -X 4 OR 13 , e.g., -CH 2 -O-CH 3 or -CH 2 -CH 2 -O-CH 3 ; (iii) hetero(C 5 .ιo)aryl(C 0 - 6 )alkyl, e.g., thien-2-yl or 5-methylfuran-2-yl; (iv) (C 5 .ιo)aryl(C 0 .6)alkyl, e.g., phenethyl; (v) (Cι. 6 )alkyl, e.g. ethyl, n-propyl or n-butyl] are preferred. Compounds of formula 1(a) in which R 1 and R 2 are both methyl are also preferred. Compounds of formula 1(a) in which R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene, e.g., cyclopropyl, or hetero(C 3 . 8 )cycloalkylene, e.g., tetrahydropyran-4-yl andN-methylpiperidin-4-yl, are also preferred. Compounds of formula 1(a) in which X 7 is: (i) -R 15 or -R 13 , e.g., ( ) or -CH=CH 2 , respectively; (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and R 15 i is hetero(C 3 .ιo)cycloalkyl(C 0 . 6 )alkyl, e.g., -c (O) — Ν 0 ; (iii) -X 4 OR 15 in which X 4 is a direct bond and R 15 is hetero(C3_χo)cycloalkyl(Co_6)alkyl, e.g., -0 — ( O ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (d. 6 )alkylene, R 13 is ( ^alkyl and R 15 is (C 6 .ι 0 )aryl(C M )al yl, e.g., -s-CBL — ( , (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R 13 is (Cι. 6 )alkyl and R 15 is (C 6 .ι 0 )aryl(C 0 . 6 )alkyl, e.g., -SO 2 -CH 2 - -S0 2 -CH 2 ~ // w are preferred. Compounds of formula 1(a) in which X 7 represents -c (0) — N ' 0 , are especially preferred. A preferred group of compounds of the invention are compounds of formula 1(a) in which: R 1 is hydrogen and R 2 is (i) hydrogen, (ii) X 4 OR 13 , e.g. -CH 2 -O-CH 3 or-CH 2 -CH 2 - O-CH 3 , (iii) hetero(C 5 .ιo)aryl(Co- 6 )alkyl, e.g. thien-2-yl or 5-mefhylfuran-2-yl, (iv)(C 5 . 10 )aryl(Co- 6 )alkyl, e.g. phenethyl or (v) (Cι_g)alkyl, e.g. ethyl, n-propyl or n-butyl; X 7 is (i) -R 13 or-R 15 , e.g. <^ \ or -CH=CH 2 , respectively, (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and R 15 is hetero(C 3 .ιo)cycloalkyl(Co- δ )alkyl, e.g. -c (O) — N O , -C (O) — N > or -c (0) — N , (iii) -X 4 OR 15 in which X 4 is a direct bond and R 15 is hetero(C 3 .ιo)cycloalkyl(Co- 6 )alkyl, e.g. X 4 is a direct bond or (Cι. 6 )alkylene, R 13 is (Cι. 6 )alkyl and R 15 is (C 6 . 1 o)aryl(C 0 - 6 )alkyl, e.g. -S-CHr o „r -C „H„ 2 -S „ or (v) or X 4 S(O) 2 R 15 in which X 4 is a direct bond, R 13 is (Cι. 6 )alkyl and R 15 is (C 6 .ι 0 )aryl(C 0 . 6 )alkyl, e.g. -SO 2 -CH 2 -CH=CH 2 , -CH,-SO r V - SCL-CHr w , and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their Ν-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(a) in which: R 1 andR 2 are both methyl; X 7 is (i)-R 15, e.g. ( \ or -CH=CH 2 , (ii) -X 4 C(O)R 12a in which X 4 is a direct bond andR 12 is hetero(C3_ιo)cycloalkyl(Co_6)al yl, e.g. -c (O) — o , -C (O) — Ν > or -c (O) — Ν , in which X 4 is a direct bond and R 5 is hetero(C3_χo)cycloalkyl(Co-6)alkyl, e.g. -o — ( 0 ; (iv) -X SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (C 1 _6)alkylene, Rl3 i s (Ci_ 6 )alkyl andR 15 is (C 6 . 10 )aryl(Co-6)alkyl, e.g. -s-CH 2 — , -S-CH 2 — < y or -CH 2 -S < ^ or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R 3 is (Cι_ 6 )alkyl and R 13 is (C 6 .ιo)aryl(C 0 .6)alkyl, e.g. . -SO 2 -CH 2 -CH=CH 2 , -CH 2 -SO- w -S0 2 -CH- / \ and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(a) in which: R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (i) (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or (ii) hetero(C 3 . 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl; X 7 is (i) -R 15 or -R 13 , e.g. ( \ or -CH=CH 2; respectively (ϋ) -X 4 C(O)R 15 in which X 4 is a direct bond and R 15 is hetero(C3_io)cycloalkyl(Co-6)aikyl, e.g. -c (O) — N o , -C (O) — N or -C {0) — N , (iii) -X 4 OR 15 in which X 4 is a direct bond and R 15 is hetero(C3_ιo)cycloalkyl(C 0 -6)alkyl, e.g. -o— ( 0 ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cχ_6)alkylene, R 13 is (Cι_g)alkyl and R 15 is (C6_ιo) ar y 1 (Cθ- 6)alkyl, e.g. -S-CH 2 -S-CH or -CH„-S" or (v) ( \ -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R 13 is (C 1 . 6 )alkyl and R 15 is (C6-lo) r y Co-6)alkyl, e.g. -S0 2 -CH 2 - // w and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Another particular group of compounds of the invention are compounds of formula 1(b): 1(b) wherein R 1 , R 2 and X 7 are as hereinbefore described, and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds of formula 1(b) and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Compounds of formula 1(b) in which R 1 is hydrogen and R 2 is: (vi) hydrogen; (vii) -X 4 OR 13 ' e.g. -CH 2 -O-CH 3 or -CH 2 -CH 2 -O-CH 3 ; (viii) hetero(C 5 -ιo)aryl(Co- 6 )alkyl, e.g. thien-2-yl or 5-methylfuran-2-yl; (ix) (C 5 .ιo)aryl(Co- 6 )alkyl, e.g. phenethyl; (x) (Cι_ 6 )alkyl, e.g. ethyl, n-propyl or n-butyl are preferred. Compounds of formula 1(b) in which R 1 and R 2 are both methyl are also preferred. Compounds of formula 1(b) in which R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or hetero(C 3 - 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl are also preferred. Compounds of formula 1(b) in which R 7 and R 8 together form oxo are preferred. Compounds of formula 1(b) in which R 5 is lH-benzoimidazol-2-yl, pyrimidin-2-yl, benzooxazol-2-yl, benzothiazol-2-yl, pyridazin-3-yl, 3-phenyl-[l,2,4]oxadiazol-5-yl, 3-ethyl-[l,2,4]oxadiazol-5-yl are preferred. Compounds of formula 1(a) in which X 1 : i,s (vi) -R 15 or- - 13 'e.g. or -CΗ=CΗ 2 ; (vii) -X 4 C(O)R 15 in which X 4 is a direct bond and R 15 i is hetero(C3_χo)cycloalkyl(Co_6)alkyl, e.g. -C (O) — Ν o , (viii) -X 4 OR 15 in which X 4 is a direct bond and R 15 is hetero(C3_io)cycloalkyl(Co-6)alkyl, e.g. -0 — ( 0 ; (ix) -X 4 SR 13 or -R 15 in which X 4 is a direct bond or (C 1 . 6 )alkylene, R* 3 is (Cχ_6)alkyl and R , 1"5 is (C _ιo)aιyl(Ctø_6)a]kyl, e.g. -s-CH. (x) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R*3 i s (Chalky! and R 15 is (C 6 . 10 )aryl(Co.6)alkyl, e.g. -SO 2 -CH 2 - are preferred. Compounds of formula 1(b) in which X represents -c (0) — N 0 , -S-CH 2 — (/ γ , -SO 2 -CH 2 — f y or are especially preferred. A preferred group of compounds of the invention are compounds of formula 1(b) in which: R 1 is hydrogen and R 2 is (i) hydrogen, (ii) X 4 OR 13 , e.g. -CH 2 -O-CH 3 or-CH 2 -CH 2 -O-CH 3 , (iii) hetero(C5-ιo)aryl(Co-6)alkyl, e.g. thien-2-yl or 5-methylfuran-2-yl, (iv)(C 5 .ιo)aryl(Co- 6 )alkyl, e.g. phenethyl or (v) (Cι. 6 )alkyl, e.g. ethyl, n-propyl or n-butyl; R 7 and R 8 together form oxo; R 5 is lH-benzoimidazol-2-yl, pyrimidin-2-yl, benzooxazol-2-yl, benzothiazol-2-yl, pyridazin-3-yl, 3-phenyl-[l,2,4]oxadiazol-5-yl, 3-ethyl-[l,2,4]oxadiazol-5-yl; X7 is (i) -R 15 ' e.g. (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and R 15 is hetero(C3_ιo)cycloalkyl(C()-6)alkyl or -C (O) — N (iii) -X 4 OR 15 in which X 4 is a direct bond and R^ is hetero(C3_χo)cycloalkyl(Cθ-6)alkyl, e.g. -0 — ( 0 ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (C 1 _6)alkylene, R 13 is (Chalky! and R 15 is (C6_ιo)aryl(Cθ-6)alkyl, e.g. -S-CH 2 or -CH 2 -S or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R 13 is (Cχ. 6 )alkyl and R .1 l 5 D is (C 6 _ιo)aryl(C 0 -6)alkyl, e.g. . -SO 2 -CH 2 -CH=CH 2 , -S0 2 -CH 2 s , -S0 2 -CH 2 f 7 or ; and their F 2 HCO F 3 C corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(b) in which: R 1 and R 2 are both methyl; R 7 and R 8 together form oxo; R 5 is lH-benzoimidazol-2-yl, pyrimidin-2-yl, benzooxazol-2-yl, benzofhiazol-2-yl, pyridazin-3-yl, 3-phenyl-[l,2,4]oxadiazol-5-yl, 3-ethyl-[l,2,4]oxadiazol-5-yl; X7 is (i) -R 14a - e.g. \ or -CΗ=CΗ 2 , (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and R 15 is hetero(C3_χo)cycloalkyl(Cθ-6)alkyl, e.g. -c (O) — N O , -C (O) — N > or -C (O) — N 1 , (iii) -X 4 OR 15 in which X 4 is a direct bond and R 1 ^ is hetero(C3_io)cycloalkyl(Co-6)alkyl, e.g. ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cχ_6)alkylene, R 13 is (Cχ_6)alkyl and R 15 is (Cg.K^ ry )- 6)alkyl, e.g. -S-CH 2 -S-CH- r-O or -CH 2 -S- or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, Rl3 is (Cι_6)alkyl and R 15 is (C6-lo)aryl(Co-6)alkyl, e.g. o o r r and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(b) in which: R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (i) (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or (ii) hetero(C 3 . 8 )cycloalkylene, e.g. texrahydropyran-4-yl and N-mefhylpiperidin-4-yl; R 7 and R 8 together form oxo; R 5 is lH-benzoimidazol-2-yl, pyrimidin-2-yl, benzooxazol-2-yl, benzothiazol-2-yl, pyridazin-3-yl, 3-phenyl-[l,2,4]oxadiazol-5-yl, 3-ethyl-[l,2,4]oxadiazol-5-yl;X 7 is (i)-R 15 or -R 13 ' e.g. \ or -CΗ=CΗ 2; respectively (ϋ) -X 4 C(O)R 15 in which X 4 is a / \ direct bond and Rl5 is hetero(C3_χo)cycloalkyl(Co_6)alkyl, e.g. -c (O) J 0 \ / (iii) -X 4 OR 15 in which X 4 is a direct bond and Rl5 is hetero(C3_ 10 )cycloalkyl(Co-6)alkyl, e.g. ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cχ_6)alkylene, R 13 is (Cχ_6)alkyl andR 15 is (C6_ιo) ryl(Cθ- 6)alkyl, e.g. -S-CH- -S-CH- // w or -CH 2 -S -M or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, Rl is (C 1 . 6 )alkyl and R 15 is (C6-10)aryl(C 0 -6)alkyl, e.g. . -S0 2 -CH 2 f J , -S0 2 - - SO J 2 - CH if v or and their corresponding N-oxides, and F 3 C their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Another particular group of compounds of the invention are compounds of formula 1(c): 1(c) wherein R 1 , R 2 and X 7 are as hereinbefore described, and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds of formula 1(c) and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Compounds of formula 1(c) in which R 1 is hydrogen and R 2 is: (xi) hydrogen; (xii) -X 4 OR 13 'e.g. -CH 2 -O-CH 3 or-CH 2 -CH 2 -O-CH 3 ; (xiii) hetero(C 5 .i 0 )aryl(C 0 - 6 )alkyl, e.g. thien-2-yl or 5-methylfuran-2-yl; (xiv) (C 5 . 10 )aryl(Co. 6 )alkyl, e.g. phenethyl; (xv) (Cι. 6 )alkyl, e.g. ethyl, n-propyl or n-butyl are preferred. Compounds of formula 1(c) in which R 1 and R 2 are both methyl are also preferred. Compounds of formula 1(c) in which R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or hetero(C 3 . 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl are also preferred. Compounds of formula 1(c) in which R 5 is (C 6 .ιo)aryl(C 0 - 6 )alkyl, e.g. phenyl are preferred. Compounds of formula 1(a) in which X 7 is: (xi) -R 15 or -R 13 , e.g. / \ or -CH=CH 2> respectively; (xii) -X 4 C(O)R 15 in which X 4 is a direct bond and Rl5 i is hetero(C3_ιo) y c l°alkyl(Co_6)alkyl, e.g. -C (O) — N 0 , (xiii) -X 4 OR 15 in which X 4 is a direct bond and R 15 i is hetero(C3_ιo)cycloalkyl(C()-6)alkyl, e.g. -o — ( 0 ; (xiv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (C ^alkylene, R 13 is (Cι_6)aιkyl and R 15 is (C _ιo)aιyl(Co_6)alkyl, e.g. -s-CH — ( , (xv) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, Rl3 is (Cι_ 6 )alkyl and R 15 is (C 6 . 10 )aryl(Co-6)alkyl, e.g. -SO 2 -CH 2 - CH=CH 2) -CH 2 -SO- ,-ts. -S0 2 -CH 2 - w are preferred. Compounds of formula 1(c) in which X 7 represents -c (0) — N /~\ O . -S-CH 2 — f x ) , -S0 2 - are especially preferred. A preferred group of compounds of the invention are compounds of formula 1(c) in which: R 1 is hydrogen andR 2 is (i) hydrogen, (ii) X 4 OR 13 'e.g. -CH 2 -O-CH 3 or-CH 2 -CH 2 -O-CH 3 , (iii) hetero(C 5 .ιo)aryl(C 0 - 6 )alkyl, e.g. thien-2-yl or 5-methylfuran-2-yl, (iv)(C 5 .ιo)aryl(Co- 6 )alkyl, e.g. phenethyl or (v) (Cι_ 6 )alkyl, e.g. ethyl, n-propyl or n-butyl; R 5 is(C 6 .ιo)aryl(C 0 - 6 )alkyl,e.g.phenyl;X 7 is(i)-R 15 or-R 13 ,e.g. \ or-CH=CH 2> respectively' (ϋ) -X 4 C(O)R 15 in which X 4 is a direct bond and Rl5 i s hetero(C3_io)cycloalkyl(Co-6)alkyl, e.g. -c(0)— 0, -C(O)— > or -C(O)— N ] , (iii) -X 4 OR 15 in which X 4 is a direct bond and R 15 is hetero(C 3 .io)cycloalkyl(Co-6)alkyl, e.g. -o — O ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cχ_6)alkylene, R* j s (Cι_g)alkyl and R 15 is (C6_ιo)aryl(Co_ 6)alkyl, e.g. -S-CH 2 — , or -CH,-S -M or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R 13 is (Chalky! and R 15 is (C6-lθ)aryl(Cθ-6)alkyl, e.g. -SO n -CH; r- V ; and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(c) in which: R 1 and R 2 are both methyl; R 5 is (C 6 .ι 0 )aryl(C 0 - 6 )alkyl, e.g. phenyl; X 7 is (i) -R 15 or -R 13> e.g. \ or -CH=CH 2 , (ii) -X 4 C(O)R 15 in which X 4 is a direct bond, R 15 is hetero(C3_ιo)cycloalkyl(C()-6)alkyl, e- - -C (O) — N 0 , -C (O) — N or -C ( O ) — N , (iii) -X 4 OR 15 in which X 4 is a direct bond and R 15 is hetero(C3_ 1 o)cycloalkyl(Co_6)alkyl, e.g. -o — 0 ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cχ_6)alkylene, Rl3 i s (Cχ_g)alkyl and R 15 is (C6_χQ)aryl(Co- g)alkyl, e.g. -S-CH 2 -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 13 in which X 4 is a direct bond, Rl3 is (C 1 . 6 )alkyl and R 15 is (C6-lθ)aryl(Cθ-6)alkyl, e.g. -S0 2 -CH 2 f , -S0 2 - oorr and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(c) in which: R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (i) (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or (ii) hetero(C 3 . 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl; R 5 is (C 6 -ι 0 )aryl(Co- 6 )alkyl, e.g. phenyl; X 7 is (i) -R 15 or -R 13 ' e.g. ( ~ or -CH=CH 2; respectively, (ϋ) -X 4 C(O)R 15 in which X 4 is a direct bond and Rl5 i s hetero(C3_ 1 o)cycloalkyl(Co_6)alkyl, e.g. -C (O) — N 0 , -C (0) — N > or -c (o) — N , (iii) -X 4 OR 15 in which X 4 is a direct bond and Rl5 is hetero(C3_χo')cycloalkyl(Co-6)alkyl, e.g. -o — ( o ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (C 1 _6)alkylene, R 13 is (C 1 . 6 )alkyl and R 15 is (C 6 . 10 )aryl(C 0 -6)alkyl, e.g. or -CH„ -S / ^ or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, Rl3 is (C!. 6 )alkyl and R 15 is (C 6 . 10 )aryl(C 0 .6)alkyl, e.g. . -SO 2 -CH 2 -CH=CH 2 , oorr and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Another particular group of compounds of the invention are compounds of formula 1(d): 1(d) wherein R 1 , R 2 and X 7 are as hereinbefore described, and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds of formula 1(d) and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Compounds of formula 1(d) in which R 1 is hydrogen and R 2 is: (xvi) hydrogen; (xvii) -X 4 OR 13 ' e.g. -CH 2 -O-CH 3 or -CH 2 -CH 2 -O-CH 3 ; (xviii) hetero(C 5 _ιo)aryl(Co- 6 )alkyl, e.g. thien-2-yl or 5-methylfuran-2-yl; (xix) (C 5 . 10 )aryl(Co. 6 )alkyl, e.g. phenethyl; (xx) (Cι„ 6 )alkyl, e.g. ethyl, n-propyl or n-butyl are preferred. Compounds of formula 1(d) in which R 1 and R 2 are both methyl are also preferred. Compounds of formula 1(d) in which R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or hetero(C 3 . 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl are also preferred. Compounds of formula 1(d) in which R 5 is (C 6 -ιo)aryl(Co- 6 )alkyl, e.g. phenyl are preferred. Compounds of formula 1(d) in which R 6 is hydrogen are preferred. Compounds of formula 1(a) in which X 7 is: (xvi) -R 15 or-R 13 e.g. or -CH=CH 2 ; (xvii) -X 4 C(O)R 15 in which X 4 is a direct bond and Rl5 i is hetero(C3_χo)cycloalkyl(Co_6)alkyl, e.g. -C (O) — N 0 , -c (0) — N ~~ λ > or -c (0) — N (xviii) -X 4 OR 15 in which X 4 is a direct bond and R 15 i is hetero(C3_ιo) c y c loalkyl(C()-6)alkyl, e.g. -o — ( o ; (xix) -X 4 SR 13 or-X 4 SR 15 in which X 4 is a direct bond or (C 1 _6)alkylene, R 13 is (Cι_6)alkyl and R .1 L 5 D is (C6_ιo)aryι( O-6) alk yl > e.g. -s-CH 2 (xx) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R 13 is (Cι_ 6 )al yl and R 15 is (C 6 . 10 )aryl(C 0 .6)alkyl, e.g. -SO 2 -CH 2 - -S0 2 -C / \ are preferred. Compounds of formula 1(c) in which X represents -c (0) — N 0 , -S-CH 2 — f y , -SO 2 -CH 2 — or are especially preferred. A preferred group of compounds of the invention are compounds of formula 1(d) in which: R 1 is hydrogen and R 2 is (i) hydrogen, (ii) X 4 OR 13 ' e.g. -CH 2 -O-CH 3 or -CH 2 -CH 2 -O-CH 3 , (iii) hetero(C 5 -ιo)aryl(Co- 6 )alkyl, e.g. thien-2-yl or 5-methylfuran-2-yl, (iv)(C 5 _ιo)aryl(Co. 6 )alkyl, e.g. phenethyl or (v) (Cι. 6 )alkyl, e.g. ethyl, n-propyl or n-butyl; R 5 is (C 6 _ιo)aryl(Co- 6 )alkyl, e.g. phenyl; R° is hydrogen; X7 is (i) -R 15 or -R 13 ' e.g. ( \ or -CH=CH 2) respectively ϋ -X 4 C(O)R 15 in which X 4 is a direct bond and R 13 ishetero(C3.ιo)cycloalkyl(Co-6)alkyl,e.g. -c (θ) — 0 , -C (0) — N > or -C (O) — N , (iii) -X 4 OR 15 in which X 4 is a direct bond and R* 5 is hetero(C3. 1 o)cycloalkyl(Co-6)alkyl, e.g. -o — ( 0 ; (iv) -X SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cι_6)alkyl, R 1 is (Cχ.6)alkyl and R 15 is (C6_io)aryl(Co-6) lkyl, or -CH,-S- or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, Rl3 is (C 1 . 6 )alkyl and R 15 is (C 6 . 10 )aryl(C 0 . 6 )alkyl, e.g. . ; and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(d) in which: R 1 and R 2 are both methyl; R 5 is (C 6 .ιo)aryl(Co- 6 )alkyl, e.g. phenyl; R6 is hydrogen; X' is (i) -R» « -*» ,_. ~Q or -CH=CH 2 , ( U ) -X W i, wMch X „ _ / \ direct bond and Rl5 is hetero(C3_χo) c ycloalkyl(Co-6)alkyl, e.g. -c (0) • N O \ / (iii) -X 4 OR 15 in which X 4 is a direct bond and R 15 is hetero(C3_ 10 )cycloalkyl(C 0 -6)alkyl, e.g. ; (iv) -X 4 SR 13 or-X 4 SR 15 in which X 4 is a direct bond or (Cχ_6)alkylene, R χ 3 J S (Cχ_6)alkyl andR 15 is (C6.χo) ar yi(Cθ- 6)alkyl, e.g. -S-CH 2 — ( , -S-CH 2 — f or -CH 2 -s — f y or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R 13 is (Cι_ 6 )alkyl and R 15 is ( 6-10)aryl(Co-6) al kyl e.g. -S0 2 -CH 2 f J , -S0 2 - - SO - — CH2 K / y or and their corresponding N-oxides, and F 3 C their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(d) in which: R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (i) (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or (ii) hetero(C 3 . 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl; R 5 is (C 6 -ιo)aryl(C 0 . 6 )alkyl, e.g. phenyl; R6 is hydrogen; X 7 is (i) -R 15 or -R 13, e.g. \ or -CH=CH 2 , (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and Rl5 is hetero(C3.χo) c ycloalkyl(Co_6)alkyl, e.g. C (O) — or -c (o) — N , (iii) -X 4 OR 15 in which X 4 is a direct bond and Rl5 i s hetero(C3_χo)cycloalkyl(Cθ-6)alkyl, e.g. -0 — ( 0 ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (C _6)alkylene, Rl3 is (Cχ. 6 )alkyl and R 15 is (C6_ o)aryl(Co-6)alkyl, e.g. -s-CH 2 — ( , -S-CH 2 — f y or -CH 2 -S — f or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, Rl3 is (C . 6 )alkyl and R 15 is (C 6 _ιo)aryl(C 0 -6)alkyl, e.g. . -SO 2 -CH 2 -CH=CH 2 , OoXr and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Another particular group of compounds of the invention are compounds of formula 1(e): 1(e) wherein R 1 , R 2 and X 7 are as hereinbefore described, and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds of formula 1(e) and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Compounds of formula 1(e) in which R 1 is hydrogen and R 2 is: (xxi) hydrogen; (xxii) -X 4 OR 13, e.g. -CH 2 -O-CH 3 or -CH 2 -CH 2 -O-CH 3 ; (xxiii) hetero(C 5 . 1 o)aryl(Co- 6 )alkyl, e.g. thien-2-yl or 5-methylfuran-2-yl; (xxiv) (C 5 _ιo)aryl(Co- 6 )alkyl, e.g. phenethyl; (xxv) (Cι_ 6 )alkyl, e.g. ethyl, n-propyl or n-butyl are preferred. Compounds of formula 1(e) in which R 1 and R 2 are both methyl are also preferred. Compounds of formula 1(e) in which R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or hetero(C 3 . 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl are also preferred. Compounds of formula 1(e) in which R and R are (Cι. )alkyl, e.g. methyl are preferred. Compounds of formula 1(a) in which X 7 is: (xxi) -R 15 or -R 13 ' e.g. / \ or -CH=CH 2> respectively". (xxii) -X 4 C(O)R 15 in which X 4 is a direct bond and R 15 i is hetero(C3_χo)cycloalkyl(Co-6)alkyl, e.g. -C (O) — N O . (xxiii) -X 4 OR 15 in which X 4 is a direct bond and R 15 is hetero(C3_ o) c y c io a ιkyl(Cθ- )alkyl, e.g. -o — ( 0 ; (xxiv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (C _6)alkylene, R 13 is (Cι_6)alkyl and R 15 is (Cg_ιo)aιyl(Co-6)alkyl, e.g. -s-CH 2 — ( , (xxv) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, Rl3 is (Cι_ 6 )alkyl and R 15 is (C 6 .ι 0 )aryl(C 0 -6)alkyl, e.g. -SO 2 -CH 2 - are preferred. Compounds of formula 1(e) in which X represents -c (0) —N r ~ \ 0 : , -S0 2 -CH 2 — f J or -so 2 -CH 2 — are especially F 2 HCO preferred. A preferred group of compounds of the invention are compounds of formula 1(e) in which: R 1 is hydrogen andR 2 is (i) hydrogen, (ii) X 4 OR 13 'e.g. -CH 2 -O-CH 3 or-CH 2 -CH 2 -O-CH 3 , (iii) hetero(C 5 _ιo)aryl(Co- 6 )alkyl, e.g. thien-2-yl or 5-methylfuran-2-yl, (iv)(C 5 . 10 )aryl(Co- 6 )alkyl, e.g. phenethyl or (v) (Cι. 6 )alkyl, e.g. ethyl, n-propyl or n-butyl; R 5 is (d. 4 )alkyl, e.g. methyl; X 7 is (i) -R 15 or -R 13 ' e.g. \ or -CH=CH 2 , (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and R 15 is hetero(C3.χo)cycloalkyl(Cθ-6)alkyl, e.g. -c (O) — 15 in which X 4 is a direct bond and Rl5 i s hetero(C3_χo) c y loalkyl(Co_6)alkyl, e.g. -o — ( O ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (C _ 6 )alkylene, Rl3 is (Cχ_ 6 )alkyl and R 15 is (C6_ 1 o)aryl(C 0 -6)alkyl, e.g. -S-CH 2 — <^ , -S-CH 2 — f y or -CH 2 -S 9 or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, Rl3 is (Cι_ 6 )alkyl and R 15 is (C 6 .ιo)aryl(C 0 .6)alkyl, e.g. . -SO 2 -CH 2 -CH=CH 2 , -CH 2 -S0 2 - / X -S0 2 -CH 2 - // W -S0 -CHr r- CN -SO„-C ooorrr ; and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(e) in which: R 1 and R 2 are both methyl; R 5 is (Cι. 4 )alkyl, e.g. methyl; X 7 is (i) -R 15 or -R 13 ' e.g. \ or -CH=CH 2 , (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and R 15 is hetero(C3_χo)cycloalkyl(Cθ-6)alkyl, e.g. -c (O) — 0 , -C (O) — > or -C (O) — N , (iii) -X 4 OR 15 in which X 4 is a direct bond and R 15 is hetero(C 3 _ 10 )cycloalkyl(C 0 -6)alkyl, e.g. -o — o ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cχ_6)alkylene, R*3 i s (Cχ_6)alkyl and R 15 is (C6_ o) ryl(Cθ- 6)al yl, e.g. -s-CH 2 — , -S-CH 2 — f or -CH 2 -S — or (v) -X 4 S(0) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond and R 13 is (C . 6 )alkyl and R 15 is (C 6 _ιo)aryl(C 0 -6)alkyl, e.g. . -SO 2 -CH 2 -CH=CH 2 , -S0 2 -CH 2 - // w o VrI and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(e) in which: R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (i) (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or (ii) hetero(C 3 . 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl; R 5 is (Cι. 4 )alkyl, e.g. methyl; X 7 is (i) - R 15 or-R 13 'e.g. \ or -CH=CH 2 , (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and Rl5 is hetero(C3_χo)cycloalkyl(Co-6)alkyl, e.g. -c (0) — N O , -C (O) — N > or -c ( O) — N , (iii) -X 4 OR 15 in which X 4 is a direct bond and Rl 5 is hetero(C3_ 10 )cycloalkyl(C 0 . 6 )alkyl, e.g. -o— 0 ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cχ_6)alkylene, R*3 i s (Cχ_6)alkyl and R 15 is (C6_ o) ar yi(Cθ- g)alkyl, e.g. -S-CH 2 ( , -S-CH 2 — or or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R 13 is (Ci _6)alkyl and R 15 is (C6-io) ar y 1 ( c o-6) alk yl e.g. - SO -CH If W / o o r r and their corresponding N-oxides, and F 3 C their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Another particular group of compounds of the invention are compounds of formula 1(f): 1(f) wherein R 1 , R 2 and X 7 are as hereinbefore described, and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds of formula 1(f) and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Compounds of formula 1(f) in which R 1 is hydrogen and R 2 is: (xxvi) hydrogen; (xxvii) -X 4 OR 13> e.g. -CH 2 -O-CH 3 or -CH 2 -CH 2 -O-CH 3 ; (xxviii) hetero(C 5 _ιo)aryl(Co.. 6 )alkyl, e.g. thien-2-yl or 5-methylfuran- 2-yl; (xxix) (C 5 . 10 )aryl(Co- 6 )alkyl, e.g. phenethyl; (xxx) (Cι. 6 )alkyl, e.g. ethyl, n-propyl or n-butyl are preferred. Compounds of formula 1(f) in which R 1 and R 2 are both methyl are also preferred. Compounds of formula 1(f) in which R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or hetero(C 3 . 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl are also preferred. Compounds of formula 1(f) in which R 5 is (C 6 -ι 0 )aryl(Co- 6 )alkyl, e.g. benzyl are preferred. Compounds of formula 1(f) in which R 6 is hydrogen are preferred. Compounds of formula 1(f) in which X 7 is: (xxvi) -R 15 or-R 13 'e.g. ( ) or -CH=CH ; (xxvii) -X 4 C(O)R 15 in which X 4 is a direct bond, R 15 is hetero(C3_χo)cycloalkyl(Co-6)alkyl, e.g. -c (O) — N O , -C ( O) — N Λ > or -c ( 0) — N A- (xxviii) -X 4 OR 15 in which X 4 is a direct bond and Rl5 i s hetero(C3_χo)cycloalkyl(Cθ-6)alkyl, e.g. -0 — ( O ; (xxix) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cι_6)al ylene, R 13 is (Cχ_6)alkyl and R 15 is (Ctø_ιo)aryl(C 6)alkyl, e.g. -s-CH (xxx) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R 1 is (Cι_ 6 )alkyl and R 15 is e.g. -SO 2 -CH 2 - are preferred. Compounds of formula 1(f) in which X represents -c (0) — N O , -S-CH 2 — / v/ W y , -SO 2 -CH 2 2 — f or - S02 - CH2 — sf are especially F 2 HCO preferred. A preferred group of compounds of the invention are compounds of formula 1(f) in which: R 1 is hydrogen and R 2 is (i) hydrogen, (ii) X 4 OR 13 ' e.g. -CH 2 -O-CH 3 or-CH 2 -CH 2 -O-CH 3 , (iii) hetero(C 5 „ιo)aryl(Co_ 6 )alkyl, e.g. thien-2-yl or 5-methylfuran-2-yl, (iv)(C 5 . 10 )aryl(C 0 . 6 )alkyl, e.g. phenethyl or (v) (Cι_ 6 )alkyl, e.g. ethyl, n-propyl or n-butyl; R 5 is (C 6 „ιo)aryl(Co- 6 )alkyl, e.g. benzyl; R 6 is hydrogen; X7 is (i) -R 15 or -R 13 ' e.g. or -CH=CH 2 , (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and Rl5 i is hetero(C3_χo)cycloalkyl(Cθ-6)alkyl, e.g. -c (0) — or -C (O) — N , (iii) -X 4 OR 15 in which X 4 is a direct bond and R 15 i is hetero(C3_io) c y clo aikyl(Co_6)alkyl, e.g. -o — ( 0 ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cχ_g)alkylene, R 13 i s (Cχ.g)alkyl and R 15 is (C6_ιo)aryl(Cθ- g)alkyl, e.g. -S-CH 2 — ( , -S-CH 2 — f y or -CH 2 -s — f y or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, Rl3 i s (C . 6 )alkyl and R 15 is (C6-10)aryl(C 0 -6)alkyl, e.g. -SO -CH / or ; and their corresponding N-oxides, and F 3 C their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(f) in which: R 1 and R 2 are both methyl; R 5 is (C 6 .ιo)aryl(Co- 6 )alkyl, e.g. benzyl; R 6 is hydrogen; X7 is (i) -R 15 or -R 13 ' e.g. / \ or -CH=CH 2 , (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and R 1 ^ is hetero(C3_χo)cycloalkyl(Cθ-6)alkyl, e.g. -c (O) — o, (iii) -X 4 OR 15 in which X 4 is a direct bond and Rl5 is hetero(C 3 . 10 )cycloalkyl(Co-6)alkyl, e.g. -o — I 0 ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cχ_6)alkylene, R i3 is (Cχ_6)alkyl and R 15 is (C6_χo)aryl(Cθ- 6) alk yl e.g. -S-C -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R*3 i s (C . 6 )alkyl and R 15 is (C 6 .io)aryl(C 0 .6)alkyl, e.g. -S0 2 -CH 2 f , oorr and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(f) in which: R 1 and R " taken together with the carbon atom to which both R 1 and R 2 are attached form (i) (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or (ii) hetero(C 3 . 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl; R 5 is (C 6 .ιo)aryl(C 0 . 6 )alkyl, e.g. benzyl; R° is hydrogen; X7 is (i) -R 13 or -R 1 *' e.g. (ii) -X 4 C(O)R ls in which X 4 is a direct bond and R 1 ^ is hetero(C3_χo) c y c l°alkyl(Co-6)alkyl, e.g. -C (O) — N 0 , -C (0) — N > or -C (0) — N , (iii) -X 4 OR 15 inwhichX 4 is a direct bond and R χ 5 is hetero(C3_χo)cycloalkyl(Co_6)alkyl, e.g. -o — ( 0 ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cχ_ 6 )alkyl, R 13 is (C . 6 )alkyl and R 15 is (C6_ιo)aιyl(Co_6)al yl, e.g. , -S-CH 2 — f or -CH 2 -S— f or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 13 in which X 4 is a direct bond, R 13 is (C^alkyl and R 15 is (C 6 . 10 )aryl(Co.6)alkyl, e.g. . -SO 2 -CH 2 -CH=CH 2 , -CH 2 -S0 2 - // -S0 2 -CH 2 // w -S0 2 -C and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Another particular group of compounds of the invention are compounds of formula 1(g): Kg) wherein R 1 , R 2 and X7 are as hereinbefore described, and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds of formula 1(g) and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Compounds of formula 1(g) in which R 1 is hydrogen and R 2 is: (xxxi) hydrogen; (xxxii) -X 4 OR 13 ' e.g. -CH 2 -O-CH 3 or -CH 2 -CH 2 -O-CH 3 ; (xxxiii) hetero(C 5 .ιo)aryl(C 0 - 6 )alkyl, e.g. thien-2-yl or 5-methylfuran- 2-yl; (xxxiv)(C 5 _ιo)aryl(Co- 6 )alkyl, e.g. phenethyl; (xxxv) (Cι. 6 )alkyl, e.g. ethyl, n-propyl or n-butyl are preferred. Compounds of formula 1(g) in which R 1 and R 2 are both methyl are also preferred. Compounds of formula 1(g) in which R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or hetero(C 3 . 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl are also preferred. Compounds of formula 1(g) in which X 3 is 2-methyl-4-oxo-tetrahydro-furan-3-yl, 2-ethyl-4-oxo-tetrahydro-furan-3-yl, 4-oxo-l-(l-phenyl-methanoyl)-pyrrolidin-3-yl or (S)-2-Acetoxy-4-oxo-azetidin-3-yl are preferred. Compounds of formula 1(g) in which X7 is: (xxxi) -R 10 or -R 13 , e.g. (xxxii) -X 4 C(O)R 15 in which X 4 is a direct bond and R 15 is hetero(C3_χo) c y c loalkyl(Co-6)alkyl, e.g. -C (O) — N O , (xxxiii) -X 4 OR 15 in which X 4 is a direct bond and R 15 is hetero(C3_χo)cycloalkyl(Co_6)alkyl, e.g. -O — ( 0 ; (xxxiv)-X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cχ_6)alkylene, R 13 i s (C _6)alkyl and R 15 is (C 6 . 10 )aryl(Co-6)alkyl, e.g. -s-CH 2 — , (xxxv) -X 4 S(O) 2 R 13 or -X S(O) 2 R 15 in which X 4 is a direct bond, Rl3 i s (C . 6 )alkyl and R 15 is (C 6 _ 10 )aryl(Cθ-6)alkyl, e.g. -SO 2 -CH 2 - -S0 2 -C are preferred. Compounds of formula 1(g) in which X7 represents -c (0) — 0 , o or r are especially preferred. A preferred group of compounds of the invention are compounds of formula 1(g) in which: R 1 is hydrogen and R 2 is (i) hydrogen, (ii) X 4 OR 13, e.g. -CH 2 -O-CH 3 or -CH 2 -CH 2 -O-CH 3 , (iii) hetero(C 5 -ιo)aryl(Co- 6 )alkyl, e.g. thien-2-yl or 5-methylfuran-2-yl, (iv)(C 5 .ιo)aryl(Co- 6 )alkyl, e.g. phenethyl or (v) (C 1 . 6 )alkyl, e.g. ethyl, n-propyl or n-butyl; X 3 is 2-methyl-4-oxo-tetrahydro-furan-3-yl, 2-ethyl-4-oxo-tetrahydro-furan-3-yl, 4-oxo-l-(l-phenyl-methanoyl)-pyrrolidin-3-yl or (S)-2-acetoxy-4-oxo-azetidin-3-yl; X7 is 0> -R. 5 OT - R » , g . -Q . ∞ ^ -^ R^ ^ ^ . dtoc. bond and R 1 is hetero(C3_χo)cycloalkyl(Co_6)alkyl, e.g. -C (O) — N O , , (iii) -X 4 OR 15 in which X 4 is a direct bond and R 15 is hetero(C 3 _ 10 )cycloalkyl(Co-6)alkyl, e.g. -o — ( 0 ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (Cι_g)alkylene, R χ 3 is (Cχ_6)alkyl and R 15 is (C6_ιo)a yi(Cθ- 6)alkyl, e.g. -s-CH 2 — ( , -S-CH 2 — y or or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, R χ 3 is (Cι_ 6 )alkyl and R 15 is (C6-10)aryl(C 0 -6)alkyl, e.g. . - -S0 2 -CH- W -S0 2 -CH -SO.-CH- -// or ; and their corresponding N-oxides, and F 3 C their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(g) in which: R 1 and R 2 are both methyl; X 3 is 2-methyl-4-oxo-tetrahydro-furan-3-yl, 2-ethyl-4-oxo-tetrahydro-furan-3-yl, 4-oxo-l-(l-phenyl-methanoyl)-pyrrolidin-3-yl or (S)-2-acetoxy-4-oxo-azetidin-3-yl; X7 is (i) -R 15 or -R 13 ' e.g. <^ \ or -CH=CH 2 , (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and R!5 is hetero(C3_ιo)cycloalkyl(Co- g)alkyl, e.g. -c ( o ) — N o , -c ( o ) — y or _c ( o ) — N , (iii) -X 4 OR 15 in which X 4 is a direct bond and R 1 ^ is hetero(C3_χo)cycloalkyl(C Q -6)alkyl, e.g. -o— ( 0 ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (C 1 . 6 )alkylene, Rl3 is (C 1 . 6 )alkyl and R 15 is (C 6 . 10 )aryl(C 0 -6)alkyl, e.g. , OΓ -CH 2 -S— f y or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, Rl3 is (C . 6 )alkyl and R 15 is (C 6 .ιo)aryl(C 0 -6)alkyl, e.g. . -SO 2 - o Orr and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. A further preferred group of compounds of the invention are compounds of formula 1(g) in which: R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (i) (C 3 . 8 )cycloalkylene, e.g. cyclopropyl or (ii) hetero(C 3 . 8 )cycloalkylene, e.g. tetrahydropyran-4-yl and N-methylpiperidin-4-yl; X 3 is 2-mexhyl-4-oxo-tetrahydro-furan-3-yl, 2-ethyl-4-oxo-tetrahydro-furan-3-yl, 4-oxo-l-(l-phenyl-methanoyl)-pyrrolidin-3-yl or (S)-2-Acetoxy-4-oxo-azetidin-3-yl; X 7 is (i) -R 15 or -R 13 ' e.g. / \ or -CH=CH 2 , (ii) -X 4 C(O)R 15 in which X 4 is a direct bond and R 1 ^ 1S hetero(C3_χo)cycloalkyl(Cθ-6)alkyl, e.g. -c (O) — N 0 , -c (0) — N y or -c (o) — N (iii) -X 4 OR 15 in which X 4 is a direct bond and R!5 is hetero(C 3 . 10 )cycloalkyl(Co-6)alkyl, e.g. -o— ( 0 ; (iv) -X 4 SR 13 or -X 4 SR 15 in which X 4 is a direct bond or (C .g)alkylene, R*3 i s (Cχ_6)alkyl and R 15 is (C6.χo) ryl(Cθ- g)alkyl, e.g. -S-CH 2 — , -S-CH 2 — or -CH 2 -S — or (v) -X 4 S(O) 2 R 13 or -X 4 S(O) 2 R 15 in which X 4 is a direct bond, Rl3 is (Cι_ 6 )alkyl and R 15 is (C6-10)aryl(C 0 -6)alkyl, e.g. . -SO 2 -CH 2 -CH=CH 2 , -CH 2 -SO_- f -S0 2 -C - SO - CH v/ W / o orr and their corresponding N-oxides, and F 3 C their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Reference to the preferred embodiments set forth above is meant to include all combinations of particular and preferred groups unless stated otherwise. Reference to the preferred embodiments set forth above is meant to include all combinations of particular and preferred groups. Particular compounds of the invention are selected from the compounds formed by: j oining the methylene carbon atom (CH 2 *) of one of the fragments (A 1 to A 116) shown in Table 1 to the carbon atom (*CH*) of one of the fragments (B 1 to B 115) shown in Table 2; j oining the carbon atom (* CH*) of one of the fragments (B 1 to B 115) shown in Table 2 to the acyl carbon atom (C*) of one of the fragments (Cl to C13) depicted in Table 3; and joining the methylene carbon atom (CH 2 *) of fragment Dl, the carbon atom (*CH*) of one of the fragments (C2, C6-C11 or C13) or the tertiary carbon atom (C*) of one of the fragments (C2-C5 or C12) depicted in Table 3 to the carbon atom (C*) of a cyano group, the acyl carbon atom (C*) of one of the fragments (D2-D6 or D8-D56) depicted in Table 4, the vinyl carbon atom (C*) of the fragment (D7) depicted in Table 4 or the acyl carbon atom (C*) of one of the fragments (E1-E14) depicted in Table 5. Particular compounds of formula 1(a) are selected from the compounds formed by: joining the methylene carbon atom (CH 2 *) of one of the fragments (Al to Al 16) shown in Table 1 to the carbon atom (*CH*) of one of the fragments (B 1 to B 115) shown in Table 2; joining the carbon atom (*CH*) of one of the fragments (Bl toB115) shown in Table 2 to the acyl carbon atom (C*) of one of the fragments (Cl to C13) depicted in Table 3; and joining the methylene carbon atom (CH 2 *) of fragmentDl, the carbon atom (*CH*) of one of the fragments (C2, C6-C11 or C13) or the tertiary carbon atom (C*) of one of the fragments (C2-C5 or C12) depicted in Table 3 to the carbon atom (C*) of a cyano group depicted in Table 4. Particular compounds of formula (lb) are selected from the compounds formed by: j oining the methylene carbon atom (CH 2 *) of one of the fragments (A 1 to A 116) shown in Table 1 to the carbon atom (*CH*) of one of the fragments (B 1 to B 115) shown in Table 2; joining the carbon atom (*CH*) of one of the fragments (B 1 to B 115) shown in Table 2 to the acyl carbon atom (C*) of one of the fragments(Cl to C13) depicted in Table 3; and joining the methylene carbon atom (CH 2 *) of fragmentDl, the carbon atom (*CH*) of one of the fragments (C2, C6-C11 or C13) or the tertiary carbon atom (C*) of one of the fragments (C2-C5 or C12) depicted in Table 3 to the acyl carbon atom (C*) of one of the fragments (D2, D4-D6, D9-D11, D18-D24, D45-D46 or D48-D56) depicted in Table 4. Particular compounds of formula 1(c) are selected from the compounds formed by: joining the methylene carbon atom (CH 2 *) of one of the fragments (Al to Al 16) shown in Table 1 to the carbon atom (* CH*) of one of the fragments (B 1 to B 115) shown in Table 2; j oining the carbon atom (*CH*) of one of the fragments (B 1 to B 115) shown in Table 2 to the acyl carbon atom (C*) of one of the fragments(Cl to C13) depicted in Table 3; and joining the methylene carbon atom (CH 2 *) of fragmentDl, the carbon atom (*CH*) of one of the fragments (C2, C6-C11 or C13) or the tertiary carbon atom (C*) of one of the fragments (C2-C5 or C12) depicted in Table 3 to the vinyl carbon atom (C*) of the fragment (D7) depicted in Table 4. Particular compounds of formula 1(d) are selected from the compounds formed by: joining the methylene carbon atom (CH 2 *) of one of the fragments (Al to Al 16) shown in Table 1 to the carbon atom (*CH*) of one of the fragments (Bl to B115) shown in Table 2; joining the carbon atom (*CH*) of one of the fragments (B 1 to B 115) shown in Table 2 to the acyl carbon atom (C*) of one of the fragments(Cl to C13) depicted in Table 3; and joining the methylene carbon atom (CH 2 *) of fragment Dl, the carbon atom (*CH*) of one of the fragments (C2, C6-C11 or C13) or the tertiary carbon atom (C*) of one of the fragments (C2-C5 or C 12) depicted in Table 3 to the acyl carbon atom (C*) of the fragment (D17) depicted in Table 4. Particular compounds of formula 1(e) are selected from the compounds formed by: joining the methylene carbon atom (CH 2 *) of one of the fragments (Al to Al 16) shown in Table 1 to the carbon atom (*CH*) of one of the fragments (Bl to Bl 15) shown in Table 2; joining the carbon atom (*CH*) of one of the fragments (Bl toB115) shown in Table 2 to the acyl carbon atom (C*) of one of the fragments(Cl to C13) depicted in Table 3; and joining the methylene carbon atom (CH 2 *) of fragment Dl, the carbon atom (*CH*) of one of the fragments (C2, C6-C11 or C13) or the tertiary carbon atom (C*) of one of the fragments (C2-C5 or C 12) depicted in Table 3 to the acyl carbon atom (C*) of the fragment (D15) depicted in Table 4. Particular compounds of formula 1(f) are selected from the compounds formed by: joining the methylene carbon atom (CH 2 *) of one of the fragments (Al to Al 16) shown in Table 1 to the carbon atom (* CH*) of one of the fragments (B 1 to B 115) shown in Table 2; joining the carbon atom (*CH*) of one of the fragments (Bl to Bl 15) shown in Table 2 to the acyl carbon atom (C*) of one of the fragments(Cl to C13) depicted in Table 3; and joining the methylene carbon atom (CH 2 *) of fragmentDl, the carbon atom (*CH*) of one of the fragments (C2, C6-C11 or C13) or the tertiary carbon atom (C*) of one of the fragments (C2-C5 or C12) depicted in Table 3 to the acyl carbon atom (C*) of one of the fragments (D8, D25-D44) depicted in Table 4. Particular compounds of formula 1(g) are selected from the compounds formed by: joining the methylene carbon atom (CH 2 *) of one of the fragments (Al to Al 16) shown in Table 1 to the carbon atom (*CH*) of one of the fragments (B 1 to B 115) shown in Table 2; joining the carbon atom (*CH*) of one of the fragments (Bl to Bl 15) shown in Table 2 to the acyl carbon atom (C*) of one of the fragments(Cl to C13) depicted in Table 3; and joining the methylene carbon atom (CH 2 *) of fragmentDl, the carbon atom (*CH*) of one of the fragments (C2, C6-C11 or C13) or the tertiary carbon atom (C*) of one of the fragments (C2-C5 or C12) depicted in Table 3 to the acyl carbon atom (C*) of one of the fragments (El -El 4) depicted in Table 5. TABLE 1 TABLE 2 TABLE 3 TABLE 4 TABLE 5 Particularly preferred compounds of "A", "B", "C" and "D" or "A", "B" and "E" combinations are illustrated in table 6: o 90 © CN N N N N N N N N N N Λ Q Λ Q Λ Λ Λ N N N Λ Q Λ Q Λ Q Q N N M Q Q Q Q Q Q n N Cl N P P P P P P p cN N Q N N N P Q P P P P P P P P ' ' i ' i i ' P P P ' ι ι ι i ' P P P ι i ' i ' i ι P Q P o ^ I I I I I I ~ I CN CN CN CN CN N W " " ^ CN CN C N N " " " CN C < M CN ' P . P i P I U U ϋ U U O U N t CΛ n N N N CJ U J, ,i i i i i i i i C CJ ' CJ U U i CJ i CJ i O i CJ i U i U i CJ i i U I C '4 CN ' CN ■ CN ■ CN CN • CN > CJ i U i U i O >s O ' O 's O 'S O 's O 's O 'S O i U U V 'I V , 'I i ,ni , IOi VI , O ' IO ' U U U co co co co co co co i i SO so so m n tn n vi vi i '* '* '* m in in in m i in σs os H pg so so so p PQ pq pq pq pq pq co co co pq cQ pa pq pq pq pq co co co pq pq pq q Q Q Q ^ ^ ^ p pq pq pq pq >n vi in pq pq pq pq pq pq pq r- r- U ' n w w i i i i pq cQ CQ i • i i i i i pq PQ pq i i i i cQ oq CO "tf Os r^ os i vo i i i -^t os α. <<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<<< A9-B79-C2-D2 A39-B89-C2-D2 A9-B39-C3-D2 A39-B85-C3-D2 A13-B79-C2-D2 A65-B89-C2-D2 A13-B39-C3-D2 A65-B85-C3-D2 A24-B79-C2-D2 A66-B89-C2-D2 A24-B39-C3-D2 A66-B85-C3-D2 A69-B79-C2-D2 A2-B92-C2-D2 A69-B39-C3-D2 A2-B86-C3-D2 A67-B79-C2-D2 60 A3-B92-C2-D2 115 A67-B39-C3-D2 170 A3-B86-C3-D2 A39-B79-C2-D2 A9-B92-C2-D2 A39-B39-C3-D2 A9-B86-C3-D2 A65-B79-C2-D2 A13-B92-C2-D2 A65-B39-C3-D2 . A13-B86-C3-D2 A66-B79-C2-D2 A24-B92-C2-D2 A66-B39-C3-D2 A24-B86-C3-D2 A2-B80-C2-D2 A69-B92-C2-D2 A2-B45-C3-D2 A69-B86-C3-D2 A3-B80-C2-D2 65 A67-B92-C2-D2 120 A3-B45-C3-D2 175 A67-B86-C3-D2 A9-B80-C2-D2 A39-B92-C2-D2 A9-B45-C3-D2 A39-B86-C3-D2 A13-B80-C2-D2 A65-B92-C2-D2 A13-B45-C3-D2 A65-B86-C3-D2 A24-B80-C2-D2 A66-B92-C2-D2 A24-B45-C3-D2 A66-B86-C3-D2 A69-B80-C2-D2 A2-B4-C3-D2 A69-B45-C3-D2 A2-B87-C3-D2 A67-B80-C2-D2 70 A3-B4-C3-D2 125 A67-B45-C3-D2 180 A3-B87-C3-D2 A39-B80-C2-D2 A9-B4-C3-D2 A39-B45-C3-D2 A9-B87-C3-D2 A65-B80-C2-D2 A13-B4-C3-D2 A65-B45-C3-D2 A13-B87-C3-D2 A66-B80-C2-D2 A24-B4-C3-D2 A66-B45-C3-D2 A24-B87-C3-D2 A2-B85-C2-D2 A69-B4-C3-D2 A2-B53-C3-D2 A69-B87-C3-D2 A3-B85-C2-D2 75 A67-B4-C3-D2 130 A3-B53-C3-D2 185 A67-B87-C3-D2 A9-B85-C2-D2 A39-B4-C3-D2 A9-B53-C3-D2 A39-B87-C3-D2 A13-B85-C2-D2 A65-B4-C3-D2 A13-B53-C3-D2 A65-B87-C3-D2 A24-B85-C2-D2 A66-B4-C3-D2 A24-B53-C3-D2 A66-B87-C3-D2 A69-B85-C2-D2 A2-B5-C3-D2 A69-B53-C3-D2 A2-B89-C3-D2 A67-B85-C2-D2 80 A3-B5-C3-D2 135 A67-B53-C3-D2 190 A3-B89-C3-D2 A39-B85-C2-D2 A9-B5-C3-D2 A39-B53-C3-D2 A9-B89-C3-D2 A65-B85-C2-D2 A13-B5-C3-D2 A65-B53-C3-D2 A13-B89-C3-D2 A66-B85-C2-D2 A24-B5-C3-D2 A66-B53-C3-D2 A24-B89-C3-D2 A2-B86-C2-D2 A69-B5-C3-D2 A2-B79-C3-D2 A69-B89-C3-D2 A3-B86-C2-D2 85 A67-B5-C3-D2 140 A3-B79-C3-D2 195 A67-B89-C3-D2 A9-B86-C2-D2 A39-B5-C3-D2 A9-B79-C3-D2 A39-B89-C3-D2 A13-B86-C2-D2 A65-B5-C3-D2 A13-B79-C3-D2 A65-B89-C3-D2 A24-B86-C2-D2 A66-B5-C3-D2 A24-B79-C3-D2 A66-B89-C3-D2 A69-B86-C2-D2 A2-B6-C3-D2 A69-B79-C3-D2 A2-B92-C3-D2 A67-B86-C2-D2 90 A3-B6-C3-D2 145 A67-B79-C3-D2 200 A3-B92-C3-D2 A39-B86-C2-D2 A9-B6-C3-D2 A39-B79-C3-D2 A9-B92-C3-D2 A65-B86-C2-D2 A13-B6-C3-D2 A65-B79-C3-D2 A13-B92-C3-D2 A66-B86-C2-D2 A24-B6-C3-D2 A66-B79-C3-D2 A24-B92-C3-D2 A2-B87-C2-D2 A69-B6-C3-D2 A2-B80-C3-D2 A69-B92-C3-D2 A3-B87-C2-D2 95 A67-B6-C3-D2 150 A3-B80-C3-D2 205 A67-B92-C3-D2 A9-B87-C2-D2 A39-B6-C3-D2 A9-B80-C3-D2 A39-B92-C3-D2 A13-B87-C2-D2 A65-B6-C3-D2 A13-B80-C3-D2 A65-B92-C3-D2 A24-B87-C2-D2 . A66-B6-C3-D2 A24-B80-C3-D2 A66-B92-C3-D2 A69-B87-C2-D2 A2-B32-C3-D2 A69-B80-C3-D2 A2-B4-C4-D2 A67-B87-C2-D2 100 A3-B32-C3-D2 155 A67-B80-C3-D2 210 A3-B4-C4-D2 A39-B87-C2-D2 A9-B32-C3-D2 A39-B80-C3-D2 A9-B4-C4-D2 A65-B87-C2-D2 A13-B32-C3-D2 A65-B80-C3-D2 A13-B4-C4-D2 A66-B87-C2-D2 A24-B32-C3-D2 A66-B80-C3-D2 A24-B4-C4-D2 A2-B89-C2-D2 A69-B32-C3-D2 A2-B85-C3-D2 A69-B4-C4-D2 A3-B89-C2-D2 105 A67-B32-C3-D2 160 A3-B85-C3-D2 215 A67-B4-C4-D2 A9-B89-C2-D2 A39-B32-C3-D2 A9-B85-C3-D2 A39-B4-C4-D2 A13-B89-C2-D2 A65-B32-C3-D2 A13-B85-C3-D2 A65-B4-C4-D2 A24-B89-C2-D2 A66-B32-C3-D2 A24-B85-C3-D2 A66-B4-C4-D2 A69-B89-C2-D2 A2-B39-C3-D2 A69-B85-C3-D2 A2-B5-C4-D2 A67-B89-C2-D2 110 A3-B39-C3-D2 165 A67-B85-C3-D2 220 A3-B5-C4-D2 A9-B5-C4-D2 A39-B53-C4-D2 A9-B89-C4-D2 A39-B32-C5-D2 A13-B5-C4-D2 A65-B53-C4-D2 A13-B89-C4-D2 A65-B32-C5-D2 A24-B5-C4-D2 A66-B53-C4-D2 A24-B89-C4-D2 A66-B32-C5-D2 A69-B5-C4-D2 A2-B79-C4-D2 A69-B89-C4-D2 A2-B39-C5-D2 A67-B5-C4-D2 60 A3-B79-C4-D2 115 A67-B89-C4-D2 170 A3-B39-C5-D2 A39-B5-C4-D2 A9-B79-C4-D2 A39-B89-C4-D2 A9-B39-C5-D2 A65-B5-C4-D2 A13-B79-C4-D2 A65-B89-C4-D2 A13-B39-C5-D2 A66-B5-C4-D2 A24-B79-C4-D2 A66-B89-C4-D2 A24-B39-C5-D2 A2-B6-C4-D2 A69-B79-C4-D2 A2-B92-C4-D2 A69-B39-C5-D2 A3-B6-C4-D2 65 A67-B79-C4-D2 120 A3-B92-C4-D2 175 A67-B39-C5-D2 A9-B6-C4-D2 A39-B79-C4-D2 A9-B92-C4-D2 A39-B39-C5-D2 A13-B6-C4-D2 A65-B79-C4-D2 A13-B92-C4-D2 A65-B39-C5-D2 A24-B6-C4-D2 A66-B79-C4-D2 A24-B92-C4-D2 A66-B39-C5-D2 A69-B6-C4-D2 A2-B80-C4-D2 A69-B92-C4-D2 A2-B45-C5-D2 A67-B6-C4-D2 70 A3-B80-C4-D2 125 A67-B92-C4-D2 180 A3-B45-C5-D2 A39-B6-C4-D2 A9-B80-C4-D2 A39-B92-C4-D2 A9-B45-C5-D2 A65-B6-C4-D2 A13-B80-C4-D2 A65-B92-C4-D2 A13-B45-C5-D2 A66-B6-C4-D2 A24-B80-C4-D2 A66-B92-C4-D2 A24-B45-C5-D2 A2-B32-C4-D2 A69-B80-C4-D2 A2-B4-C5-D2 A69-B45-C5-D2 A3-B32-C4-D2 75 A67-B80-C4-D2 130 A3-B4-C5-D2 185 A67-B45-C5-D2 A9-B32-C4-D2 A39-B80-C4-D2 A9-B4-C5-D2 A39-B45-C5-D2 A13-B32-C4-D2 A65-B80-C4-D2 A13-B4-C5-D2 A65-B45-C5-D2 A24-B32-C4-D2 A66-B80-C4-D2 A24-B4-C5-D2 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A24-B45-C3-D13 A66-B86-C3-D13 A69-B80-C2-D13 A2-B4-C3-D13 A69-B45-C3-D13 A2-B87-C3-D13 A67-B80-C2-D13 70 A3-B4-C3-D13 125 A67-B45-C3-D13 180 A3-B87-C3-D13 A39-B80-C2-D13 A9-B4-C3-D13 A39-B45-C3-D13 A9-B87-C3-D13 A65-B80-C2-D13 A13-B4-C3-D13 A65-B45-C3-D13 A13-B87-C3-D13 A66-B80-C2-D13 A24-B4-C3-D13 A66-B45-C3-D13 A24-B87-C3-D13 A2-B85-C2-D13 A69-B4-C3-D13 A2-B53-C3-D13 A69-B87-C3-D13 A3-B85-C2-D13 75 A67-B4-C3-D13 130 A3-B53-C3-D13 185 A67-B87-C3-D13 A9-B85-C2-D13 A39-B4-C3-D13 A9-B53-C3-D13 A39-B87-C3-D13 A13-B85-C2-D13 A65-B4-C3-D13 A13-B53-C3-D13 A65-B87-C3-D13 A24-B85-C2-D13 A66-B4-C3-D13 A24-B53-C3-D13 A66-B87-C3-D13 A69-B85-C2-D13 A2-B5-C3-D13 A69-B53-C3-D13 A2-B89-C3-D13 A67-B85-C2-D13 80 A3-B5-C3-D13 135 A67-B53-C3-D13 190 A3-B89-C3-D13 A39-B85-C2-D13 A9-B5-C3-D13 A39-B53-C3-D13 A9-B89-C3-D13 A65-B85-C2-D13 A13-B5-C3-D13 A65-B53-C3-D13 A13-B89-C3-D13 A66-B85-C2-D13 A24-B5-C3-D13 A66-B53-C3-D13 A24-B89-C3-D13 A2-B86-C2-D13 A69-B5-C3-D13 A2-B79-C3-D13 A69-B89-C3-D13 A3-B86-C2-D13 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3-biphenyl-4-yl-N-cyanomethyl-2-benzylsulfonylmethyl-propionamide; 3-(3-bromo-phenyl)-N-cyanomethyl-2-benzylsulfonylmethyl-propionamide; N-cyanomeΛyl-3-(3-cyano-benzylsulfonyl)-2-benzylsulfonyl-methyl-propionamide; N-cyanomethyl-2-[2-l,l-difluoro-methoxy)-benzylsulfanylmethyl]-3-benzylsulfanyl- propionamide; N-cyanomethyl-3-(2-trifluoromethyl-benzylsulfanyl)-2-(2-trifluoro-methyl- benzylsulfanylmethyl)-propionamide; N-cyanomethyl-3-isobutylsulfanyl-2-isobutylsulfanylmethyl-propionamide; N-cyanomethyl-4-phenylsulfanyl-2-(2-phenylsulfanyl-ethyl)-butyramide; N-cyanomethyl-3-[2-(l,l-cUfluoro-memoxy)-benzylsulfanyl]-2-[2-(l,l-difluoro-methoxy)- benzylsulfanylmethyl]-propionamide; 3-benzylsulfanyl-2-benzylsulfanylmethyl-N-cyanomethyl-propionamide; N-cyanomethyl-2- [2-1,1 -difluoro-methoxy)-benzylsulf onylmethyl] -3-benzylsulf onyl- propionamide; N-cyanomethyl-3-(2-trifluoromethyl-benzylsulfonyl)-2-(2-trifluoromethyl- benzylsulfonylmethyl)-propionamide; 4-benzenesulfonyl-2-(2-benzenesulfonyl-emyl)-N-cyanomemyl-butyramide; N-cyanomethyl-3-[2-( 1 , 1 -difluoro-me thoxy)-benzylsulfonyl] -2-[2-( 1 , 1 -difluor o-methoxy)- benzylsulfonylmethyl]-propionamide; N-cyanomethyl-3-benzylsulfonyl-2-benzylsulfonylmethyl-propionamide; N-cyanomethyl-3-(2-methyl-pr opane- 1 -sulfonyl)-2-(2-methyl-propane- 1 -sulf onylmethyl)- propionamide; N-cyanomethyl-3-(2-methyl-thiazol-4-ylmethylsulfonyl)-2-benzyl-sulfonylmethyl- propionamide; 3-biphenyl-3-yl-N-cyanomethyl-2-[2-(l,l-difluoro-methoxy)-benzyl-sulfonylmethyl]- propionamide; (3 '- { 2-(cyanomethyl-carbamoyl)-3- [2-( 1 , 1 -difluoro-methoxy)-benzyl-sulf onyl] -propyl } - biphenyl-4-yl)-carba_nic acid ethyl ester; N-cyanomethyl-2-[2-(l,l-difluoro-methoxy)-benzylsulfonylmethyl]-3-(4'- methylsulf onylamino-biphenyl-3-yl)-propionamide; 3-(3-bromo-phenyl)-N-cyanomethyl-2-[2-(l , 1 -difluoro-me thoxy)-phenyl- methylsulfonylmethylj-propionamide; N-cyanomethyl-2-((E)-3-phenyl-allyl)-3-benzylsulfonyl-propionamide; N-cyanomethyl-3-benzylsulfonyl-2-(3-phenyl-propyl)-propionamide; N-[(S)-l-(l-Benzooxazol-2-yl-methanoyl)-buryl]-3-benzylsulfonyl-2- benzylsulfonylmethyl-propionamide; N-[(S)-l-(l-Benzooxazol-2-yl-met_ιanoyl)-butyl]-3-(2-trifluorometτιyl-benzylsulfonyl)-2- (2-1rifluoromethyl-benzylsulfonylmethyl)-propionarnide; N-[(S)-l-(l-Benzooxazol-2-yl-methanoyl)-pentyl]-4-(2-methoxy-benzenesulfonyl)-2-[2-(2- methoxy-benzenesulfonyl)-ethyl]-butyramide; 4-Benzenesulfonyl-2-(2-benzenesulfonyl-ethyl)-N-[(S)-l-(l-ber_zooxazol-2-yl-methanoyl)- butylj-butyramide; (R)-N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-butyl]-2-cyclohexylmethyl-3- benzylsulfonyl-propionamide; N-[(S)-l-(l-benzothiazol-2-yl-methanoyl)-propyl]-4-morpholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide; N- [(S)- 1 -( 1 -benzooxazol-2-yl-methanoyl)-butyl] -3-cyclohexyl-2-cyclohexylmethyl- propionamide; N-[(S)-l-(l-Benzooxazol-2-yl-methanoyl)-butyl]-3-isobutylsulfanyl-2- isobutylsulfanylmethyl-propionamide; N-[(S)-l-(l-benzooxazol-2-yl-memanoyl)-butyl]-3-benzylsulfanyl-2-benzylsulfanylmethyl- propionamide; N- [(S)- 1 -( l-benzooxazol-2-yl-methanoyl)-bu tyl] -4-phenylsulfanyl-2-(2-phenylsulf anyl- ethyl)-butyramide; N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-propyl]-4-morpholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide; N- [(S)- 1 -( 1 -Benzooxazol-2-yl-methanoyl)-pen tyl] -4-morpholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide; 4-Mo holin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-{(S)-l-[l-(3-phenyl-[l,2,4]oxadiazol- 5-yl)-methanoyl]-propyl}-butyramide; N-[(S)-l-(l-Benzooxazol-2-yl-methanoyl)-butyl]-2-[2-(l,l-difluoro-methoxy)- benzylsulfonylmethyl]-3-benzylsulfonyl-propionamide; 4-Morpholin-4-yl-4-oxo-N-[l-(2-oxo-2-phenyl-acetyl)-pentyl]-2-benzylsulfonylmethyl- butyramide; N-(l,l-Dimethyl-2-oxazolo[4,5-b]pyridin-2-yl-2-oxo-ethyl)-4-morpholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide; N-[l-(5-Ethyl-[l,3,4]oxadiazole-2-carbonyl)-butyl]-4-morpholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide; N- [ 1 -(5-Ethyl- [1,3 ,4]oxadiazole-2-carbonyl)-butyl]-4-oxo-2-benzylsulfonyl-methyl-4- piperidin- 1 -yl-butyramide; N-[l-(5-Ethyl-[l,3,4]oxadiazole-2-carbonyl)-butyl]-4-oxo-2-benzylsulfonyl-methyl-4- pyrrolidin- 1 -yl-butyramide; N-[l-(5-Methoxymethyl-[l,3,4]oxadiazole-2-carbonyl)-propyl]-4-moφholin-4-yl-4-oxo-2- benzylsixlfonylmethyl-butyramide; N-[l-(5-Methoxymethyl-[l,3,4]oxadiazole-2-carbonyl)-propyl]-4-oxo-2- benzylsulfonylmethyl-4-piperidin- 1 -yl-butyramide; N-[l-(5-Methoxymethyl-[l,3,4]oxadiazole-2-carbonyl)-propyl]-4-oxo-2- benzylsulfonylmethyl-4-pyrrolidin- 1 -yl-butyramide; 4-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-[l-(5-phenyl-[l,3,4]oxadiazole-2- carbonyl)-propyl]-butyramide; 4-Oxo-2-benzylsulfonylmethyl-N-[l-(5-phenyl-[l,3,4]oxadiazole-2-carbonyl)-propyl]-4- piperidin- 1 -yl-butyramide; 4-Oxo-2-benzylsulf onylmethyl-N-[ 1 -(5 -phenyl-[ 1 ,3,4] oxadiazole-2-carbonyl)-propyl] -4- pyrrolidin- 1 -yl-butyramide; 4-Morpholin-4-yl-N-[l-(oxazolo[4,5-b]pyridine-2-carbonyl)-propyl]-4-oxo-2- benzylsulfonylmethyl-butyramide; N-[l-(Oxazolo[4,5-b]pyridine-2-carbonyl)-propyl]-4-oxo-2-benzylsulfonyl-methyl-4- piperidin- 1 -yl-butyramide; N-[l-(Oxazolo[4,5-b]pyridine-2-carbonyl)-propyl]-4-oxo-2-benzylsulfonyl-methyl-4- pyrrolidin-1 -yl-butyramide; 4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-[l-(5-pyridin-4-yl-[l,3,4]oxadiazole-2- carbonyl)-propyl] -butyramide; 4-Oxo-2-benzylsulfonylmethyl-4-piperidin-l-yl-N-[l-(5-pyridin-4-yl-[l,3,4]oxadiazole-2- carbonyl)-propyl] -butyramide; 4-Oxo-2-benzylsulfonylmethyl-N-[l-(5-pyridin-4-yl-[l,3,4]oxadiazole-2-carbonyl)- propyl] -4-pyrrolidin- 1 -yl-butyramide; 4-Mo holin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-[l-(5-pyridin-3-yl-[l,3,4]oxadiazole-2- carbonyl)-propyl] -butyramide; N-[l-(Benzooxazole-2-carbonyl)-propyl]-4-oxo-2-benzylsulfonylmethyl-4-piperidin-l-yl- butyramide; N-[l-(Benzooxazole-2-carbonyl)-propyl]-4-oxo-2-benzylsulfonylmethyl-4-pyrrolidin-l-yl- butyramide; N-[l-(Benzooxazole-2-carbonyl)-propyl]-2-cyclohexylmethyl-4-moφholin-4-yl-4-oxo- butyramide; 2-Cyclohexylmethyl-4-moφholin-4-yl-N-[l-(oxazolo[4,5-b]pyridine-2-carbonyl)-propyl]- 4-oxo-butyramide; 2-Cyclohexylmethyl-Ν-[l-(5-ethyl-[l,3,4]oxadiazole-2-carbonyl)-butyl]-4-moφholin-4-yl- 4-oxo-butyramide; N-(2-Benzooxazol-2-yl-l-methoxymethyl-2-oxo-ethyl)-2-(2-difluoromethoxy- benzylsulfonylmethyl)-4-moφholin-4-yl-4-oxo-butyramide; N-[l-(Benzooxazole-2-carbonyl)-propyl]-2-(2-cyclohexyl-ethyl)-4-moφholin-4-yl-4-oxo- butyramide; 2-(2-Cyclohexyl-ethyl)-4-moφholin-4-yl-N-[l-(oxazolo[4,5-b]pyridine-2-carbonyl)- propyl]-4-oxo-butyramide; 2-(2-Cyclohexyl-ethyl)-4-moφholin-4-yl-4-oxo-N-[ 1 -(5-phenyl- [ 1 ,3 ,4] oxadiazole-2- carbonyl)-propyl]-butyramide; 2-(2-Difluoromethoxy-benzylsulfonylmethyl)-4-moφholin-4-yl-4-oxo-N-[l-(5-phenyl- [l,3,4]oxadiazole-2-carbonyl)-propyl]-butyramide; 2-(2-Difluoromethoxy-benzylsulfonylmethyl)-N-[l-(5-ethyl-[l,3,4]oxadiazole-2-carbonyl)- butyl]-4-moφholin-4-yl-4-oxo-butyramide; N-[l-(Benzooxazole-2-carbonyl)-propyl]-2-(2-di_luoromethoxy-benzyl-sulfonylmethyl)-4- moφholin-4-yl-4-oxo-butyramide; 2-(2-Moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, l-(benzooxazole-2-carbonyl)-propyl]-amide; (R)-2-Cyclohexyhnethyl-4-moφholin-4-yl-4-oxo-N-[(S)-l-(5-phenyl-l,2,4-oxadiazole-3- carbonyl)-propyl] -butyramide; 2-(2-Moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, (S)-l-(5-phenyl-[l,2,4]oxadiazole-3-carbonyl)-propyl]-amide; 4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-[(S)-l-(5-phenyl-l,2,4-oxadiazole-3- carbonyl)-propyl] -butyramide; (R)-2-Cyclohexylmethyl-4-moφholin-4-yl-4-oxo-N-[(S)-l-(3-phenyl-l,2,4-oxadiazole-5- carbonyl)-propyl]-butyramide; 4-Moφholin-4-yl-N- [ 1 -(oxazole-2-carbonyl)-3 -phenyl-propyl] -4-oxo-2- benzylsulfonylmethyl-butyramide; N-(l , 1 -Dime thyl-2-oxazol-2-yl-2-oxo-ethyl)-4-moφholm-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide; N-4-Isopropyl-N- 1 - [ 1 -(oxazole-2-carbonyl)-3 -phenyl-propyl] -2-benzylsulf onylmethyl- succinamide; 2-(2-Difluoromethoxy-benzylsulfonylmethyl)-4-moφholin-4-yl-N-[l-(oxazole-2- carbonyl)-3-phenyl-propyl]-4-oxo-butyramide; 2-(2-Methyl-propane-l-sulfonylmethyl)-4-moφholin-4-yl-N-[l-(oxazole-2-carbonyl)-3- phenyl-propyl]-4-oxo-butyramide; 2-Cyclopropylmethylsulfonylmethyl-4-moφholin-4-yl-N-[l-(oxazole-2-carbonyl)-3- phenyl-propyl]-4-oxo-butyramide; N-[l-(Benzooxazole-2-carbonyl)-butyl]-2-benzylsulfonyl-3-(tetrahydro-pyran-4- yloxymethyl)-propionamide; N-[l-(Benzooxazole-2-carbonyl)-butyl]-3-ethanesulfonyl-2-(tetrahydro-pyran-4- yloxymethyl)-propionamide; N-(l-Benzenesulfonyl-3-oxo-azepan-4-yl)-2-cyclopropylmethylsulfonyl-methyl-4- moφholin-4-yl-4-oxo-butyramide; 2-Cyclopropylme thylsulfonylmethyl-Ν- { (S)- 1 -[(R)-hydroxy-(3-phenyl- 1 ,2,4-oxadiazol-5- yl)-methyl] -propyl } -4-moφholin-4-yl-4-oxo-butyramide; N-{(S)-l-[(R)-hydroxy-(3-phenyl-l,2,4-oxadiazol-5-yl)-methyl]-propyl}-2-(2-methyl- propane- 1 -sulfonylmethyl)-4-moφholin-4-yl-4-oxo-butyramide; 2-(2-Moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoicacid {(S)-l-[(R)-hydroxy-(3-phenyl- 1 ,2,4-oxadiazol-5 -yl)-methyl] -propyl } -amide; 2-Cyclopropylmethylsulfonylmethyl-4-moφholin-4-yl-4-oxo-Ν-[(S)-l-(3-phenyl-l,2,4- oxadiazole-5-carbonyl)-propyl]-butyramide; 2-(2-methyl-propane-l-sulfonylmethyl)-4-moφholin-4-yl-4-oxo-N-[(S)-l-(3-phenyl-l,2,4- oxadiazole-5-carbonyl)-propyl]-butyramide; 2-(2-Moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, (S)-l-(3-phenyl-l,2,4-oxadiazole-5-carbonyl)-propyl}-amide; N-[(lS)-l-(Benzooxazol-2-yl-hydroxy-methyl)-3-phenyl-propyl]-2- cyclopropylmethylsulfonylmethyl-4-moφholin-4-yl-4-oxo-butyr-U_ιide; (R)-2-((S)-l-Hydroxy-2-moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, 1 -(benzoxazole-2-carbonyl)-propyl] -amide; (R)-5-(2-Difluoromethoxy-phenyl)-2-((S)-l-hydroxy-2-moφholin-4-yl-2-oxo-ethyl)- pentanoic acid, l-(benzoxazole-2-carbonyl)-propyl] -amide; 4-Moφholin-4-yl-Ν-[l-(oxazole-2-carbonyl)-cyclopropyl]-4-oxo-2-benzylsulfonyl methyl -butyramide; N-[(S)-l-((E)-2-benzenesulfonyl-vinyl)-pentyl]-3-benzylsulfonyI-2-benzylsulfonylmethyl- propionamide N-(3-benzenesulfonyl-l-phenethyl-allyl)-3-benzylsulfonyl-2-benzylsulfonylmethyl- propionamide; N-(3-benzenesulfonylamino-2-oxo-propyl)-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide; (S)-2,2-difluoro-4-(4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butanoylamino)-3- oxo-hexanoic acid dimethylamide; N-[(S)-l-(l-Benzylcarbamoyl-methanoyl)-propyl]-3-benzylsulfonyl-2- beπzylsulfonylmethyl-propionamide; N-[(S)-l-(l-Benzylcarbamoyl-methanoyl)-propyl]-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide; 3-Hydroxy-4-(4-moφholin-4-yl-4-oxo-2-be__-ylsulfonylmemyl-but^lamino)-azepane-l- carboxylic acid tert-butyl ester; 4-(2-Cyclopropylmemylsulfonylmethyl-4-moφholin-4-yl-4-oxo-buι^lamino)-3-hydroxy- azepane-1 -carboxylic acid tert-butyl ester; 3-Hydroxy-4-[2-(2-methyl-propane-l-sulfonylmethyl)-4-moφholin-4-yl-4-oxo- butyrylamino]-azepane-l -carboxylic acid tert-butyl ester; 4-(4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyrylamino)-3-oxo-azepane-l- carboxylic acid tert-butyl ester; 4-(2-Cyclopropylmethylsulfonylmethyl-4-moφholin-4-yl-4-oxo-butyrylamino)-3-oxo- azepane-1 -carboxylic acid tert-butyl ester; 4-[2-(2-Methyl-propane-l-sulfonylmemyl)-4-moφholin-4-yl-4-oxo-bul^τylarnino]-3-oxo- azepane-1 -carboxylic acid tert-butyl ester; N-(l-Benzenesulfonyl-3-oxo-azepan-4-yl)-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide; N-(l-BenzenesuIfonyl-3-oxo-azepan-4-yl)-2-(2-methyl-propane-l-sulfonylmethyl)-4- moφholin-4-yl-4-oxo-butyramide; 3-(4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyrylamino)-4-oxo-pyrrolidine-l- carboxylic acid tert-butyl ester; 4-(4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyrylamino)-3-oxo-azepane-l- carboxylic acid benzyl ester; acetic acid (2S,3S)-3-(4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butanoylamino)-4- oxo-azetidin-2-yl ester;and their corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof. Preferred compounds of the invention are:- N- [(S)- 1 -(1 -benzooxazol-2-yl-memanoyl)-butyl]-3^ propionamide (compound denoted as A64-B4-C11-D6), (Compound 1); N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-butyl]-3-(2-trifluoromethyl-benzylsulfonyl)-2- (2-trifluoromethyl-benzylsulfonylmethyl)-propionamide, (compound denoted as A69-B32-C11-D6), (Compound 2); N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-pentyl]-4-(2-methoxy-benz;enesulfonyl)-2-[2-(2- methoxy-benzenesulfonyl)-ethyl]-butyramide, (compound denoted as A64-B85-C11-D6), (Compound 3); 4-benzenesulfonyl-2-(2-benzenesulfonyl-ethyl)-N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)- butyl] -butyramide, (compound denoted as A4-B6-C11-D6), (Compound 4); (R)-N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-butyl]-2-cyclohexylmethyl-3- benzylsulfonyl-propionamide, (Compound 5) ; N- [(S)- 1 -( 1 -benzooxazol-2-yl-me thanoyl)-butyl] -3-isobutylsulf anyl-2- isobutylsulfanylmethyl-propionamide, (compound denoted as A68-B79-C11-D6), (Compound 8); N-[(S)-l-(l-benzooxazol-2-yl-memanoyl)-butyl]-3-benzylsulfanyl-2-benzylsulfanylmethyl- propionamide, (compound denoted as A64-B85-C11-D6), (Compound 9); N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-butyl]-4-phenylsulfanyl-2-(2-phenylsulfanyl- ethyl)-butyramide, (compound denoted as A70-B80-C6-D6), (Compound 10); N-cyanomethyl-2-[2-( 1 , 1 -difluoro-methoxy)-benzylsulfonylmethyl] -4-moφholin-4-yl-4- oxo-butyramide, (compound denoted as A2-B39-C1-D1), (Compound 25); N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-propyl]-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide, (compound denoted as A2-B4-C6-D6), (Compound 29); N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-pentyl]-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide, (compound denoted as A2-B4-C9-D6), (Compound 30); N-[(S)-l-(l-benzylcarbamoyl-methanoyl)-propyl]-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmemyl-butyramide, (compound denoted as A2-B4-C6-D8), (Compound 32); N-[(S)-l-((Ε)-2-benzenesulfonyI-vinyl)-pen-yl]-3-benzylsulfonyl-2-benj zylsuIfonylmethyl- propionamide, (compound denoted as A13-B4-C9-D7), (Compound 38); Ν-(3-Benzenesulfonyl-l-phenethyl-allyl)-3-benzylsulfonyl-2-benzylsulfonylmethyl- propionamide, (compound denoted as A13-B4-C10-D7), (Compound 39) ; N-cyanomethyl-3-(3-cyano-benzylsulfonyl)-2-benzylsulfonyl-methyl-propionamide, (compound denoted as A89-B4-C1-D1), (Compound 40); 4-moφholin-4-yl-4-oxo-2-ber_zylsulfonylmethyl-N- { (S)- 1 -[ 1 -(3-phenyl-[ 1 ,2,4]oxadiazol- 5-yl)-methanoyl]-propyl}-butyramide, (compound denoted as A2-B4-C6-D10), (Compound 41); Ν-cyanomethyl-2- [2-1,1 -difluoro-methoxy)-benzylsulf onylmethyl] -3-benzylsulfonyl- propionamide, (compound denoted as A13-B39-C1-D1), (Compound 48); N-cyanomethyl-3-[2-(lJ-difluoro-methoxy)-benzylsulfonyl]-2-[2-(lJ-difluoro-methoxy)- benzylsulfonylmethyl]-propionamide, (compound denoted as A5-B39-C1-D1), (Compound 51); N-[(S)-l-(l-benzylcarbamoyl-methanoyl)-propyl]-3-benzylsulfonyl-2- benzylsulfonylme yl-propionamide, (compound denoted as A13-B4-C6-D8), (Compound 53); N- [(S)- 1 -( 1 -benzooxazol-2-yl-methanoyl)-butyl] -2- [2-( 1 , 1 -difluoro-methoxy)- benzylsulfonylmethyl]-3-benzylsulfonyl-propionamide, (compound denoted as A13-B39- C11-D6), (Compound 54); acetic acid (2S,3S)-3-(4-moφholin-4-yl-4-oxo-2-benzylsulfonylmemyl-butanoylamino)-4- oxo-azetidin-2-yl ester, (compound denoted as A2-B4-E4), (Compound 58); N-cyanomethyl-3-(2-methyl-thiazol-4-ylmethylsulfonyl)-2-benzyl-sulfonylmethyl- propionarnide, (compound denoted as A114-B4-C1-D1), (Compound 59); and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual stereoisomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. Especially preferred compounds of the invention are:- N-[(S)-l-(l-benzooxazol-2-yl-memanoyl)-butyl]-3-beι__ylsulfonyl-2-benzylsulfonylmethyl- propionamide (compound denoted as A64-B4-C11-D6), (Compound 1); 4-benzenesulfonyl-2-(2-benzenesulfonyl-ethyl)-N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)- butyl]-butyramide, (compound denoted as A4-B6-C11-D6), (Compound 4); N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-propyl]-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide (compound denoted as A2-B4-C6-D6), (Compound 29); N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-pentyl]-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide, (compound denoted as A2-B4-C9-D6), (Compound 30); N-[(S)-l-(l-benzylcarbamoyl-methanoyl)-propyl]-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide, (compound denoted as A2-B4-C6-D8), (Compound 32); N-[(S)-l-((E)-2-ber_-enesulfonyl-vinyl)-pentyl]-3-benzylsulfonyl-2-benzylsulfonylmethyl- propionamide, (compound denoted as A13-B4-C9-D7), (Compound 38); Ν-(3-Benzenesulfonyl-l-phenethyl-allyl)-3-benzylsulfonyl-2-benzylsulfonylmethyl- propionamide, (compound denoted as A13-B4-C10-D7), (Compound 39) ; 4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N- { (S)- 1 - [ 1 -(3-phenyl- [ 1 ,2,4] oxadiazol- 5-yl)-mefhanoyl]-propyl}-butyramide, (compound denoted as A2-B4-C6-D10), (Compound 41); N-[(S)-l-(l-benzylcarbamoyl-methanoyl)-propyl]-3-benzylsulfonyl-2- benzylsulfonylmethyl-propionamide, (compound denoted as A13-B4-C6-D8), (Compound 53); N- [(S)- 1 -(1 -benzooxazol-2-yl-methanoyl)-butyl] -2- [2-( 1 , 1 -difluoro-methoxy)- benzylsulfonylmethyl]-3-benzylsulfonyl-propionamide, (compound denoted as A13-B39- C11-D6), (Compound 54); and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual stereoisomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. Pharmacology and Utility: The compounds of the invention are selective inhibitors of cathepsin S and, as such, are useful for treating diseases in which cathepsin S activity contributes to the pathology and/ or symptomatology of the disease. For example, the compounds of the invention are useful in treating autoimmune disorders, including, but not limited to, juvenile onset diabetes, multiple sclerosis, pemphigus vulgaris, Graves' disease, myasthenia gravis, systemic lupus erythemotasus, rheumatoid arthritis and Hashimoto's thyroiditis, allergic disorders, including, but not limited to, asthma, and allogeneic immune responses, including, but not limited to, organ transplants or tissue grafts. Cathepsin S also is implicated in disorders involving excessive elastolysis, such as chronic obstructive pulmonary disease (e.g., emphysema), bronchiolitis, excessive airway elastolysis in asthma and bronchitis, pneumonities and cardiovascular disease such as plaque rupture and atheroma. Cathepsin S is implicated in fibril formation and, therefore, inhibitors of cathepsins S are of use in treatment of systemic amyloidosis. The cysteine protease inhibitory activities of the compounds of the invention can be determined by methods known to those of ordinary skill in the art. Suitable in vitro assays for measuring protease activity and the inhibition thereof by test compounds are known. Typically, the assay measures protease-induced hydrolysis of a peptide-based substrate. Details of assays for measuring protease inhibitory activity are set forth in Examples 69, 70, 71 and 72, infra. Administration and Pharmaceutical Compositions: In general, compounds of Formula I will be administered in therapeutically effective amounts via any of the usual and acceptable modes known in the art, either singly or in combination with one or more therapeutic agents. A therapeutically effective amount may vary widely depending on the severity of the disease, the age and relative health of the subject, the potency of the compound used and other factors. For example, therapeutically effective amounts of a compound of Formula I may range from about 1 micrograms per kilogram body weight (μg/kg) per day to about 1 milligram per kilogram body weight (mg/kg) per day, typically from about 10 μg/kg/day to about 0.1 mg/kg/day. Therefore, a therapeutically effective amount for a 80 kg human patient may range from about 100 μg/day to about 100 mg/day, typically from about 1 μg/day to about 10 mg/day. In general, one of ordinary skill in the art, acting in reliance upon personal knowledge and the disclosure of this Application, will be able to ascertain a therapeutically effective amount of a compound of Formula I for treating a given disease. The compounds of Formula I can be administered as pharmaceutical compositions by one of the following routes: oral, systemic (e.g., transdermal, intranasal or by suppository) or parenteral (e.g., intramuscular, intravenous or subcutaneous). Compositions can take the form of tablets, pills, capsules, semisolids, powders, sustained release formulations, solutions, suspensions, elixirs, aerosols, or any other appropriate composition and are comprised of, in general, a compound of Formula I in combination with at least one pharmaceutically acceptable excipient. Acceptable excipients are non-toxic, aid administration, and do not adversely affect the therapeutic benefit of the active ingredient. Such excipient may be any solid, liquid, semisolid or, in the case of an aerosol composition, gaseous excipient that is generally available to one of skill in the art. Solid pharmaceutical excipients include starch, cellulose, talc, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, magnesium stearate, sodium stearate, glycerol monostearate, sodium chloride, dried skim milk, and the like. Liquid and semisolid excipients may be selected from water, ethanol, glycerol, propylene glycol and various oils, including those of petroleum, animal, vegetable or synthetic origin (e.g., peanut oil, soybean oil, mineral oil, sesame oil, and the like). Preferred liquid carriers, particularly for injectable solutions, include water, saline, aqueous dextrose and glycols. The amount of a compound of Formula I in the composition may vary widely depending upon the type of formulation, size of a unit dosage, kind of excipients and other factors known to those of skill in the art of pharmaceutical sciences. In general, a composition of a compound of Formula I for treating a given disease will comprise from 0.01%w to 10%w, preferably 0.3%w to l%w, of active ingredient with the remainder being the excipient or excipients. Preferably the pharmaceutical composition is administered in a single unit dosage form for continuous treatment or in a single unit dosage form ad libitum when relief of symptoms is specifically required. Representative pharmaceutical formulations containing a compound of Formula I are described in Example 73. Chemistry: Processes for Making Compounds of Formula I: Compounds of the invention may be prepared by the application or adaptation of known methods, by which is meant methods used heretofore or described in the literature, for example those described by R.C. Larock in Comprehensive Organic Transformations, VCH publishers, 1989. In the reactions described hereinafter it may be necessary to protect reactive functional groups, for example hydroxy, amino, imino, thio or carboxy groups, where these are desired in the final product, to avoid their unwanted participation in the reactions. Conventional protecting groups may be used in accordance with standard practice, for examples see T.W. Greene and P. G. M. Wuts in "Protective Groups in Organic Chemistry" John Wiley and Sons, 1991. Compounds of Formula I, where X 1 is -NHC(R 1 )(R 2 )X 2 , can be prepared by proceeding as in the following Reaction Scheme 1: Reaction Scheme 1 NHaCR^X 2 in which each X", R 1 , R , R J and R are as defined for Formula I in the Summary of the Invention. Compounds of Formula I can be prepared by condensing an acid of Formula 2 with an amino compound of formula NH 2 CR : R 2 X 2 . The condensation reaction can be effected with an appropriate coupling agent (e.g., benzotriazol-1-yloxytrispyrrolidinophosphonium hexafluorophosphate (PyBOP ® ), l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), O-benzotriazol-l-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU), 1,3-dicyclohexylcarbodiimide (DCC), or the like) and optionally an appropriate catalyst (e.g., 1 -hydroxybenzotriazole (HOBt), 1-hydroxy- 7-azabenzotriazole (HOAt), O-(7-azabenzotrizol-l-yl)-l, 1,3,3, . tetra- methyluroniumhexafluorophosphate (HATU), or the like) and non-nucleophilic base (e.g., triethylamine, N-methylmoφholine, and the like, or any suitable combination thereof) at ambient temperature and requires 5 to 10 hours to complete. An oxidation step, if required, can be carried out with an oxidizing agent (e.g., Oxone ® , metachloroperbenzoic acid or the like) in a suitable solvent (e.g., methanol, water, or the like, or any suitable combination thereof) at ambient temperature and requires 16 to 24 hours to complete. Detailed descriptions for the synthesis of a compound of Formula I by the processes in Reaction Scheme 1 are set forth in the Examples 1 to 6, infra. Compounds of Formula I, where X 1 is -ΝHX 3 , can be prepared by proceeding as in the following Reaction Scheme 2: Reaction Scheme 2 NH 2 X j in which each X 3 , R 3 and R 4 are as defined for Formula I in the Summary of the vention. Compounds of Formula I can be prepared by condensing an acid of Formula 2 with an amino compound of formula NH 2 X 3 . The condensation reaction can be effected with an appropriate coupling agent (e.g., benzotriazol-1-yloxytrispyrrolidinophosphonium hexafluorophosphate (PyBOP ® ), l-(3-dimemylaminopropyl)-3-ethylcarbodiirαide hydrochloride (EDCI), O-benzotriazol-l-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU), 1,3-dicyclohexylcarbodiimide (DCC), or the like) and optionally an appropriate catalyst (e.g., 1 -hydroxybenzotriazole (HOBt), 1-hydroxy- 7-azabenzotriazole (HOAt), 0-(7-azabenzotrizol-l-yl)-l,l,3,3, terra- methyluroniumhexafluorophosphate (HATU), or the like) and non-nucleophilic base (e.g., triethylamine, N-methylmoφholine, and the like, or any suitable combination thereof) at ambient temperature and requires 5 to 10 hours to complete. An oxidation step, if required, can be carried out with an oxidizing agent (e.g., Oxone ® , metachloroperbenzoic acid or the like) in a suitable solvent (e.g., methanol, water, or the like, or any suitable combination thereof) at ambient temperature and requires 16 to 24 hours to complete. Compounds of Formula 2 can be prepared by reacting a compound of Formula 3 with a compound of Formula R 3 L: 3 in which L is a leaving group and R 3 and R 4 are as defined in the Summary of the Invention. The reaction involves coupling (or alkylation) followed by alkaline hydrolysis at a temperature during which the dicarboxylic acid formed undergoes mono- decarboxylation. The coupling reaction can be carried out in the presence of a suitable base (e.g. triethylamine) in a suitable solvent (e.g. ethanol). The decarbalkoxylation can be effected under strongly basic conditions (e.g. in the presence of IN aqueous sodium hydroxide) in a suitable solvent (e.g. ethanol). Detailed descriptions for the synthesis of compounds of Formula 2 by the process described above are set forth in the References, infra. Compounds of Formula 2, in which R 3 and R 4 are benzylsulfonylmethyl, can be prepared by reacting a compound of Formula 4: in which R 30 is a halo group, with benzyl mercaptan under strongly basic conditions to produce a compound of Formula 5: followed by reaction with benzyl mercaptan in the presence of a suitable coupling reagent (e.g. DMAP) and in a suitable solvent (e.g. DMF). A detailed description of the synthesis of a compound of Formula 2 by a similar process as that described above is set forth in the References, infra. Compounds of Formula 2, in which R 4 is biaryl, can be prepared by coupling a compound of Formula 6: in which R 30 is a halo group and R 3 is as defined in the Summary of the Invention, with a compound of ArL, in which Ar is an aryl group and L is a leaving group, to produce a compound of Formula 2 in which R 4 is biaryl. The coupling reaction takes place in the presence of a suitable catalyst (e.g. tetrakis-triphenylphosphine palladium). A detailed description of the synthesis of a compound of Formula 2 by the process described above is set forth in the References, infra. Additional Processes for Preparing Compounds of Formula I: A compound of Formula I can be prepared as a pharmaceutically acceptable acid addition salt by reacting the free base form of the compound with a pharmaceutically acceptable inorganic or organic acid. Alternatively, a pharmaceutically acceptable base addition salt of a compound of Formula I can be prepared by reacting the free acid form of the compound with a pharmaceutically acceptable inorganic or organic base. Inorganic and organic acids and bases suitable for the preparation of the pharmaceutically acceptable salts of compounds of Formula I are set forth in the definitions section of this Application. Alternatively, the salt forms of the compounds of Formula I can be prepared using salts of the starting materials or intermediates. The free acid or free base forms of the compounds of Formula I can be prepared from the corresponding base addition salt or acid addition salt form. For example, a compound of Formula I in an acid addition salt form can be converted to the corresponding free base by treating with a suitable base (e.g., ammonium hydroxide solution, sodium hydroxide, and the like). A compound of Formula I in a base addition salt form can be converted to the corresponding free acid by treating with a suitable acid (e.g., hydrochloric acid, etc). The N-oxides of compounds of Formula I can be prepared by methods known to those of ordinary skill in the art. For example, N-oxides can be prepared by treating an unoxidized form of the compound of Formula I with an oxidizing agent (e.g., trifluoroperacetic acid, permaleic acid, perbenzoic acid, peracetic acid, rnet -chloroperoxybenzoic acid, or the like) in a suitable inert organic solvent (e.g., a halogenated hydrocarbon such as dichloromethyl) at approximately 0°C. Alternatively, the N-oxides of the compounds of Formula I can be prepared from the N-oxide of an appropriate starting material. Compounds of Formula I in unoxidized form can be prepared from N-oxides of compounds of Formula I by treating with a reducing agent (e.g., sulfur, sulfur dioxide, triphenyl phosphine, lithium borohydride, sodium borohydride, phosphorus trichloride, tribromide, or the like) in an suitable inert organic solvent (e.g., acetonitrile, ethanol, aqueous dioxane, or the like) at 0 to 80°C. Prodrug derivatives of the compounds of Formula I can be prepared by methods known to those of ordinary skill in the art (e.g., for further details see Saulnier etal.(1994), Bioorganic and Medicinal Chemistry Letters, Vol.4, p. 1985). For example, appropriate prodrugs can be prepared by reacting a non-derivatized compound of Formula I with a suitable carbamylating agent (e.g., 1,1-acyloxyalkylcarbonochloridate, rα-nitrophenyl carbonate, or the like). Protected derivatives of the compounds of Formula I can be made by means known to those of ordinary skill in the art. A detailed description of the techniques applicable to the creation of protecting groups and their removal can be found in T.W. Greene, Protecting Groups in Organic Synthesis, 3 rd edition, John Wiley & Sons, Inc. 1999. Compounds of the present invention may be conveniently prepared, or formed during the process of the mvention, as solvates (e.g. hydrates). Hydrates of compounds of the present invention may be conveniently prepared by recrystallisation from an aqueous/organic solvent mixture, using organic solvents such as dioxin, tetrahydrofuran or methanol. Compounds of Formula I can be prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds, separating the diastereomers and recovering the optically pure enantiomer. While resolution of enantiomers can be carried out using covalent diasteromeric derivatives of compounds of Formula I, dissociable complexes are preferred (e.g., crystalline diastereoisomeric salts). Diastereomers have distinct physical properties (e.g., melting points, boiling points, solubilities, reactivity, etc.) and can be readily separated by taking advantage of these dissimilarities. The diastereomers can be separated by chromatography or, preferably, by separation/resolution techniques based upon differences in solubility. The optically pure enantiomer is then recovered, along with the resolving agent, by any practical means that would not result in racemization. A more detailed description of the techniques applicable to the resolution of stereoisomers of compounds from their racemic mixture can be found in Jean Jacques Andre Collet, Samuel H. Wilen, Enantiomers, Racemates and Resolutions, John Wiley & Sons, Inc. (1981). In summary, the compounds of Formula I are made by a process which comprises: (A) reacting a compound of Formula 2: 2 with a compound of the formula MELCR^X 2 , in which X 2 , R 1 , R 2 , R 3 and R 4 are as defined in the Summary of the Invention for Formula I; or (B) reacting a compound of Formula 2 with a compound of the formula NH 2 X 3 , in which X 3 , R 3 and R 4 are as defined in the Summary of the Invention for Formula I; or (C) optionally converting a compound of Formula I into a pharmaceutically acceptable salt; (D) optionally converting a salt form of a compound of Formula I to non-salt form; (E) optionally converting an unoxidized form of a compound of Formula I into a pharmaceutically acceptable N-oxide; (F) optionally converting an N-oxide form of a compound of Formula I its unoxidized form; (G) optionally resolving an individual isomer of a compound of Formula I from a mixture of isomers; (H) optionally converting a non-derivatized compound of Formula I into a pharmaceutically prodrug derivative; and (I) optionally converting a prodrug derivative of a compound of Formula I to its non-derivatized form. Examples: The present invention is further exemplified, but not limited by, the following examples that illustrate the preparation of compounds of Formula I (Examples) and intermediates (References) according to the invention. REFERENCE 1 3-Benzylsulfanyl-2-benzylsulfanylmethyl-propionic acid A solution of diethyl bis(hydroxymethyl)malonate (46.95g, 0.21 moles) (prepared by the method of P. Block, Jr., Organic Synthesis, Collective Volume V, 381 (1973)) in methylene chloride (500mL) was treated with triethylamine (63mL) and cooled to -30°C. A mixture of methylsulfonyl chloride (35 mL) in methylene chloride (40 mL) was added to the reaction mixture dropwise over 20 minutes and the reaction mixture was allowed to stir at room temperature for 18 hours. The reaction mixture was then poured into ice water and the product was extracted with methylene chloride. The organic extracts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure and the residue was recrystallized from t-butylmethyl ether and hexane to give 2,2-bis-methylsulfonyloxymethyl-malonic acid diethyl ester (55.04 g). Sodium (0.268 g, 11.6 mmol) was dissolved in ethanol (25 mL) and the resulting solution was treated with benzyl mercaptan (1.87 mL, 15.9 mmol). The reaction mixture was cooled on ice and the 2,2-bis-methylsulfonyloxymethyl-malonic acid diethyl ester (2.00g, 5.31 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours and then heated at 55°C for 1.5 hours. The resulting solution was cooled to room temperature and poured into ice water. The product was extracted with ethyl acetate. The extracts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure and the residue was chromatographed on silica gel eluting with ethyl acetate/hexane to give 3-benzylsulfanyl-2-benzylsulfanylmethyl-propionic acid ethyl ester (1.589 g, 83% yield). 3-Benzylsulfanyl-2-benzylsulfanylmethyl-propionic acid ethyl ester (1.589 g, 4.41 mmol) in a mixture of potassium hydroxide (IN, 7 mL), water (3 mL), dioxane (30 mL) and ethanol (10 mL) was stirred at room temperature for 18 hours. The solvents were removed form the reaction mixture by rotary evaporation at reduced pressure and the residue was dissolved in water and washed with ether. The aqueous layer was cooled on ice, acidified to pH 2 and the product extracted with ethyl acetate. The extracts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure to give 3- benzylsulfanyl-2-benzylsulfanylmethyl-propionic acid (1.293g, 88%). REFERENCE 2 2-Benzylsulfanylmethyl-3-r2-( " l,l-difluoro-methoxy)-benzylsulfanyl]-propionic acid 2-Bromomethylacrylic acid (3.00 g, 18.1 mmol) was dissolved in methanol (lOOmL), cooled on an ice bath and treated with benzyl mercaptan. Aqueous sodium hydroxide (IN, 39.8 mL) was added dropwise and the reaction mixture was allowed to adjust to room temperature with stirring for 23 hours. Methanol was removed by rotary evaporation at reduced pressure and water (100 mL) was added to the residue, which was then washed with ether. The aqueous layer was cooled on ice and acidified to pH 2.5. The precipitated solid was isolated by filtration and dried to give 2-benzylsulfanylmethyl- acrylic acid (3.346 g, 89 %). A solution of 2-difluoromethoxybenzyl mercaptan (0.534 g, 2.81 mmol), 2- benzylsulfanylmethyl-acrylic acid (0.585 g, 2.81 mmol) and4-dimethylaminopyridine (36 mg, 0.3 mmol) in DMF (1.5 ml) was stirred at room temperature for 20 hours. An additional amount of 2-difluoromethoxybenzyl mercaptan (0.201 g) was added to the reaction mixture and stirring was continued for another 24 hours. The reaction mixture was poured into dilute, cold, aqueous HCl and the product extracted with ethyl acetate. The extracts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure and the residue was chromatographed on silica gel eluting with ethyl acetate/hexane to give 2-Benzylsulfanylmethyl-3-[2-(l,l-difluoro-methoxy)-benzylsulfanyl]-propio_ c acid (0.706 g)- REFERENCE 3 2-Benzylsulfanylmethyl-3-cyclohexyl-propiomc acid A solution of diethyl-2-cyclohexylmethyl malonate (2.56 g), 37% aqueous formaldehyde (0.80 mL), potassium bicarbonate (0.08g) and ethanol (2.5 mL) was stirred at room temperature for 20 hours. Saturated aqueous ammonium sulfate (10 mL) was added to the reaction and the product extracted with ethyl acetate. The extracts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure and the residue was chromatographed on silica gel eluting with ethyl acetate/hexane to give 2- cyclohexylmethyl-2-hydroxymethyl-malonic acid diethyl ester (1.31g). A solution of 2-cyclohexylmethyl-2-hydroxymethyl-malonic acid diethyl ester (1.31 g, 4.13 mmol) in methylene chloride (20 mL) and triethyl amine (1.16 mL, 8.00 mmol) was cooled to -40°C. A solution of methylsulfonyl chloride (0.402 mL, 5.2 mmol) in methylene chloride (4 mL) was added to the reaction mixture over 5 minutes. The reaction mixture was warmed to -10°C over 1 hour and then poured into cold dilute aqueous HC The product was extracted with ethyl acetate, the extracts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure to give 2-cyclohexylmethyl-2- methylsulfonyloxymethyl-malonic acid diethyl ester (1.505 g). Sodium (0.097 g, 4.2 mmol) was dissolved in ethanol (10 mL) and the resulting solution was cooled to 0°C and treated with a mixture comprising benzyl mercaptan (0.493 mL, 4.2 mmol) and 2-cyclohexylmethyl-2-methylsulfonyloxymethyl-malonic acid diethyl ester (1.466 g, 4.02 mmol). The reaction was stirred at room temperature for 17 hours, 53°C for 20 hours and 73°C for 24 hours. The ethanol was removed by rotary evaporation, the reaction mixture was poured into water and the product was extracted with ethyl acetate. The extracts were washed with saturated aqueous sodium chloride and then dried . over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure and the residue was chromatographed on silica gel eluting with ethyl acetate/hexane to give 2-benzylsulfanylmethyl-3-cyclohexyl-propionic acid ethyl ester (0.237 g). A mixture of 2-benzylsulfanylmethyl-3-cyclohexyl-propionic acid ethyl ester (0.230g), dioxane (10 mL), sodium hydroxide (IN, 3 mL), water (2 mL) and ethanol (4 mL) was stirred for 20 hours at room temperature. The solvents were evaporated and the residue dissolved in water (50 mL). The aqueous solution was washed twice with ether and then acidified to pH2. The product was extracted from the aqueous solution with ethyl acetate and the extracts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure to give acid 2-benzylsulfanylmethyl-3-cyclohexyl-propionic acid (0.210 g). REFERENCE 4 4-Benzenesulfonyl-2-(2-benzenesulfonyl-ethyl)-butyric acid A mixture of 2-iodoethylphenyl sulfide (19.81g, 75mmol), diethyl malonate (4.80g, 30mmol), potassium carbonate (10.35g, 75mmol) and DMF (40mL) was heated at 52°C for 18 hours. More potassium carbonate (lOg) was added and the reaction was continued at 52°C for another 8 hours. The reaction mixture was cooled, diluted with ice water and the product extracted with ethyl acetate. The extracts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure and the residue was chromatographed on silica gel eluting with ethyl acetate/hexane to give 2,2-bis-(2-phenylsulfanyl-ethyl)-malonic acid diethyl ester (5.648g). A solution of 2,2-bis-(2-phenylsulfanyl-ethyl)-malonic acid diethyl ester (5.614g) in ethanol (lOOmL) was treated with lithium hydroxide (2.84g) in water (lOmL). The reaction mixture was heated at 49°C for 17 hours followed by 85 °C for 2 hours. The solvents were evaporated at reduced pressure to give a residue that was treated with water (lOOmL) and washed with ether. The aqueous layer was cooled on ice, acidified and the product extracted with ethyl acetate. The extracts were dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure to give acid 2,2-bis-(2- phenylsulfanyl-ethyl)-malonic acid (5.628 g). 2,2-Bis-(2-phenylsulfanyl-ethyl)-malonic acid (5.628 g) was heated at 150°C for 30 minutes. The reaction mixture was cooled to room temperature, dissolved in ethyl acetate and washed with aqueous sodium bicarbonate. The ethyl acetate solution was washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure and the residue was chromatographed on silica gel eluting with ethyl acetate/hexane to give 4-phenylsulfanyl-2- (2-phenylsulfanyl-ethyl)-butyric acid (1.831 g). A solution of 4-phenylsulfanyl-2-(2-phenylsulfanyl-ethyl)-butyric acid (0.332g) in methanol (lOmL) was treated with a solution of Oxone ® (1.87g in lOmL of water). After stirring 18 hours at room temperature the reaction mixture was diluted with water (30mL) and evaporated under reduced pressure to remove the methanol. The product was extracted with ethyl acetate. The extracts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation and the resulting oil was crystallized from t-butylmethyl ether to give 4-benzenesulfonyl-2-(2- benzenesulfonyl-ethyl)-butyric acid (0.315g). REFERENCE 5 4-Moφholin-4-yl-4-oxo-2-(2-trifluoromemyl-benzylsulfonylmethyl)-butyric acid A solution of 3-methylene-dihydro-furan-2,5-dione (5.9g, 52.7mmol) in CH 2 C1 2 (200mL) was cooled to 0°C before adding moφholine (4.6mL, 52.7mmol) slowly over 5 minutes. The ice bath was removed and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under vacuum to 2-Methylene-4-moφholin-4-yl-4-oxα- butyric acid. A mixture of 2-methylene-4-moφholin-4-yl-4-oxo-butyric acid (2g, 10.03mmol),in DMF (5mL), 2-trifluoromethylbenzyl mercaptan (1.93g, 10.03mmol) and DMAP (122mg, l.Ommol) was stirred at ambient temperature for 16 hours. Methanol (200mL) and a saturated aqueous solution of Oxone ® (20g, 32.5mmol) were added with continued stirring for 2 hours. Methanol was removed under vacuum and the aqueous residue was diluted with 200mL of water. The crystallized product was filtered, washed with water, and dried under vacuum to yield 4-morpholin-4-yl-4-oxo-2-(2-trifluoromethyl- benzylsulfonylmethyD-butyric acid (0.95g) as a white solid. Compounds of Formula I in which R 3 is -CH 2 SR 14 (R 14 is as described in the summary of the invention) can be synthesized by the following reaction protocol: Compound 1 was prepared as S or R enantiomers using the method described by Crawforth et al. J. Chem. Soc, Perkin Trans. 1, 1721-1725,1998. Compound 2 was prepared by dissolving compound 1 in methylene chloride with triphenylphosphine (1.1 equivalents) followed by the slow addition of N- bromosuccinamide (1.05 equivalents) over a 5 minute period and the reaction was allowed to stir for 3 -8 hours at room temperature. The mi ture was then extracted with water and brine, then dried over sodium sulfate. After concentrating the residue was dissolved in ether and a small amount of heptane was added to remove unwanted solids. After filtering and concentration the resulting bromide was used without further purification. This intermediate was dissolved in THF then potassium thioacetate (1.1 equivalents) was added in one portion and the reaction was stirred for 3 to 24 hours at room temperature. The solvent was removed and the residue taken up in ethanol. Sodium hydroxide was added (2.2 equivalents) and the reaction was stirred for 10 to 60 minutes at room temperature. 1 equivalent of a halo-substituted compound (eg. benzyl bromide, isobutyl bromide, cyclopropylmethyl bromide; see other elements from table 2, supra) was added with stirring for 6 to 24 hours at room temperature. The ethanol was removed under vacuum and the mixture was diluted with water and made acidic with 4 Ν HCl (pH=l to 2). The aqueous layer was extracted with ethyl acetate 3 times and the organic layer was dried over sodium sulfate and concentrated. The product was purified on silica gel using a mixture of ethyl acetate and heptane (gradient 1:4 to 4:1) to give compound 2. Compound 3 was made by stirring a solution of compound 2 in THF with moφholine (2 equivalents), which was heated, to reflux for 1 to 24 hours. Concentration of the mixture and redissolving in methylene chloride and exttaction with diluted HCl removed the excess moφholine. The organic layer was washed with saturated sodium bicarbonate, dried over sodium sulfate and concentrated to dryness. The product was purified on silica gel using a mixture of ethyl acetate and heptane (gradient 1 :4 to 4: 1) to give compound 3. Compound 4 was prepared from compound 3 by dissolving in a 1:1 mixture of methanol/water and adding oxone® (approximately 1 equivalent) over a period of 1 to 3 hours until a positive starch-iodine test was maintained. The solvent was removed under vacuum and the residue dissolved in a 1:1:1 mixture of water/acetonitrile/carbon tetrachloride. This was followed by the addition of sodium periodate and ruthenium (HI) chloride which was vigorously stirred for 6 to 24 hours at a temperature below 40°C. The reaction was filtered through celite and concentrated to remove acetontrile and carbon tetrachloride. The aqueous layer was extracted with ethyl acetate 3 times and the organic layer dried over sodium sulfate and concentrated. The product was purified on silica gel using a mixture of ethyl acetate and heptane (1 :4 to 4: 1) to ethyl acetate and methanol (19:1 to 4: 1) to give compound 4, which was obtained as R or S enantiomers. REFERENCE 6 (S)-4-Amino-2,2-difluoro-3-hydroxy-hexanoic acid dimethylamide Activated zinc dust (2.16g, 33mmol) was suspended in dry THF (2mL). A mixture of ethyl bromodifluoro acetate (6.5g, 32mmol) and (lS)-(l-formyl-propyl) carbainic acid tert-butyl ester (2g, 10.7mmol), in THF (lOmL), was added over 20 minutes while the mixture was sonicated. After complete addition, sonication was continued for a further 30 minutes. The mixture was then diluted with ethyl acetate (200mL) and washed with IN aqueous KHSO 4 , brine, dried with magnesium sulfate and evaporated. The crude product was dissolved in ethanol (15mL) and a solution of dimethylamine (40% in water; 2mL) was added. After stirring for 16 hours at ambient temperature, the solvents were evaporated and the product was purified by flash chromatography on silica gel (hexane/ethyl acetate ratio of 3: 1) to yield 200mg of colorless oil. The amide was dissolved in a mixture of TFA/dichloromethyl (1:1; 6mL), stirred for 1 hour and evaporated to dryness. The product, (4S)- 4-amino-2,2-difluoro-3-hydroxy- hexanoic acid dimethylamide, was obtained as the TFA salt and used without further purification. REFERENCE 7 (S)-3-Amino-2-hvdroxy-pentanoic acid benzylamide (lS)-(2-Cyano-l-ethyl-2-hydroxyethyl)carbamic acid tert-butyl ester (lOg, 46.7mmol) was dissolved in 1,4-dioxane (lOOmL). Anisole (5mL) was added and then concentrated HCl (lOOmL). The mixture was heated under reflux for 24 hours. The mixture was evaporated to dryness under vacuum and re-dissolved in lOOmL water. The solution was washed with ether and then neutralized with saturated aqueous NaHCO 3 . Di- tert-butyl dicarbonate (lOg, 46mmol) was added with 1,4-dioxane (200mL), and the mixture was stirred at ambient temperature for 24 hours. The dioxane was removed under vacuum and the remaining aqueous solution was washed with ether. The solution was acidified with IN HCl and extracted with ethyl acetate. The combined organic layers were washed with brine, dried with magnesium sulfate and evaporated to yield 3-tert- Butoxycarbonylamino-2-hydroxy-pentanoic acid (4.5g) as yellowish oil. 3-tert-Butoxycarbonylamino-2-hydroxy-pentanoic acid (300mg, 1.29mmol) was combined with EDC (400mg, 2.1mmol) and HOBt (400mg, 2.6mmol). A solution of benzylamine (0.22mL) and 4-methylmoφholrne (0.5mL) in dichloromethyl (4mL) was added in one portion. The mixture was stirred at ambient temperature for 2 hours. After dilution with ethyl acetate (150mL), the solution was washed with IN aqueous HCl, water, saturated aqueous NaHCO 3 solution and brine. The resultant mixture was dried with magnesium sulfate and evaporated under vacuum to yield (S)-3-amino-2-hydroxy- pentanoic acid benzylamide (380mg) as a white solid. (S)-3-Amino-2-hydroxy-pentanoic acid benzylamide was dissolved in a mixture of TFA/dichloromethyl (1:1; 6mL), stirred for 1 hour and evaporated to dryness. (3S)-3- Amino-2-hydroxy-pentanoic acid benzylamide was obtained as the TFA salt and used without further purification. REFERENCE 8 4-(4-Methylsulfonylamino-phenyl)-4-oxo-2-benzylsulfonylmethyl -butyric acid 3-Methylene-dihydro-furan-2,5-dione (2g, 17.8mmol) and N-phenyl- methylsulfonamide (1.53g, 8.92mmol) were dissolved in anhydrous 1,2-dichloroethane. Aluminum trichloride (4.76g, 35.7mmol) was added and the mixture was stirred at 50°C for 16 hours. Following dilution with ethyl acetate (400mL), the solution was washed with IN aqueous HCl, water and brine, dried with magnesium sulfate and evaporated. The product, 4-(4-methylsulfonylaιmno-phenyl)-2-methylene-4-oxo-butyric acid (1.70g), was crystallized from ethylacetate/hexane. 4-(4-Methylsulfonylamino-phenyl)-2-methylene-4-oxo-butyric acid (800mg, 2.83mmol) was dissolved in DMF (5mL). Benzyl mercaptan (0.5mL, 4.25mmol) and DMAP (200mg, 1.6mmol) were added. The mixture was stirred at ambient temperature for 16 hours. Methanol (200mL) was added and, under vigorous stirring, a saturated aqueous solution of Oxone ® (15g, 24.4mmol) was added in one portion. Stirring was continued for 2 hours . Methanol was removed under vacuum and the aqueous residue was diluted with 1 OOmL water. The crystallized product, 4-(4-Methylsulfonylamino-phenyl)-4- oxo-2-benzylsulfonylmethyl-butyric acid (380mg), was filtered, washed with water, and dried under vacuum. REFERENCE 9 3-Biphenyl-3-yl-2-benzylsulfonylmethyl-propionic acid Sodium hydride (60% in oil, 1.36g, 34mmol) was dissolved in anhydrous ethanol (50mL) under ice cooling. After the H 2 evolution ceased, diethylmalonate (5.15mL, 34mmol) was added and stirring was continued for 30 minutes at ambient temperature. Then 3-bromobenzyl bromide (4.24g, 16.96mmol) was added and stirring was continued for 2 hours. The reaction mixture was acidified with IN aqueous HCl and extracted with ethyl acetate (3xl50mL). The combined organic layers were washed with brine, dried with magnesium sulfate and evaporated. The excess diethylmalonate was removed under high vacuum. The crude product was dissolved in ethanol (50mL) and IN aqueous NaOH (20mL) was added. After stirring for 16 hours, the mixture was acidified with IN aqueous HCl and extracted with ethyl acetate. The combined organic layers were washed with brine, dried with magnesium sulfate and evaporated. The crude monoacid was dissolved in 1,4-dioxane (20mL). Diethylamine (2.48mL, 24mmol) was added and the solution was cooled to 0°C. Formaldehyde solution (37% in water, 2.44mL) was added and stirring was continued for 24 hours at ambient temperature. After dilution with ethyl acetate (300mL), the solution was washed with water, and brine, dried with magnesium sulfate and evaporated. The crude product, 2-(3-bromo-benzyl)- acrylic acid ethyl ester, was dissolved in ethanol (20mL). Benzylmercaptan (2mL, 17mmol) and triethylamine (4mL) were added. After stirring for 16 hours, IN aqueous NaOH (50mL) was added and enough 1,4-dioxane to get a homogenous solution. The reaction mixture was warmed to 50°C for 5 hours. All organic solvents were removed under vacuum, and the aqueous residue was acidified to pH 1 with IN aqueous HCl. The product was extracted with ethyl acetate (3xl50mL). The combined organic layers were washed with brine, dried with magnesium sulfate and evaporated. The residue was dissolved in methanol (250mL) and Oxone ® (35g) was added. The reaction mixture was stirred at ambient temperature for 2 hours. Methanol was removed under vacuum. The precipitated product was filtered, washed with water, and dried under vacuum. Recrystallization from chloroform gave 3-(3-Bromo-phenyl)-2-benzylsulfonylmethyl- propionic acid (2.43g) as white solid. 3-(3-Bromo-phenyl)-2-benzylsulfonylmethyl-propionic acid (0.5g, 1.26mmol) was dissolved in toluene (20mL) and ethanol (5mL). Tetrakistriphenylphosphine palladium (146mg, 0.126mmol) was added and the mixture was stirred at ambient temperature under nitrogen for 30 minutes. Powdered potassium carbonate (870mg, 6.3mmol) and phenylboronic acid (200mg, 1.64mmol) were added, and the reaction mixture was heated at 75°C for 2 hours. After cooling, the mixture was acidified with IN aqueous HCl and extracted with ethyl acetate (3x 50mL). The combined organic layers were washed with brine, dried with magnesium sulfate and evaporated. The acid was purified by flash chromatography on silica gel (ethyl acetate/hexane; 1:1) to yield 3-biphenyl-3-yl-2- benzylsulfonylmethyl-propionic acid (0.40g). REFERENCE 10 3-Acetylsulfanyl-2-benzylsulfanylmethyl-propionic acid 2-Bromomethylacrylic acid (3.00 g, 18.1 mmol) was dissolved in methanol (lOOmL), cooled on an ice bath and treated with benzyl mercaptan. Aqueous sodium hydroxide (IN, 39.8 mL) was added dropwise and the reaction mixture was allowed to adjust to room temperature with stirring for 23 hours. Methanol was removed by rotary evaporation at reduced pressure and water (100 mL) was added to the residue, which was then washed with ether. The aqueous layer was cooled on ice and acidified to pH 2.5. The precipitated solid was isolated by filtration and dried to give 2-benzylsulfanylmethyl- acrylic acid (3.346 g, 89 %). A solution of 2-benzylsulfanylmethylacrylic acid (0.208 g) in methylene chloride (2.5 mL) was treated with thiolacetic acid and stirred at room temperature for 72 hours. The reaction mixture was diluted with ethyl acetate (50 mL) and then washed twice with water and once with saturated aqueous sodium chloride. After drying over magnesium sulfate the solvent was removed by rotary evaporation and the residue chromatographed on silica gel eluting with an ethyl acetate/hexane/acetic acid mixture to produce 3- acetylsulfanyl-2-benzylsulfanylmethyl-propionic acid (0.208 g). REFERENCE 11 (S)-2- Amino- 1 -(3-ρhenyl- \ 1.2,4] oxadiazol-5 -yl)-butan- 1 -one 3-tert-Butoxycarbonylamino-2-hydroxy-pentanoic acid (500mg, 2.14mmol) was combined with EDC (600mg, 3.14mmol), HOBt (600mg, 3.92mmol), and N-hydroxy- benzamidine (292mg, 2.14mmol). Dichloromethyl (lOmL) was added and then 4- methylmoφholine (lmL). The mixture was stirred at ambient temperature for 16 hours. After dilution with ethyl acetate (200mL), the solution was washed with water (30mL), saturated aqueous NaHCO 3 solution and brine, dried with MgSO 4 and evaporated under vacuum. The crude product was dissolved in pyridine (lOmL) and heated at 80°C for 15 hours. The pyridine was evaporated under vacuum and the residue was purified by flash chromatography on silica gel (eluent: ethyl acetate) to yield 290mg (0.83mmol). The oxadiazole (145mg, 0.41mmol) was dissolved in CH 2 C1 2 (4mL) and TFA (4mL) was added. After stirring for 1 hour, the mixture was evaporated to dryness to yield (S)-2- Amino-l-(3-phenyl-[l,2,4]oxadiazol-5-yl)-butan-l-one. REFERENCE 12 2-Ammo-l-(2-phenyl-ri.3]dithian-2-yl)-hexan-l-ol. 2-phenyl-l,3-dithiane (Aldrich) (3.79g; 19.3mmol) was mixed with dry distilled THF (20mL) under a nitrogen atmosphere. The solution was cooled to -60 °C and n-butyl lithium (1.6M in pentane, 1.56 mmol, 9.74mL) was added slowly by syringe. The reaction mixture was warmed to -20 °C and held at that temperature for 30 minutes, and then held at -10 °C for 15 minutes. The yellow solution was cooled to -78 °C and (1-Formyl- pentyl)-carbamic acid tert-butyl ester (1.6 g, 1.4 mmol, in 5 ml THF) was added rapidly (over 20 seconds) and 60 seconds later a mixture of 2mL acetic acid and 5mL THF was added rapidly. After warming to 23°C the solution was concentrated at reduced pressure. Excess 2-phenyl-l,3-dithiane was removed by its crystallization away from the desired product using a minimum of ethyl acetate in hexane. The mother liquors were concenttated and chromatographed using a hexane-ethyl acetate gradient to afford 1.7 g of {l-[Hydroxy-(2-phenyl-[l,3]dithian-2-yl)-methyl]-pentyl}-carbamic acidtert-butyl ester. (56% yield). To { l-[Hydroxy-(2-phenyl-[l,3]dithian-2-yl)-methyl]-pentyl}-carbaιnic acid tert- butyl ester (608 mg, 1.47 mmol) in 2.7mL dioxane at 10 °C was added hydrochloric acid (2.7mL, 4M in dioxane). The solution was warmed to 23 °C. After 3 hours the solution was diluted with 5 ml toluene and concenttated under reduced pressure. The gummy solid was washed with diethyl ether resulting in the hydrochloride salt of 2-amino- 1 -(2-phenyl- f 1.31 dithian-2-yl)-hexan- 1 -oL 414 mg, 82% as a free flowing solid after removal of excess ether under reduced pressure. REFERENCE 13 3-Amino-4-hvdroxo-pyrrolidme-l -carboxylic acid tert-butyl ester 6-Oxa-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (12.1g, 65.3mmol) was dissolved in a 8: 1 methanol/water mixture (108mL). Ammonium chloride (15g) and sodium azide (21.4g, 329mmol) was added and the mixture was heated at 60°C overnight. After dilution with ether (500mL), the mixture was washed with saturated aqueous NaHCO 3 (200mL) and brine (200mL), dried with MgSO and evaporated under vacuum. The crude product was dissolved in methanol (200mL). 10% Palladium on activated carbon (1.5g) was added and the mixture was stirred at ambient temperature under a hydrogen atmosphere until TLC analysis showed the disappearance of the starting material. The mixture was filtered through a pad of Celite and evaporated to dryness under vacuum. The product was purified by flash chromatography on silica gel. Eluent: 5% methanol in ethyl acetate to 20% methanol, 3% triethylamine in ethyl acetate. Yield: 4.3g of 3-amino-4-hvdroxy-pyrrolidine-l -carboxylic acid tert-butyl ester as yellowish solid. REFERENCE 14 2-Amino-2-methyl- 1 -oxazolo[4,5-b]pyridin-2-yl-propan- 1 -one 2-amino-2-methyl-l -propanol (17.8 g, 200 mmol) was dissolved in a mixture of water and 100 ml dioxane and cooled to 0°C. NaOH (8g, 200mmol) and di-t-butyl- dicarbonate (52.4g, 240mmol) were added and the reaction was allowed to warm to room temperature with stirring for 2 hours. After removing the dioxane, the residue was extracted with EtOAc, washed with brine, dried with anhydrous MgSO 4 , filtered and concentrated to yield 35g of product. A solution of oxylyl chloride (15.24g, 120mmol) in 200ml of MeCl 2 was stirred and cooled to -60°C followed by the drop wise addition of dimethylsulf oxide (19.7g, 252mmol) in 60ml of MeCl 2 . After 10 minutes, a solution of 2-bocamino-2-methyl-l- propanol (18.9g, lOOmmol) in 60ml of MeCl 2 was added drop wise at-70°C. The reaction mixture was allowed to warm to -40°C for 10 minutes followed by cooling to -70°C before the addition of a solution of triethylamine (28.28g, 280mmol) in 60 ml of MeCl 2 . The reaction mixture was allowed to warm to room temperature over a two-hour period and 40ml of saturated sodium dihydrogen phosphate was added. The organic layer was washed with brine and dried over MgSO . The solvent was removed to yield 17.3 g of aldehyde. A mixture of 2-amirio-3-hydroxy pyridine (llg, lOOmmol), ttiethylorthoformate (80ml) and p-toluenesulfonic acid (61mg) was heated at 140°C for 8 hours. Excess ttiethylorthoformate was removed under vacuum. The product was crystallized from ethyl acetate to yield 9g of pyridyloxazole; H 1 NMR (DMSO-δ): 9.26 (IH, s), 8.78 (IH, d), 8.45 (IH, d), 7.7(1H, dd); MS: 120.8 (M+l). To a stirred solution of the pyridyloxazole (2.4 g, 20mmol) in THF (100ml) was added n-BuLi (1.6M solution in 12.5ml of hexane) drop wise under N 2 at -78°C. After 1 hour, MgBr.Et 2 O (5.16g, 20mmol) was added and the reaction mixture was allowed to warm to -45°C for 1 hour before being treated with 2-boc-amino-2-methyl-propanyl- aldehyde (2.24g, 12mmol) in THF (20ml). The reaction mixture was stirred for 1 hour, quenched with saturated NHkiCl, and extracted with ethyl acetate. The organic layer was washed with brine, dried with MgSO and concenttated. The residue was purified by silica gel column chromatography to yield 2-boc-amino-2-methyl-l-(5-pyridyloxazole-2-yl)-l- propanol (1.18g); H 1 NMR (DMSO-δ): 8.5(1H, d,d, J=1.46Hz, J=4.94Hz), 8.14(1H, d,d, J1.49Hz, J=8.16Hz), 7.41(1H, d,d, J=4.7Hz, J=8.18Hz), 7.1-6.8QH, d, d), 6.53(1H, br, NH), 6.24, 6.22(1H, s,s, OH), 5.23, 5.21(1H, s,s, , 1.37(3H, s, CH3), 1.33(9H, s, 3xCH3), 1.22(3H, s, CH3); MS: 308.2 (M+l). 2-Boc-amino-2-methyl-l-(5-pyridyloxazole-2-yl)-l-propanol(156mg,0.508mmol) and MeCl 2 (5ml) were mixed and TFA (0.5ml) was added at room temperature. After stirring for 1 hour, the solvent and excess TFA were removed under vacuum to produce 2 amino-2-methyl- 1 -oxazolo[4,5-b]pyridin-2-yl-propan- 1 -one TFA salt (165mg). REFERENCE 15 2- Amino- 1 - .5-methoxymethyl- r 1.3.41 oxadiazol-2-yl , -bu tan- 1 -one (S)-(+)-2-amino-l-butanol (50g, 561mmol) in 200ml of water and 200ml dioxane was cooled to 0°C and mixed with NaOH (26.9g, 673mmol) and di-t-butyl-dicarbonate (146.96 g, 673mmol). After the addition, the reaction was allowed to warm to room temperature. The reaction mixture was stirred for 2 hours. After removing the dioxane, the residue was extracted with EtOAc, then washed with brine and dried with anhydrous MgSO , filtered and concentrated. Without further purification, the crude product (120g) was used for next step reaction. A solution of oxylyl chloride (40.39 g, 265mmol) in 700ml of MeCl 2 was stirred and cooled to -60°C. Dimethylsulfoxide (51.7 g, 663mmol) in 100 ml of MeCl 2 was added drop wise. After 10 minutes a solution of (S)-2-boc-amino-l -butanol (50 g, 265 mmol ) in 100ml of MeCl 2 was added drop wise at -70°C. The reaction mixture was allowed to warm to -40°C for 10 minutes and then cooled to -70°C again. A solution of triethylamine (74.9 g, 742mmol) in 100 ml of MeCl 2 was added. The reaction mixture was allowed to warm to room temperature over 2 hours. lOOmls of saturated sodium dihydrogen phosphate was added, and then the organic layer was washed with brine and dried over MgSO 4 . The solvent was removed to yield 45g of (l-formyl-propyl)-carbamic acid tert- butyl ester; H 1 NMR (DMSO-δ): 9.4(1H, s), 7.29(1H, br.), 3.72(1H, m), 1.69(2H, m), 1.4- 1.2(9H, s), 0.86(3H, t). A mixture of methyl methoxyacetate (52g, 500mmol), hydrazine hydrate (30ml) was heated to reflux for 8 hours. Excess hydrazine and water were removed under vacuum. The residue was extracted with n-butanol, dried with Na 2 SO 4 . Excess n-butanol was removed to yield 45g of hydrazide. A mixture of above hydrazide (45g), ttiethylorthoformate (146ml) and p- toluenesulfonic acid (61mg) was heated at 140°C for 8 hours. Excess ttiethylorthoformate was removed under vacuum. The product was purified by silica gel column chromatography to yield 4.6g of 2-methoxymethyl-l,3,4-oxadiazole; H 1 NMR (DMSO-δ): 9.21(1H, s), 4.63(2H, s), 3.27(3H, s). To a stirred solution of 2-methoxymethyl-l,3,4-oxadiazole (4.6 g, 40mmol) in THF (100ml) was added n-BuLi (1.6M solution in 25.2ml of hexane) drop wise under N 2 at - 78°C. After 1 hour, MgBr.Et 2 O (10.4g, 40.3mmol) was added and the reaction mixture was allowed to warm to -45°C for 1 hour before being treated with 2-boc-amino-propanyl aldehyde (5.28g, 28.25mmol) in THF (20ml). The reaction mixture was stirred for 1 hour, quenched with saturated NH C1, and extracted with ethyl acetate. The organic layer was washed with brine, dried with MgSO 4 and concentrated. The residue was purified by silica gel column chromatography to yield 2-boc-amino-l-(5-methoxymethyl-l ,3,4-oxadiazole-2- yl)-l-propanol (500mg); H 1 NMR (DMSO-δ): 6.7(1/2H, d, NH, diastereomeric), 6.5(1/2H, d, NH, diastereomeric), 6.2(1/2H, d, OH, diastereomeric), 6.0(1/2H, d, OH, diastereomeric), 4.83-4.79(lH, m), 4.55(2H, s), 4.05-3.5(lH, m), 3.31(3H, s), 1.9-1.4(2H, m), 1.4-1.2(9H, m), 0.85-0.81(3H, m); MS: 300.4(M-1), 302.4(M+1). 2-Boc-amino-l-(5-methoxymethyl-l,3,4-oxadiazole-2-yl)-l-propanol(500mg, 1.66mmol), and MeCl 2 (5ml) were mixed and TFA (0.5ml) was added at room temperature. After stirring for 1 hour, the solvent and excess TFA were removed under vacuum to produce 2-amino-l-(5-methoxymethyl-[1.3.41oxadiazol-2-yl)-butarι-l-one TFA salt (340mg). REFERENCE 16 2- Amino- 1 -(5-phenyl-r 1.3 ,41 oxadiazol-2-yl)- 1 -butanol A mixture of the benzylhydrazide (22.5g, 165mmol), triethylorthoformide (150ml) and p-toluenesulfonic acid (300mg) was heated at 120°C for 12 hours. Excess triethylorthoformide was removed under vacuum and the residue was purified by silica gel column chromatography to produce oxadiazole (14.5g); H 1 NMR (DMSO-δ): 9.34 (IH, s), 8.05-7.98 (2H, m), 7.68-7.55 (3H, m); MS: 147.4 (M+l). To a stirred solution of the oxadiazole (lOg, 68.5mmol) in THF (100ml) was added n-BuLi (1.6M solution in 42.8ml of hexane) drop wise under N 2 at -78°C. After 1 hour, MgBr.Et 2 O (17.69g, 68.5mmol) was added and the reaction mixture was allowed to warm to -45°C for 1 hour before being treated with 2-boc-amino-butyl-aIdehyde (7.8g, 41mmol) in THF (20ml). The reaction mixture was stirred for 1 hour, quenched with saturated NH 4 C1, and extracted with ethyl acetate. The organic layer was washed with brine, dried with MgSO 4 and concenttated. The residue was purified by silica gel column chromatography to yield 2-(2-boc-amino-l-hydroxydutyl)-5-benzyl-l,3,4-oxadiazole (9.7g); H 1 NMR (DMSO-δ): 8-7.9(2H, m), 7.8-7.7(3H, m), 6.8-6.6(lH, d,d, NH, diastereomeric), 6.4-6.1(lH, d,d, OH, diastereomeric), 5-4.4(lH, m), 1.9-1.3(2H, m), 1.3- l.l(9H, s, s), 0.84(3H, t); MS: 334.5(M+1). 2-(2-Boc-amino-l-hydroxybutyl)-5-benzyl-l,3,4-oxadiazole (505mg, 1.5mmol) and MeCl 2 (5ml) were mixed and TFA (1ml) was added at room temperature. After stirring for 1 hour, the solvent and excess TFA were removed under vacuum to produce 530mg of 2-_ amino- l-(5-phenyl-r 3,41oxadiazol-2-yl)- 1 -butanol TFA salt. REFERENCE 17 2-Amino-l-oxazolor4,5-b1pyridin-2-yl-butan-l-one A mixture of 2-amino-3-hydroxy pyridine (25g, 227mmol), ttiethylorthoformate (75ml) and p-toluenesulfonic acid (61mg) was heated at 140°C for 8 hours. Excess ttiethylorthoformate was removed under vacuum. The product was crystallized from ethyl acetate to yield 22.5g of pyridyloxazole; H 1 NMR (DMSO-δ): 9.26 (IH, s), 8.78 (IH, d), 8.45 (IH, d), 7.7(1H, dd); MS: 120.8 (M+l). Pyridyloxazole (600 mg, 5 mmol) in 30 ml THF was cooled to 0°C before the addition of isopropanyl magnesium chloride (2M in THF, 2.5 ml, 5 mmol). After stirring for 1 hour at 0°C, the aldehyde (573 mg, 3 mmol) in 20 ml THF was added. The ice bath was removed and the reaction allowed to warm to room temperature. The reaction mixture was stirred for 2 hours and quenched with saturated ammonium chloride solution. Excess THF was removed and the residue was extracted with EtOAc, washed with brine, dried with anhydrous MgSO , filtered and concentrated. The crude residue was purified by chromatography to yield 383 mg product; H 1 NMR (DMSO-δ): 8.42(1H, m), 8.18(1H, m), 7.3QH, m), 6.8, 6.6(1H, dd, d, OH, diastereomeric), 6.3, 6.02(1H, d, d, NH, diastereomeric), 4.82, 4.5(1H, m, m, diastereomeric), 1.8-1.3(2H, m), 1.2, 1.05(9H, s,s, diastereomeric), 0.89(3H, m); MS: 306.2(M-1), 308.6(M+1). To a stirred solution of the pyridyloxazole (12g, lOOmmol) in THF (300ml) was added n-BuLi (1.6M solution in 62.5ml of hexane) drop wise under N 2 at -78°C. After 1 hour, MgBr.Et 2 O (25.8g, lOOmmol) was added and the reaction mixture was allowed to warm to -45°C for 1 hour before being tteated with 2-boc-amino-butyl-aldehyde (11.46g, 60mmol) in THF (50ml). The reaction mixture was stirred for 1 hour, quenched with saturated NH t Cl, and extracted with ethyl acetate. The organic layer was washed with brine, dried with MgSO and concenttated. The residue was purified by silica gel column chromatography to yield 2-boc-amino-l-(5-pyridyloxazole-2-yl)-l-butanol (14.1g). 2-Boc-amino-l-(5-pyridyloxazole-2-yl)-l-butanol (311mg, lmmol) and MeCl 2 (5ml) were mixed and TFA (1ml) was added at room temperature. After stirring for 1 hour, the solvent and excess TFA were removed under vacuum to produce 355mg of c amino- 1 -oxazolor4,5-b1pyridin-2-yl-bu tan- 1 -one TFA salt. REFERENCE 18 2- Amino- 1 -(5-ρyridin-4-yl-[ 1.3.41oxadiazol-2-yl)-butan- 1 -one A mixture of the isonicotinic hydrazide (13.7g, lOOmmol), triethylorthoformate (60ml) and p-toluenesulfonic acid (30mg) was heated at 130°C for 12 hours. Excess triethylorthoformate was removed under vacuum. The product was crystallized from ethyl acetate to yield 14.8 g; H 1 NMR (DMSO-δ): 9.46 (IH, s), 8.8 (2H, dd), 7.9 (2H, dd). To a stirred solution of the oxadiazole (11.5g, 78.2mmol) in THF (300ml) was added 5ml HMPA and n-BuLi (1.6M solution in 48.9ml of hexane) drop wise under N 2 at -78°C. After 1 hour, MgBr.Et 2 O (20.2g, 78.2mmol) was added and the reaction mixture was allowed to warm to A5°C for 1 hour before being treated with 2-boc-amino- butylldehyde (9.7g, 50.8mmol) in THF (50ml). The reaction mixture was stirred for 1 hour, quenched with saturated NH 4 C1, and extracted with ethyl acetate. The organic layer was washed with brine, dried with MgSO 4 and concenttated. The residue was purified with silica gel column chromatography to yield 2-bocamino-l-(5-pyridin-4-yl- [l,3,4]oxadiazol-2-yl)-butan-l-ol (3.5g); H 1 NMR (DMSO-δ): 8.85-8.8(2H, m), 7.95- 7.8(2H, m), 6.66(1H, d,), 6.19(1H, d), 4.96(1H, t), 3.75-3.6(lH, m), 1.72-1.6(1H, m), 1.5- 1.35(lH, m), 1.27(9H, s), 0.87(3H, t); MS: 333.2 (M-l), 335.4 (M+l). 2-Bocamino-l-(5-pyridin-4-yl-[l,3,4]oxadiazol-2-yl)-butan-l-ol (334mg, lmmol) and MeCl 2 (5ml) were mixed and TFA (0.5ml) was added at room temperature. After stirring for 1 hour, the solvent and excess TFA were removed under vacuum to produce 350mg of 2-amino- 1 - ( 5-pyridin-4-yl- [ 1.3,41 oxadiazol-2-yl)-butan- 1 -one TFA salt. REFERENCE 19 2- Amino- 1 -(5-pyridin-3-yl- [ 1 ,3 ,41 oxadiazol-2-yl)-butan- 1 -one To a stirred solution of the 3-[l,3,4] oxadiazol-2-yl-pyridine (5g, 34mmol) in THF (100ml) was added 5ml HMPA and n-BuLi (1.6M solution in hexane, 21.25ml) drop wise under N 2 at -78°C. After 1 hour, MgBr.Et 2 O (8.77g, 34mmol) was added and the reaction mixture was allowed to warm to -45°C for 1 hour before being tteated with 2-boc-amino- butylldehyde (4.22g, 22.1mmol) in THF (20ml). The reaction mixture was stirred for 1 hour, quenched with saturated NHUC1, and extracted with ethyl acetate. The organic layer was washed with brine, dried with MgSO and concenttated. The residue was purified with silica gel column chromatography to yield 2-boc-amino-l-(5-pyridin-3-yl- [l,3,4]oxadiazol-2-yl)-butan-l-ol (1.5g); H 1 NMR (DMSO-d): 9.2-9.1(lH, d), 8.82- 8.76(1H, m), 8.4-8.3(lH, m), 7.68-7.6QH, m), 6.78, 6.65(1H, d d, NH, diastereomeric), 6.38, 6.16(1H, d,d, OH, diastereomeric), 3.8-3.6(lH, m), 1.9-1.2(2H, m), 1.3, 1.1(9H, s,s,), 0.84(3H, t); MS: 331.2 (M-l). 2-Boc-amino-l-(5-pyridin-3-yl-[l,3,4]oxadiazol-2-yl)-butan-l-ol (167mg, 0.5mmol) and MeCl 2 (5ml) were mixed and TFA (0.5ml) was added at room temperature. After stirring for 1 hour, the solvent and excess TFA were removed under vacuum to produce 180mg of 2-amino- 1 -(5-pyridin-3-yl- r 1 ,3,41 oxadiazol-2-vD-butan- 1 -one TFA salt. REFERENCE 20 2- Amino- 1 -benzooxazol-2-yl-butan- 1 -one Benzoxazole (600 mg, 5 mmol) in 20 ml THF was cooled to -5°C and isopropyl magnesium chloride ( 2 M in THF, 2.5 ml, 5 mmol ) was added. After stirring for 1 hour at -5°C, the aldehyde (561 mg, 3 mmol), prepared as in reference 15, in 10 ml THF was added. The reaction was allowed to warm to room temperature with stirring for 2 hours. The reaction was quenched with saturated ammonium chloride solution, excess THF solvent removed. The residue was extracted with EtOAc, washed with brine, dried with anhydrous MgSO , filtered and concentrated. The crude residue was purified by chromatograph to yield 688 mg product (75%); LC-MS: 305.2 (M-l), 307.0 (M+l); H J NMR (DMSO-d 6 ): 7.72-7.6 (2H, m), 7.38-7.28 (2H, m), 6.7 (d)-6.52(d) (IH, NH, diastereomeric), 6.12(d)-5.92 (d) (IH, OH, diastereomeric), 4.81(dd)-4.57(dd) (IH, CH- OH), 3.74 (IH, m), 1.9-1.6 (IH, m), 1.6-1.3 (IH, m), 1.25(s)-l.l(s) (9H, diastereomeric), 0.85 (3H, t). [l-(Benzooxazol-2-yl-hydroxy-methyl)-propyl]-carbamic acid tert-butyl ester (275mg, 0.89mmol) and MeCl 2 (5ml) were mixed and TFA (1ml) was added at room temperature. After stirring for 1 hour, the solvent and excess TFA were removed under vacuum to produce 260mg of 2-amino- 1 -benzooxazol-2-yl-butan- 1 -one TFA salt. REFERENCE 21 2-Cvclohexylmethyl-4-moφholin-4-yl-4-oxo-butyric acid A 0.05 M solution of l-(4-benzyl-2-oxo-oxazolidin-3-yl)-2-cyclohexylmethyl-4- moφholin-4-yl-butane-l,4-dione (lg) in 3:1 -THF/H 2 O was tteated at 0°C with 8 equivalents of 30% H 2 O 2 followed by 2.0 equivalents of LiOH. The resulting mixture was stirred at 0-25°C until the substrate had been consumed (approximately 1 hour). The excess peroxide was quenched at 0°C with a 10% excess of 1.5 N aqueous Na 2 SO 3 . After buffering to pH 9-10 with aqueous NaHCO 3 and evaporation of the THF, the oxazolidone chiral auxiliary was recovered by MeCl 2 extraction. The carboxylic acid was isolated by EtOAc exttaction of the acidified (pH 1 -2) aqueous phase, then recrystallized from EtOAc and hexane to yield 0.58 g of 2-cvclohexylmethyl-4-moφholin-4-yl-4-oxo-butyric acid; H 1 NMR (DMSO-δ): 12(1H, s, COOH), 3.6-3.3(8H, m), 2.8-2.3(3H, m), 1.8-1.1(1 IH, m), 0.9- 0.7(2H, m); MS: 282.2(M-1), 284.1 (M+l). REFERENCE 22 2-(2-Cvclohexyl-ethyl)-4-morpholin-4-yl-4-oxo-butyric acid (S)-(-)-4-Benzyl-2-oxazolidinone (5g, 28.2mmol) was dissolved in THF (lOOmL) and cooled to -78°C under nitrogen. A 2.5M solution of n-butyllithium in hexane (12.4mL) was added with a syringe and the mixture was stirred for 30min. 4-Cyclohexyl- butyryl chloride (5.85g, 3 lmmol) was added at -78°C. The mixture was allowed to warm to 0°C over two hours. IN HCl (50mL) was added and the product was extracted with ethyl acetate (3xl00mL). The combined organic layers were washed with saturated aqueous NaHCO 3 (200mL) and brine (200mL), dried with MgSO and evaporated under vacuum. The product was recrystallized from hexane/ether and obtained as a white solid (5.6g). A solution of diisopropylamine (1.92mL, 13.68mmol) in dry THF (50mL) was cooled to -20°C. A 2.5M solution of n-butyllithium in hexane (4.4mL) was added with a syringe. The mixture was stirred for 30min and then cooled to -78°C. A solution of 4- benzyl-3-(4-cyclohexyl-butyryl)-oxazolidin-2-one (3g, 9.12mmol) in THF (lOmL) was added slowly over 3min. Stirring was continued for 30min, then a solution of 2-Bromo-l- moφholin-4-yl-ethanone (2.28g, 10.94mmol) in THF (4mL) was added over 3min. The mixture was allowed to come to room temperature over 5h. IN HCl (50mL) was added and the product was extracted with ethyl acetate (3xl00mL). The combined organic layers were washed with saturated aqueous NaHCO 3 (200mL) and brine (200mL), dried with MgSO and evaporated under vacuum. The product (l-(4-benzyl-2-oxo-oxazolidin-3-yl)- 2-(2-cyclohexyl-ethyl)-4-moφholin-4-yl-butane-l,4-dione) was obtained after purification by flash chromatography as a single diastereomer (2.5g). 1H NMR: (CDC1 3 ) 7.35-7.22 (m, 5H), 4.69-4.62 (m, IH), 4.28-4.10 (m, 3H), 3.76-3.46 (m, 8H), 3.37 (d, J=13.6Hz, IH), 2.91 (ddd, J=16.4Hz, J=13Hz, J=3Hz, IH), 2.76 (ddd, J=13.5Hz, J=llHz, J=3Hz, IH), 2.51 (dt, J=13.6Hz, J=3Hz, IH), 1.76-0.80 (m, 15H). MS: (M+H) + 457. l-(4-Benzyl-2-oxo-oxazolidin-3-yl)-2-(2-cyclohexyl-ethyl)-4-moφholin-4-yl- butane-l,4-dione (2.5g, 5.48mmol) was dissolved in a 3:l-THF/H 2 O mixture (50mL) and cooled to 0°C. H 2 O 2 (5mL) was added followed by lithium hydroxyde monohydrate (462mg, 11 mmol). The mixture was stirred at 0°C for 30min. Excess peroxide was quenched with 1.5N Na 2 SO 3 solution and the THF was evaporated under vacuum. The chiral auxiliary was removed by exttaction with diethyl ether. After acidification to pH 1 the product was isolated by extraction with ethyl acetate. The combined organic layers were washed with saturated aqueous NaHCO 3 (200mL) and brine (200mL), dried with MgS0 and evaporated under vacuum. The crude acid ((2R)-2-(2-Cyclohexyl-ethyl)-4- moφholin-4-yl-4-oxo-butyric acid) was used for coupling (EDC) and oxidation (Dess- Martin) as described in the examples, infra. (2R)-l-((4S)-4-Benzyl-2-oxo-oxazolidin-3-yl)-2-cvclohexylmethyl-4-morpholin-4- yl-butane- 1 ,4-dione was prepared by the same procedure as described for reference 22.4- Cyclohexyl-butyryl chloride was substituted by 3-cyclohexyl-propionyl chloride. ! H NMR: (DMSO) 7.35-7.22 (m, 5H), 4.63-4.56 (m, IH), 4.28 (t, J=8.5Hz, IH), 4.17-4.06 (m, 2H), 3.70-3.35 (m, 8H), 2.94 (d, J=13.2Hz, IH), 2.82 (dd, J=13.2Hz, J=8Hz, IH), 2.72 (dd, J=16Hz, J=10.4Hz, IH), 2.51 (dd, J=16Hz, J=3.2Hz, IH), 1.75-0.75 (m, 13H); MS: (M+H) + 443. REFERENCE 23 N-Isopropyl-2-benzylsulfonylmethyl-succinamic acid To a stirring mixture of itacconic anhydride (1.1209g, lOmmol) in 10 ml of methylene chloride at 0°C was added drop wise isopropyl amine (0.85ml, lOmmol). The reaction was stirred at room temperature for 1 hour and the solvent was removed under reduced pressure to give 2-(isopropylcarbamoyl-methyl)-acrylic acid. The residue was dissolved in 10 ml of DMF, then benzyl mercaptan (1.17g, lO.Ommol) and DMAP (122mg, lmmol) were added and the reaction was stirred at room temperature for overnight. The mixture containing 2-benzylsulfanylmethyl-N-isopropyl-succinamic acid was cooled to 0°C and oxone® (4.9182g, 8mmol) in 20 ml of water was added and stirred for 2 hours at room temperature. More oxone® was added and the reaction was stirred at room temperature for 18 hours. The reaction was filtered and the white solid was washed with water, ether and dried under high vacuum to give 1.0 grams of N-isopropyl-2-benzylsulfonylmethyl- succinamic acid, which was used without further purification; LCMS retention time 2:32minutes: MS+1 (328.1). REFERENCE 24 4-(4-Methyl-piperazin- 1 -yl)-4-oxo-2-benzylsulfonylmethyl-butyric acid To a stirring mixture of itacconic anhydride 1.1209g, lOmmol) in 10 ml of methylene chloride at 0°C was added drop wise methyl piperizine (l.Og, lOmmol). The reaction was stirred at room temperature for 1 hour and the solvent was removed under reduced pressure to give compound 2-[2-(4-methyl-piperazin-l-yl)-2-oxo-ethyl]-acrylic acid. The residue was dissolved in 10 ml of DMF, then benzyl mercaptan (1.17g, lO.Ommol) and DMAP (122mg, lmmol) were added and heated to 50-60°C until reaction turned clear then the reaction was stirred at room temperature for overnight. Another 0.59 ml of benzyl mercapton (5mmol) was added and the reaction was stirred overnight at room temperature. The mixture containing compound 2-benzylsulfanylmethyl-4-(4-methyl- piperazrn-l-yl)-4-oxo-butyric acid was cooled to 0°C and oxone® (6.1378g, lOmmol) in 20 ml of water was added and stirred for overnight at room temperature. More oxone® was added and the reaction was stirred at room temperature for 2 hours. The reaction was filtered and the product was in the aqueous phase and was purified on HPLC to give 0.2477 gram of pure 4- ( 4-methyl-piperazin- 1 -yl)-4-oxo-2-benzylsulfonylmethyl-butyric acid; LCMS retention time: 1.72 minutes; M+l (369.3). REFERENCE 25 2-(2-Morpholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid Reference 25 was synthesized as described in the following reaction protocol: 2-(2-Moφholin-4-yl-2-oxo-ethyl)-malonic acid diethyl ester (1) To a solution of n-tetta butyl ammonium hydrogen sulfate (1.18g, 3.48 mmol) and NaOH (560 mg, 13.9 mmol) in water (8 ml) was added a solution of 4-(2-bromoacetyl moφholine) (1.45g, 6.97 mmol) and diethyl malonate (1.34g, 8.36 mmol) in DCM (8 ml). The mixture was stirred at room temperature for 3 hours, diluted with water (30 ml) and extracted with DCM (2x30 ml). The organic layer was dried (MgSO 4 ) and concenttated in vacuum. The residue was purified by chromatography (silica) eluting with 1:2 v/v ethyl acetate - heptane to give 2-(2-moφholin-4-yl-2-oxo-ethyl)-malonic acid diethyl ester as a colorless oil (1.19 g, 59%); X H MR (CDC1 3 ) 4.25 (m, 4H), 4.0 (t, J=7.2Hz, lH), 3.8-3.45 (m, 8H), 3.0 (d, J=7.4Hz, 2H), 1.3 (t, J=7.1Hz, 6H). 2-(2-Moφholin-4-yl-2-oxo-ethyl)-2-(3-phenyl-allyl)-malonic acid diethyl ester (2) To a mixture of Pd(OAc) 2 (17.5 mg, 0.078 mmol) and PPh 3 (40.9 mg, 0.156mmol) in dry THF (2ml) under N 2 , cmnamyl alcohol (105.1 mg, 0.78 mmol) was added followed by a solution of 2-(2-moφholin-4-yl-2-oxo-ethyl)-malonic acid diethyl ester (250 mg, 0.87 mmol) andNaH (17.4 mg, 0.43 mmol) in dry THF (3 ml). BF 3 (IM in THF, 1ml, 1 mmol) was then added and the yellow solution was stirred at room temperature for 6.5 hours. The mixture was diluted with ethyl acetate (50 ml) and washed with IN HCl (10 ml) and brine (2 x 20 ml). The organic layer was dried (MgSO 4 ), concenttated in vacuum and purified by chromatography eluting with 1:1 v/v ethyl acetate - heptane mixture to give 2-(2- moφholin-4-yl-2-oxo-ethyl)-2-(3-phenyl-allyl)-malonic acid diethyl ester as a thick, yellow oil (266.5 mg, 85%); 1H NMR (CDC1 3 ) 7.25 (m, 5H), 6.40 (d, J=15.6Hz, IH), 6.1 (dt, J=15.8, 7.7Hz), 4.2 (q, J=7. IHz, 4H), 3.6 (m, 6H), 3.45 (m, 2H), 3.05 (d, J=7.6Hz, 2H), 3.0 (s, 2H), 1.25 (t, J=7.1Hz, 6H). MS: 404 (MH*) 2-(2-Morpholin-4-yl-2-oxo-ethyl)-2-(3-phenyl-propyl)-malonic acid diethyl ester (3) A solution of 2-(2-moφholin-4-yl-2-oxo-ethyl)-2-(3-phenyl-allyl)-malonic acid diethyl ester (257 mg, 0.637 mmol) in EtOH (15 ml) was hydrogenated over Pd/C at 55 Psi for 7.5 hrs. The catalyst filtered off over a pad of Celite and the filtrate evaporated under vacuum to give 2-(2-moφholin-4-yl-2-oxo-ethyl)-2-(3-phenyl-propyl)-malonic acid diethyl ester as a light yellow oil (260 mg); 1H NMR (CDC1 3 ) 7.4-7.1 (m, 5H), 4.20 (q, J=7.1Hz, 4H), 3.7-3.4 (m, 8H), 3.0 (s, 2H), 2.6 (t, J=7.6Hz, 2H), 2.2 (m, 2H), 2.55 (m, 2H), 1.20 (t, J=7.1Hz, 6H). MS: 406 (MH + ). 2-(2-Moφholin-4-yl-2-oxo-ethyl)-2-(3-phenyl-propyl)-malonic cid monoethyl ester (4) To a solution of 2-(2-moφholin-4-yl-2-oxo-ethyl)-2-(3-phenyl-propyl)-malonic acid diethyl ester (934 mg, 2.3 mmol) in a 2:1 mixture of ethanol and water (12 ml) LiOH.H 2 O (193.3 mg, 4.61 mmol) was added and heated at 40 °C for 19 hrs. Ethanol was evaporated under reduced pressure, the residual aqueous mixture was acidified to pH 1 and extracted with methylene chloride (2x40 ml). The organic extract was dried with MgSO and evaporated under reduced pressure to give 2-(2-moφholm-4-yl-2-oxo-ethvD-2-(3- phenyl-propyD-malonic acid monoethyl ester as a thick, yellow oil (831 mg); 1H NMR (CDCI 3 ) 7.4-7.1 (m, 6H), 4.25 (q, J=7.1Hz, 2H), 3.8-3.4 (m, 8H), 3.20 (d, J=16.4Hz, IH), 2.9 (d, J=16.4Hz, IH), 2.6 (m, 2H), 2.1-1.8 (m, 4H), 1.25 (t, J=7.1Hz, 3H). MS : 378 (MH*). 2-(2-Morpholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid ethyl ester (5) A Solution of 2-(2-moφholin-4-yl-2-oxo-ethyl)-2-(3-phenyl-propyl)-malonic acid monoethyl ester (809 mg, 2.14 mmol) in toluene (25 ml) was heated under reflux for 23 hours. The colorless solution was concentrated under reduced pressure, the residue was taken up in diethyl ether (50 ml), washed with saturated NaHCO 3 and dried over MgSO 4 . The solvent was evaporated under reduced pressure to give 2-(2-morpholm-4-yl-2-oxo- ethyl)-5-phenyl-pentanoic acid ethyl ester as yellow oil (617 mg); 1H NMR (CDC1 3 ) 7.3- 7.1 (m, 5H), 4.2 (m, 2H), 3.8-3.4 (m, 8H), 3.0 (m ,1H), 2.75 (dd, J=15.9, 9.4Hz, IH), 2.65 (m, 2H), 2.35 (dd, J=15.9, 5.1Hz, IH), 1.8-1.55 (m, 4H), 1.29 (t, J=7.1Hz, 3H). MS : 334 (MH + ). 2-(2-Moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid (6) To a solution of 2-(2-moφholin-4-yl-2-oxθ-ethyl)-5-phenyl-pentanoic acid ethyl ester (604 mg, 1.81 mmol) in a 2:1 mixture of MeOH-H 2 O (12 ml) LiOH.H 2 O (228 mg, 5.43 mmol) was added and stirred overnight at room temperature. Ethanol was removed under reduced pressure, residue diluted with water (40 ml) and washed with ether. The aqueous layer was acidified to pHl with IN HCl and extracted with diethyl ether (3x 25 ml). The combined organic exttacts were dried with MgSO and concentrated under reduced pressure to give 2-(2-moφholm-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid as a white solid (492 mg); *H NMR (CDCI 3 ) 8.0-7.5 (IH), 7.4-7.1 (m, 5H), 3.8-3.4 (m, 8H), 3.0 (m, IH), 2.8 (dd, J=16.4, 9.6Hz, IH), 2.65 (t, J=7.2Hz, 2H), 2.40 (dd, J=16.4, 4.3Hz, IH), 1.9-1.5 (m, 4H). MS : 306 (MH ). REFERENCE 26 2-Amino-l-(5-phenyl-ri,2,41oxadiazol-3-yl)-butan-l-ol Reference 26 was synthesized as described in the following reaction protocol: Microwave, 150 C diglyme (5) (4) { l-rHvdroxy-(N-hydroxycarba_ midoyl)-methyl]-propyU-carbamic acid tert-butyl ester (2) A solution of (2-cyano-l-ethyl-2-hydroxy-ethyl)-carbamic acid tert-butyl ester (9.53g, 44 mmol) in methanol (80 ml) was cooled to 0°C and tteated successively with hydroxylamine hydrochloride (3.05, 44 mmol) in methanol (80 ml) and 25% sodium methoxide solution in methanol (10.2 ml). Stirred at 0°C for 5 minutes, cold bath removed and the reaction mixture stirred at room temperature for 5 hours. Methanol evaporated off under reduced pressure, crude partitioned between ethyl acetate and water. Organic layer separated, dried (MgSO ) and evaporated under reduced pressure to give yellow oil. Purified by mplc, eluting with a mixture of ethyl acetate - heptane to give the title compound as white solid (3.5 g); MS: M(H + ) 248. { l-rHydroxy-(N-benzoyloxycarbamimidoyl)-methyll-propyl|-carbamic acid tert-butyl ester (3) A solution of { l-[hydroxy-(N-hydroxycarbamimidoyl)-methyl]-propyl}-carbamic acid tert-butyl ester (2) (2.5g, 10 mmol) in dichloromethyl (125 ml) was tteated with benzoic acid (1.36 g, 11 mmol), EDCI (2.14 g, llmmol), HOBT (1.37 g, 10 mmol) and triethylamine (1.35 ml, 11 mmol) and stirred at room temperature overnight. Reaction mixture was washed with saturated sodium bicarbonate solution and then water and dried over Νa 2 SO 4 . Solvent evaporated under reduced pressure, crude purified by mplc eluting with 1% triethylamine in 2:3 v/v ethyl acetate and heptane mixture to give yellow solid (850 mg); MS: MH + 352. 2-Amino-l-(5-phenyl-[l,2,4]oxadiazol-3-yl)-butan-l-ol (5) A solution of (3) (1.5g, 4.3 mmol) in diglyme was heated at 150°C in a microwave (Smitli Creator, S00219) for 40 minutes. Solvent evaporated under vacuum in Genevac Evaporator at 80°C for 3hours to give a brown solid. This was taken in dichloromethyl (40 ml) and tteated with ttifluoroacetic acid at room temperature for 2 hours. Solvent evaporated to dryness under reduced pressure, crude taken in water, washed with DCM, aqueous layer basified with IM NaOH solution and extracted with dichloromethyl. Organic layer dried over Na 2 SO 4 to give pale brown solid (300mg); 1 HNMR (CDC1 3 ) 8.14- 8.10 (m, 2H), 7.59-7.47 (m, 3H), 4.83 & 4.65 (d, J= 5Hz, IH), 3.18-3.05 (2m, IH), 1.71- m, 2H), 1.05-0.97 (dt, J= 7.2Hz, 3H). REFERENCE 27 3-Benzylsulfonyl-2-(tetrahvdro-pyran-4-yloxymethyl)-propionic acid (27a) -(Propane-l-sulfonyl)-2-(tetrahvdro-pyran-4-yloxymethyl)-propionic acid (27b) Compounds 27a and 27b were synthesized according to the following protocol: 2-(Tettahvdro-pyran-4-yloxymethyl)-acrylic acid ethyl ester (1) NaH added to a solution of 4-hydroxy tetrahydropyran (5g, 49 mmol) in THF (40ml) stirred at room temperature for 30 minutes. A solution of ethyl 2-(bromomethyl) acrylate (9.6 g, 49 mmol) in THF (30 ml) was added and stirred at room temperature overnight. Reaction mixture cooled in ice, quenched with saturated NH CI solution and exttacted with ethyl acetate. Organic exttacts dried, (Na SO ) and purified by mplc eluting with 1 :9 to 2:8 v/v ethyl acetate - heptane mixture to give the title compound as yellow oil (6.56g, 61%). MS: MH" 215; LCMS retention time 3.29 minutes. 3-Benzylsulfanyl-2-(tettalιvdro-pyran-4-yloxymethyl)-propionic acid ethyl ester (2a) A suspension of 2-(tetrahydro-pyran-4-yloxymethyl)-acrylic acid ethyl ester (2.2g, 10.2 mmol) in ethanol (100 ml) was tteated with a solution of NaHCO 3 (0.86g, 10.2 mmol) in water ml (10ml) and benzyl mercapton (1.21 ml, 10.2 mmol) at room temperature overnight. Ethanol evaporated off under reduced pressure, crude partitioned between ethyl acetate and water, organic layer separated and purified by mplc eluting with 1 :9 to 2: 8 v/v ethyl acetate -heptane mixture to give the title compound as pale yellow oil (1.27g). MS: 339 (MH + ); LCMS (Protocol B) retention time 4.3 minutes. By using ethylmercapton 3-ethylsulfanyl-2-(tetrahydro-pyran-4-yloxymethyl)- propionic acid ethyl ester (2b) was similarly prepared; MS : 281 (MH 1" ); LCMS retention time 3.9 minutes. 3-Benzylsulfanyl-2-(tettahvdro-pyran-4-yloxymethyl)-propionic acid (3a) A solution of 3-benzylsulfanyl-2-(tetrahydro-pyran-4-yloxymethyl)-propionic acid ethyl ester (1.27g) in ethanol (30ml) was treated with 2N NaOH (9.4 ml) overnight. Usual water work up gave the title compound as white solid; MS: 333 (M+Na), 311 (M+l); LCMS retention time 3.7 minutes. 3-Ethylsulfanyl-2-(tetrahydro-pyran-4-yloxymethyl)-propionic acid (3b) was similarly prepared by using 3-ethylsulfanyl-2-(tetrahydro-pyran-4-yloxymethyl)-propionic acid ethyl ester. 3-Benzylsulfonyl-2-(tetrahvdro-pyran-4-yloxymethyl)-proρionic acid (27a) A solution of 3-Benzylsulfanyl-2-(tetrahydro-pyran-4-yloxymethyl)-propionic acid (1.16g, 3.7 mmol) in a mixture of MeOH (10 ml) and water (30 ml) was treated oxone (3.5 g, 5.6 mmol) overnight. Methanol evaporated off under reduced pressure, aqueous layer extracted with ethyl acetate, dried (Na 2 SO ) and evaporated under reduced pressure to give the title compound as white solid (1.36 g); MS: 365 (M+Na), 343 (MH 1" }; LCMS retention time 3.1 minutes. 3-ethylsulfonyl-2-(tettahydro-pyran-4-yloxymethyl)-propionic acid (27b) was similarly prepared from 3-ethylsulfanyl-2-(tetrahydro-pyran-4-yloxymethyl)-propionic acid; MS: 303 (M+Na), 281 (MH 1" ); LCMS retention time 2.3 minutes. REFERENCE 28 4-Mθφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (28a); -(2-Methyl-propane- 1 -sulfonylmethyl)-4-moφholm-4-yl-4-oxo-butyric acid (28b) ; -Cvcloρropylmethylsulfonylmethyl-4-moφholin-4-yl-4-oxo-butyric acid (28c); and -(2-Difluoromethoxy-benzylsulfonylmethyl)-4-morpholin-4-yl-4-oxo-butyric acid (28d (28a) (28b) (28c) (28d) 4-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (28a) -(2-Methyl-propane-l-sulfonylmethyl)-4-morpholin-4-yl-4-oxo-butyric acid (28b) 2-Cyclopropylmethylsulfonylmethyl-4-moφholin-4-yl-4-oxo-butyric acid (28c) -(2-Difluoromethoxy-benzylsulfonylmethyl)-4-morpholin-4-yl-4-oxo-butyric acid (28d) Compounds 28a, b, c and d were synthesized accordmg to the following protocol: DMF, 20h, r.t. Synthesis of 2-(2-morpholin-4-yl-2-oxo-ethyl)-acrylic acid (1) Moφholine (20mL, 228.6 mmol) was slowly added to a stirring solution of itaconic anhydride (25. Ig, 228.6 mmol) suspended in dichloromethyl at 0°C. The reaction mixture was allowed to slowly warm to room temperature. Upon completion (LCMS), volatiles were removed by vacuum under reduced pressure. Crude yield: 44.96g, 99%. Product was used without further purification. Synthesis of 2-Acetylsulfanylmethyl-4-moφholin-4-yl-4-oxo-butyric acid (2) 2-(2-moφholin-4-yl-2-oxo-ethyl)-acrylic acid (55.19g, 277.0 mmol) was dissolved in 120mL DMF and set to stir at room temperature. Potassium thioacetate (25g, 219.0 mmol) was added in one portion, and the reaction mixture was allowed to stir at ambient temperature for 20 hours. Upon completion (LCMS), DMF was removed by vacuum under reduced pressure. Crude Yield: 75g. Percent Purity (LCMS): 40%. The crude product was used without further purification. Synthesis of 4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (28a) 4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (8.078g, 29.37 mmol) was dissolved in lOOmL dry EtOH and set to stir at room temperature. NaOH pellets (3.52g, 88.0 mmol) were added in one portion, and the reaction mixture was allowed to stir for 10 minutes. Benzyl bromide (3.18mL, 26.7 mmol) was then added, and the reaction mixture was allowed to stir at ambient temperature for 20 hours. Upon completion (LCMS), the reaction mixture was diluted with water and the pH was lowered to ~pH2. The reaction mixture was then washed 3x with EtOAc. The organic phase was concenttated in vacuo and then diluted with 200mL aqueous MeOH. Oxone® (10.78g, 16.58 mmol) was added in one portion and the reaction was stirred at room temperature for 4 hours. Conversion of sulfide to sulfone was monitored via LCMS. Upon completion, reaction was quenched by the addition of sodium thiosulfate. Salts were filtered and the reaction mixture was washed 3X with ethyl acetate and dried over sodium sulfate. The organics were evaporated by vacuum under reduced pressure. The crude solid was crystallized from EtOAc. Yield 1.3g Percent Purity (NMR): 99%. m/z (LCMS) M 1" 356.01. δ H 12.6 (1 H, br s), 7.4 (5 H, m), 4.5 (2 H, s), 3.5 (4 H, m), 3.5 (1 H, m), 3.4 (4H, m), 3.2 (2 H, d), 2.75 (2 H, d). Synthesis of 2-(2-Methyl-propane- 1 -sulf onylmethyl)-4-morpholin-4-yl-4-oxo-bu tyric acid (28b) 4-Mθφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (10.90g, 40.15 mmol) was dissolved in lOOmL dry EtOH and set to stir at room temperature. NaOH pellets (4.81g, 120.45 mmol) were added in one portion, and the reaction mixture was allowed to stir for 10 minutes. l-Bromo-2-methyl propane (5.0g, 36.49 mmol) was then added, and the reaction mixture was allowed to stir at ambient temperature for 20 hours. Upon completion (LCMS), the reaction mixture was diluted with water and the pH was lowered to ~pH2. The reaction mixture was then washed 3x with EtOAc. The organic phase was concentrated in vacuo and then diluted with 200mL aqueous MeOH. Oxone (10.02g, 14.57 mmol) was added in one portion and the reaction was stirred at room temperature for 4 hours. Conversion of sulfide to sulfone was monitored via LCMS. Upon completion, reaction was quenched by the addition of sodium thiosulfate. Salts were filtered, and the reaction mixture was washed 3X with ethyl acetate and dried over sodium sulfate. The organics were evaporated by vacuum under reduced pressure. Product was purified via HPLC. Yield: l.lg, 23.1%. m/z (LCMS) M + 322.01, R f = 2.03. δ H 12.6 (l H,br s), 3.5 (4 H, m), 3.5 (1 H, m), 3.4 (4 H, m), 3.25 (2 H, d), 3.0 (2 H, m), 2.9 (2 H, d), 2.4 (1 H, m), 1.3 (6H, d d). Synthesis of 2-Cvclopropylmethylsulfonylmeιhyl-4-morpholin-4-yl-4-oxo-butyric acid (28c) 4-Moφholin-4-yl-4-oxo-2-benzylsulfony_methyl-butyric acid (11.16g, 40.74 mmol) was dissolved in lOOmL dry EtOH and set to stir at room temperature. NaOH pellets (4.81g, 120.25 mmol) were added in one portion, and the reaction mixture was allowed to stir for 10 min. Bromomethylcyclopropane (5.0g, 37.04 mmol) was then added, and the reaction mixture was allowed to stir at ambient temperature for 20 hours. Upon completion (LCMS), the reaction mixture was diluted with water and the pH was lowered to ~pH2. The reaction mixture was then washed 3x with EtOAc. The organic phase was concenttated in vacuo and then diluted with 200mL aqueous MeOH. Oxone (15.6g, 24.0 mmol) was added in one portion and the reaction was stirred at room temperature for 4h. Conversion of sulfide to sulfone was monitored via LCMS. Upon completion, reaction was quenched by the addition of sodium thiosulfate. Salts were filtered, and the reaction mixture was washed 3X with ethyl acetate and dried over sodium sulfate. The organics were evaporated by vacuum under reduced pressure. Product was purified via HPLC. Yield: 1.2g, 15.1%. m/z (LCMS) M + 320.1, R f = 1.84. δ H 12.6 (1 H,brs), 3.5 (4 H, m), 3.5 (1 H, m), 3.4 (4 H, m), 3.25 (2 H, d), 3.0 (2 H, m), 2.9 (2 H, d), 2.4 (1 H, m), 1.1 (1 H, m), 0.62 (2 H, q), 0.38 (2 H, q). Synthesis of 2-(2-Difluoromethoxy-benzylsulfonylmethyl)-4-morpholin-4-yl-4-oxo- butyric acid (28d) 4-MoφhoIin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (1.27g, 4.64 mmol) was dissolved in 50mL dry EtOH and set to stir at room temperature. NaOH pellets (556mg, 13.92 mmol) were added in one portion, and the reaction mixture was allowed to stir for 10 min. 2-(Difluoromethoxy)-benzyl bromide (1.00g, 4.219 mmol) was then added, and the reaction mixture was allowed to stir at ambient temperature for 20h. Upon completion (LCMS), the reaction mixture was diluted with water and the pH was lowered to ~2. The reaction mixture was then washed 3x with EtOAc. The organic phase was concenttated in vacuo and then diluted with lOOmL aqueous MeOH. Oxone (1.58g, 2.43 mmol) was added in one portion and the reaction was stirred at room temperature for 4h. Conversion of sulfide to sulfone was monitored via LCMS. Upon completion, reaction was quenched by the addition of sodium thiosulfate. Salts were filtered, and the reaction mixture was washed 3X with ethyl acetate and dried over sodium sulfate. The organics were evaporated by vacuum under reduced pressure. Product was purified via HPLC. Yield: 195mg, 19.0%. m/z (LCMS) M + 422.1. R f = 2.42. δ H 12.6 (1 H, br s), 7.6—7.2 (4 H, m), 7.19 (1 H, s) 4.5 (2 H, s), 3.5 (4 H, m), 3.5 (1 H, m), 3.4 (4 H, m), 3.2 (2 H, d), 2.75 (2 H, d). REFERENCE 29 ( " R)-2-((S)- 1 -Hvdroxy-2-morpholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid (5a) (RV5-(2-Difluoromethoxy-phenyl)-2-((S)-l-hvdroxy-2-moφholin-4-yl-2-oxo-ethyl)- pentanoic acid (5b) t / RV2-((S)-l-Fluoro-2-morpholin-4-yl-2-oxo-ethyl)-5-phenyl-ρentanoic acid (5c) RV5-(2-Difluoromethoxy-phenyl)-2-..S')-l-fluoro-2-moφholin-4-yl-2-oxo-ethyl)- pentanoic acid (5d) (5a) R =H (5c) R =H (5b) R = OCHF 2 (5d) R = OCHF 2 Compounds 5a, 5b, 5c and 5d were prepared according to the following reaction protocol: (S)-3-Acetoxy-4-morpholin-4-yl-4-oxo-butyric acid (la) & (S)-2-Acetoxy-4-morpholm-4-yl-4-oxo-butyric acid . lb . Moφholine (14.48 ml) and Triethylamine (23.14 ml, 166 mmol) were added to an ice-cold solution of acetic acid (S)-2,5-dioxo-tettahydro-furan-3-yl ester (25g, 158.12 mmol) in dry THF (600 ml) and the solution was stirred at room temperature over the week-end. Solvent was evaporated under reduced pressure, residue diluted with water, acidified to pH 2 with IN HCl and extracted with ethyl acetate. Combined organic extracts were dried over MgSO 4 and evaporated under reduced pressure to give a mixture of (S)-3- acetoxy-4-moφholin-4-yl-4-oxo-butyric acid and 2-acetoxy-4-morpholm-4-yl-4-oxo- butyric acid (14g) as colorless oil. MS: 246 (MH 1 ). (S)-3-Hvdroxy-4-moφholin-4-yl-4-oxo-butyric acid methyl ester (2a) To a mixture of (S)-3-acetoxy-4-moφholin-4-yl-4-oxo-butyric acid and 2-Acetoxy- 4-moφholin-4-yl-4-oxo-butyric acid (llg, 44.8 mmol) in dry methanol (30 ml) HCl in dioxane (4M, 7.3 ml, 29.16 mmol) was added and stirred at room temperature for 5 hrs. The reaction mixture was neutralized with solid NaHCO 3 , filtered through a mixture of Celite/Na 2 SO (1 : 1) and concentrated under reduced pressure to give a mixture of (S)-3- Hydroxy-4-moφholin-4-yl-4-oxo-butyric acid methyl ester and (S)-2-Hydroxy-4- moφholin-4-yl-4-oxo-butyric acid methyl ester. Column chromatography on silica eluting with a mixture of ethyl acetate and methylene chloride gave (S)-3-Hydroxy-4-_noφholm-4- yl-4-oxo-butyric acid methyl ester, (6 g) as white solid; ! H NMR (CDC1 3 ) δ 2.62 (d, J=8Hz, 2H), 3.78-3.44 (m, 1 IH), 3.76 (d, J=9Hz, IH), 4.8-4.73 (m, IH); MS: 218(MH + ). (E)-(R)-2-((SVl-Hvdroxy-2-morpholin-4-yl-2-oxo-ethyl)-5-phenyl -pent-4-enoic acid methyl ester (3a) Lithium hexamethyldisilazide (IM in THF, 14.5 ml, 14.5 mmol) was added to a solution of (S)-3-Hydroxy-4-moφholm-4-yl-4-oxo-butyric acid methyl ester (1.5g, 6.9 rnmol) in dry THF (15 ml) at -78° C under N and stirred for 30 min. Cinnamyl bromide (1.6g, 7.32 mmol) was then added, the reaction mixture stirred at -78 °C for 2 hrs, warmed up to room temperature and stirred overnight at room temperature. The reaction was quenched with saturated ammonium chloride solution, adjusted the pH to 6 with IN HCl and exttacted with ethyl acetate. Combined ethyl acetate exttacts were dried over MgSO and concenttated under reduced pressure to give pale brown solid. Column chromatography on silica eluting with a mixture of ethyl acetate and methylene chloride gave the title compound as pale, yellow solid (1.15 g). (E)-(R)-5-(2-Difluoromethoxy-phenyl)-2-((S)-l-hvdroxy-2-morpholin-4-yl-2-oxo- ethyD-pent-4-enoic acid methyl ester (3b) Similarly prepared accordmg to the procedure above but replacing cinnamyl bromide withl- ((E)-3-Bromo-propenyl)-2-difluoromethoxy-benzene. (2R,3S)-2-Benzyl-3-hvdroxy-4-moφholin-4-yl-4-oxo-butyric acid methyl ester (3c) Similarly prepared according to the procedure above but replacing cinnamyl bromide with benzyl bromide. (R)-2-((S)-l-Hvdroxy-2-morpholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid methyl ester (4a) A solution of (Ε)-(R)-2-((S)-l-Hydroxy-2-moφholin-4-yl-2-oxo-ethyl)-5-phenyl- pent-4-enoic acid methyl ester (1.55g, 4.65 mmol) in methanol (15 ml) was hydrogenated at 50 psi over Pd/C for 4 hrs. The catalyst was removed by filtration through celite and the filtrate concentrated under reduced pressure to give (R)-2-((S)-l-Hydroxy-2-moφholin-4- yl-2-oxo-ethyl)-5-ρhenyl-pentanoic acid methyl ester as pale, brown solid (1.45 g); 1H NMR (CDC1 3 ) δ 1.90-1.65 (m, 4H), 2.62-2.75 (m, 3H), 3.75-3.40 (m, IIH), 4.0 (d, J=15Hz, IH), 4.47-4.4.39 (m, IH), 7.38-7.15 (m, 5H); MS: 336(M + ). (-RV5-(2-Difluoromethoxy-phenyl)-2-((SVl-hydroxy-2-moφholin-4-yl-2-oxo-ethyl)- pentanoic acid methyl ester (4b) Similarly prepared according to the procedure above but using (E)-(R)-5-(2- Difluoromethoxy-phenyl)-2-((S)-l-hydroxy-2-moφholin-4-yl-2-oxo-ethyl)-pent-4-enoic acidmethyl ester; HNMR (CDC1 3 ) δ 1.93-1.58 (m, 4H), 2.78-2.58 (m, 3H), 3.80-3.42 (m, IIH), 4.03 (m, IH), 4.44 (m, IH), 6.53 (t, J=74Hz, IH), 7.25-7.04 (m, 4H); MS: 402(MH + ). (S)-2-((R)-l-Fluoro-2-morpholin-4-yl-2-oxo-ethyl)-5-ρhenyl -pentanoic acid methyl ester (4c) (Diethylamino) sulfur trifluoride (2.0 ml, 15.2 mmol) was added to a ice cold solution of (R)-2-((S)-l-Hydroxy-2-moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid methyl ester (4a) (0.85 g, 2.5 mmol) in dry methylene chloride (15 ml) and the reaction mixture was stirred overnight while warming to room temperature. The reaction was quenched with aqueous NaHCO 3 solution and extracted with methylene chloride. The organic extracts were dried over Na2SO 4 and concenttated under reduced pressure. Column chromatography on silica eluting with a mixture of ethyl acetate and methylene chloride gave the title compound as an off-white solid (230 mg). *H NMR (CDC1 3 ) δ 1.90- 1.58 (m, 4H), 2.78-2.57 (m, 2H), 3.28-3.10 (m, IH), 3.75 (s, 3H), 3.74-3.45 (m, 8H), 5.40- 5.12 (m, IH), 7.35-7.18 (m, 5H); MS: 338(MH + ). (R)-2-((S)-l-Hydroxy-2-moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid (5a) A solution of (R)-2-((S)-l-hydroxy-2-moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid methyl ester (230 mg, 0.69 mmol) and LiOH.H 2 O (57.5 mg, 1.37 mmol) in a mixture of THF and water (2:1, 6 ml) was stirred at room temperature for 2.5 hrs. The reaction was diluted with water and THF removed under reduced pressure. The pH of the aqueous solution was adjusted to pH5 with IN HCl and extracted with ethyl acetate. The combined organic extracts were dried over MgSO 4 and evaporated under reduced pressure to give the title compound as white solid (180 mg); 1HNMR (CDCI3) δ 1.92-1.60 (m, 4H), 2.75-2.60 (m, 3H), 3.78-3.45 (m, 9H), 4.5 (d, J=8Hz, IH), 7.35-7.18 (m, 5H); MS: 322(MH + ). ( R)-5-(2-Difluoromethoxy-phenyl . -2-((S)- 1 -hvdroxy-2-moφholm -4-yl-2-oxo-ethyl)-pentanoic acid (5b) Similarly prepared according to the procedure above but using (R)-5-(2- difluoromethoxy-phenyl)-2-((S)- 1 -hydroxy-2-moφholin-4-yl-2-oxo-ethyl)-pentanoic acid methyl ester; 1HNMR (CDC1 3 ) δ 1.90-1.65 (m, 4H), 2.77-2.68 (m, 3H), 3.70-3.53 (m, 9H), 4,51 (d, J=4.4Hz, IH), 6.52 (t, J=74Hz, IH), 7.28-7J4 (m, 4H); MS: 388(MH + ). (2R,3S)-2-Benzyl-3-hydroxy-4-morpholm-4-yl-4-oxo-butyric acid (5e) Similarly prepared accordmg to the general procedure above but using (2R, 3S)-2- Benzyl-3-hydroxy-4-moφholin-4-yl-4-oxo-butyric acid methyl ester; 1HNMR (CDC1 3 ) δ 2.90 (m, IH), 3.10 (m, 2H), 3.70-3.15 (m, 8H), 3.75 (m, IH), 4.32 (d J=7.5Hz, IH), 7.38- 7.25 (m, 5H); MS: 294 (MH 1" ). REFERENCE 30 2- Amino- 1 -benzooxazol-2-yl-butan- 1 -one 2-Amino-l-benzooxazol-2-yl-butan-l-one was prepared according to the following reaction protocol: (3a) ri-(Benzooxazol-2-yl-hydroxy-methyl)-propyll-carbamic acid tert-butyl ester (la) DIPEA (0.35 ml, 2 mmol) and di-ttet-butyl dicarbonate (355 mg, 1.63 mmol) were added to a solution of 2-Amino- 1 -benzooxazol-2-yl-butan- 1 -ol (320 mg, 1.55 mmol) in dry methylene chloride (10 ml) and stirred at room temperature for 4 hrs. The reaction was quenched with saturated aqueous NlH jCl and the pH was adjusted to neutral. Oraganic layer separated and the aqueous layer exttacted with methylene chloride. The combined organic extracts were dried over MgSO 4 and concenttated under reduced pressure to give, 1- (Benzooxazol-2-yl-hydroxy-methyl)-propyl]-carbamic acid tert-butyl ester (500 mg). ri-(Benzooxazole-2-carbonyl)-propyll-carbamic acid tert-butyl ester (2a) Dess-Martin Periodinane (15% in DCM, 3.1 mmol) was added to a solution of, 1- (Benzooxazol-2-yl-hydroxy-methyl)-propyl]-carbamic acid tert-butyl ester in dry methylene chloride (15 ml) and stirred at room temperature for 4 hrs. A solution of Na 2 S 2 O 3 in aqueous NaHCO 3 was added and stirred at room temperature. Organic layer was separated and the aqueous was exttacted with methylene chloride. The combined organic extracts were dried over Na 2 SO 4 and concentrated under reduced pressure to give a pale brown solid. Column chromatography on silica eluting with a mixture of methylene chloride and heptane gave the title compound as off white solid (380 mg). 2-Amino- l-benzooxazol-2-yl-butan-l -one hydrochloride (3 a. Hydrogen chloride in dioxane (IM, 1 ml) was added to a solution of, 1- (Benzooxazole-2-carbonyl)-propyl]-carbamic acid tert-butyl ester (2a) in dry methylene chloride (3 ml) and stirred at room temperature for 4 hrs. Concenttation under reduced pressure gave the title compound as white solid (65 mg); J H NMR (CDC1 3 ) δ 0.99 (t, J=7.5Hz, 3H), 2.20-2.05 (m, 2H), 4.96 (m, IH), 7.58 (t, J=7.4Hz, IH), 7.69 (t, J=7.4Hz, IH), 7.94 (d, J=8.2Hz, IH), 8.04 (d, J=8.2Hz, IH), 8.75 (m, 3H); MS: 207(MH + ). (l-Amino-cvclopropyl)-oxazol-2-yl-methanone hydrochloride (3b) 1H NMR (DMSO) δ 1.79 (m, 2H), 1.22 (m, 2H), 7.58 (s, IH), 8.49 (s, IH), 9.22 (m, 3H); MS: 153(MH + ). REFERENCE 31 2-Amino- 1 -oxazol-2-yl-bu tan- 1 -ol 2-Amino- l-oxazol-2-yl-butan-l-ol was prepared according to the following reaction scheme: 2 HCl Step l To a stirring solution of of the BOC-L-α-aminobutyric acid (1, 17.75g, 87.3mmol) in dry methylene chloride (35ml) was added DIEA (33.45ml) followed by the N,O- dimethylhydroxylamine hydrochloride (9.37g, 96.03mmol) and PYBOP (50.0g, 96.03mmol). The reaction mixture was stirred overnight at room temperature. After the solvent was removed in vacuo, the oily residue was dissolved in ether and the precipitate which formed was filtered and the filtrate was concentrated to give 35. Og of a brown oil. The residue was dissolved in ethyl acetate and washed twice with 0.05N HCl, saturated sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate and concenttated to give 14.0g of the product 2, which was used without further purification. Step 2 Compound 2 (8.4g, 34. lmmol) was then dissolved in 30 ml of dry THF and cooled to -50° C under nitrogen, then LAH (1.0 M in THF, 37.5ml, 37.5 lmmol) was added drop wise over 30 minutes. The reaction was stirred for 1.5 hours at -50 ° C then allowed to warn to 0 ° C over 45 minutes. Then NaHSO4 (6.12g, 44.33mmol) was added slowly followed by cold water (2.0ml) and stirring was continued for 30 minutes. The reaction was filtered through celite, which was washed with methylene chloride. The volatiles were removed from the filtrate in vacuo. The solid residue was dissolved in ethyl acetate and washed with cold 0.05N HCl, water and brine. The organic layer was dried over magnesium sulfate, filtered and concenttated to give 6.5 grams of compound 3 as colorless oil. Step 3 Triethylborane (1.0 M in THF, 149.5ml, 149.5mmol) was added to oxazole (10.33g, 149.5mmol) and stirred for 45 minutes at room temperature. The mixture was then cooled to -78 ° C and n-BuLi (2.5 M in hexane, 59.8ml, 149.5mmol) was added dropwise and allowed to stir for one hour under nitrogen. Compound 3 (8.0g, 42.7mmol) was dissolved in 25 ml of THF and added to the reaction mixture. The reaction was stirred for 5 hours at -78 ° C then it was allowed to warm to 0 ° C for one hour. The reaction was then cooled back to A8 ° C and quenched with 7% acetic acid in ethanol (700ml) which was allowed to stir overnight at room temperature. The mixture was concenttated in vacuo and the residue was dissolved in ether and filtered. The filtrate was concentrated in vacuo and the residue was dissolved in ethyl acetate washed twice with 0.005 N HCl, twice with sat'd sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica using 10-40% ethyl acetate/heptane to give 3.85 grams of pure product 4. Step 4 To a solution of compound 4 (1. Ig, 4.29mmol) in dry methylene chloride (10.0ml), stirring under nitrogen at room temperature, was added 4M HCl (in dioxane, 10.73ml) dropwise followed by 5 ml of methanol. The reaction was stirred overnight then concenttated in vacuo to give 1.2 grams of compound 5 as a brown solid. The following reference compounds were prepared according to the protocol described in Reference 31: 2-Amino-3 ,3-dime thyl- 1 -oxazol-2-yl-bu tan- 1 -ol 2-Amino- 1 -oxazol-2-yl-4-phenyl-butan-l -ol LCMS retention time 1.10 minutes; M+l (233.1) REFERENCE 32 2- Amino-2-methyl-pen tan- 1 -ol 2-Amino-2-methyl-pentan-l-ol was prepared according to the following reaction scheme: Step l S-(+)-Phenylglycinol (1, 25g, 182mmol) was dissolved in trifluoroefhanol (250ml) and ethyl pyruvate (23.3g, 200mmol) was added (exothermic) followed by molecular seives (4 angsttoms) and the reaction was refluxed overnight. The reaction was filtered and concenttated to an oil. The oil was purified on a 500 g silica gel column and eluted with 3:1 heptane/ethyl acetate to give 19.94 grams of compound 2. Step 2 Compound 2 (15.0g, 79mmol) was dissolved in THF (400ml) and cooled to -78 ° C, the boron trifluoride etherate (22.4g, 158mmol) was added over a 15 minute period. The reaction was allowed to stir at -78 degree C for 2 hours and propyl magnesium chloride (2.0 M in ether, 79ml, 158mmol) was added over a one hour period and allowed to stir for 4 hours at -78 ° C. The reaction was allowed to warm to room temperature and stir overnight. The mixture was carefully quenched with sat'd NaHSO4 until pH of 8 was obtained. The reaction was exttacted with ethyl acetate (2x200ml), then washed with water, brine, dried over sodium sulfate and concentrated to dryness. The residue was purified on silica eluting with 4: 1 heptane/ethyl acetate to give 12.2 grams of compound 3. Steps 3 and 4 Compound 3 (9.0g, 39mmol) was dissolved in ethanol (100ml) and water (20ml) followed by the addition of 9 grams of Pd(OH)2 and TFA (4ml). The mixture was hydrogenated at 50 psi for 48 hours, then the reaction was filtered through celite which was concentrated to give 9 grams of crude material 4 which was used without further purification. Compound 4 was dissolved in dry methanol (300ml) and HCl gas was bubbled through for 15 minutes. The reaction was stirred at room temperature for three days and was concenttated. The crude product was purified on silica eluting With 1:1 heptane/ethyl acetate to give 3.9 grams of compound 5. Step 5 A mixture of compound 5 (3,9g, 27mmol), (BO 2O (5.88g, 27mmol), and TEA (7.56ml, 54mmol) in 100 ml of dioxane and 100ml of water were stirred overnight at room temperature. The reaction mixture was concentrated and dissolved in ethyl acetate and washed with brine. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified on silica eluting with 30 ethyl acetate/heptane to give 6.68 gram of pure product 6. Step 6 A solution of compound 6 (6.68g, 27mmol) in 200ml of THF was cooled to 0 ° C and LAH (l.OM in THF, 32.4ml, 32.4mmol) was added dropwise and the reaction was stirred for 30 minutes then allowed to come to room temperature. The reaction was stirred for another 30 minutes and the reaction was quenched with a solution of NaHS04, the THF was removed in vacuo and the residue was exttacted with ethyl acetate which was washed with brine and concenttated. The product was purified on silica eluting with n-heptane to 5% methanol/ethyl acetate to give 2.8767 g of compound 7. Step 7 Compound 7 (0.5g) was dissolved in 5 ml of 4N HCL in dioxane and stirred for 1 hour at room temperature. The reaction was concenttated and dried under high vacuum to give 0.3859g of compound 8, which was used without further purification. The following reference compounds were prepared according to the protocol described in Reference 32: 2- Amino-2-me thyl-4-phenyl-butan- 1 -ol 2- Amino-2-methyl-butan- 1 -ol REFERENCE 33 2- Amino-2-methyl- 1 -oxazol-2-yl-ρen tan- 1 -one 2-Amino-2-methyl-l-oxazol-2-yl-pentan-l-one was prepared according to the following reaction scheme: Step l A solution of oxalyl chloride (2.0M in CH2C12, 1.5ml, 3mmol) in 5 ml of methylene chloride was cooled to -78 ° C, then DMSO (0.44ml) was added drop wise to the mixture and allowed to stir for 5 minutes. A solution of compound 7 (Scheme 2, 0.4346g, 2.0mmol) in 10 ml of methylene chloride was added drop wise. The reaction was stirred at -78 degree C for 15 minutes and TEA (1.12ml, 8mmol) was added dropwise and the reaction was stirred for 2 hours at room temperature. The reaction was quenched with water and the product was extracted with ethyl acetate, then organic layer was washed with brine and the solvent was removed in vacuo. The crude product was purified on silica eluting with heptane to 10% ethyl acetate/heptane to give 0.3131 g of pure compound 9. Step 2 Triethylborane (1.0 M in THF, 4.84ml, 4.84mmol) was added to oxazole (0.3355g, 4.84mmol) in 4 ml of THF and stirred for 30 minutes at room temperature. The mixture was then cooled to -78 ° C and n-BuLi (1.6 M in hexane, 3.025ml, 4.84mmol) was added dropwise and allowed to stir for one hour under nitrogen. Compound 9 (0.2615g, 1.2 lmmol) was dissolved in 5 ml of THF and added to the reaction mixture. The reaction was stirred for 5 hours at -78 ° C, then quenched with 5% acetic acid in ethanol (20ml) which was allowed to stir overnight at room temperature and concentrated in vacuo. Ether was added and the solid was filtered and the filtrate was concentrated and the crude product was purified on silica using 0-20% ethyl acetate/heptane to give 0.2528 grams of pure product 10. Step 3 Dess-Martin periodinane (15% in CH2C12, 4.95g, 1.8mmol) was added to a stirring added to a stirring solution of compound 10 (0.2528g, 0.89mmol) in 5 ml of methylene chloride. The reaction was stirred at room temperature for 3 hours, then the reaction was quenched with a solution of sodium thiosulfate in sat'd sodium bicarbonate. The product was exttacted with ethyl acetate and the organic layer was washed with brine, dried over magnesium sulfate and concenttated in vacuo. The residue was purified on silica eluting with 1:1 ethyl acetate/heptane to 5% methanol/ethyl acetate to give 0.2307 g of pure compound 11. Step 4 Compound 11 (0.2123g, 0.75mmol) was dissolved in 5 ml of 4N HCL in dioxane and stirred for 1 hour at room temperature. The reaction was concentrated and dried under high vacuum to give 0.1713g of compound 8, which was used without further purification. The following reference compounds were prepared according to the protocol described in Reference 33: 2-Amino- 1 -benzooxazol-2-yl-2-me thyl-pentan- 1 -one LCMS retention time 2.45 minutes; M+l (233.1). 2-Amino- 1 -benzooxazol-2-yl-2-methyl-4-phenyl-butan- 1 -one LCMS retention time 2.79 minutes; M+l (295.1) 2-Amino- 1 -benzooxazol-2-yl-2-me thyl-butan- 1 -one LCMS retention time 2.29 minutes; M+l (219.1) 2-Amino-2-methyl- 1 -oxazol-2- yl-propan- 1 -one LCMS retention time 1.63 minutes; M+l (155.1) REFERENCE 34 2--_mino-4-phenyl-butyramide 2-Amino-4-phenyl-butyramide was prepared according to the following reaction scheme: Step l Compound 1 (5g, 15.5mmol) was dissolved in dry ether (150ml) and cooled to -20° C, then perfluoroethyl iodide (25g, lOOmmol) was bubbled into the mixture. The solution was then cooled to -50° C and methyl lithium/lithium bromide complex was added over a 30 minute period. The reaction was stirred for 1.5 hours at this temperature and was then quenched with acetone. After stirring for 15 minutes the reaction was diluted with ether (100ml) and poured onto 100ml of water contain KHSO4. The organic layer was separated and washed with water, brine, dried over sodium sulfate and concentrated to dryness. The material was purified on silica eluting with 1:1 ethyl acetate/heptane to give 1.7 grams of compound 2. Step 2 Compound 2 (0.35g) was dissolved in 4 ml of 4N HCL in dioxane and stured for 1 hour at room temperature. The reaction was concenttated and dried under high vacuum to give 0.2807g of compound 3 which was used without further purification; LCMS retention time 4.19 minutes; M+l (282.1). EXAMPLE 1 N-r(S)-l-(l-Benzooxazol-2-yl-methanoyl)-butyll-3-benzylsulfonyl-2- benzylsulfonylmethyl-propionamide (Compound 1) A mixture comprised of 3-benzylsulfanyl-2-benzylsulfanylmethyl-propionic acid (0.239g, 0.719 mmol), prepared as in Reference 1, in methylene chloride (6 mL), HOBt hydrate (O.Hg, 0.719 mmol), EDC (0.18g, 0.939 mmol), hydroxy amine (0.19 g, 0.86 mmol) and 4-methylmoφholine (0.075 mL) was stirred at room temperature for 1 hour and then poured into cold IN aqueous hydrochloric. The product was exttacted with ethyl acetate and the exttacts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure and the residue was chromatographed on silica gel eluting with ethyl acetate/hexane to give N-[(S)-l-(l-Benzooxazol-2-yl-l-hydroxy-methyl)-butyl]-3- benzylsulfanyl-2-benzylsulfanylmethyl-propionamide (0.217 g). A solution of N-[(S)-l-(l-Benzooxazol-2-yl-l-hydroxy-methyl)-butyl]-3- benzylsulfanyl-2-benzylsulfanylmethyl-propionamide (0.317 g, 0.594 mmol) in methanol (30 mL) was tteated with a solution of Oxone ® (0.913 g, 1.48 mmol) in water (20 mL) and then stirred at room temperature for 7 hours. The methanol was removed by evaporation at reduced pressure and the resulting suspension was diluted with water and the product exttacted with ethyl acetate. The exttacts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure and the residue was chromatographed on silica gel eluting with ethyl acetate/hexane to giveN-[(S)-l-(l-Benzooxazol-2-yl-l-hydroxy-methyl)-butyl]- 3-benzylsulfonyl-2-benzylsulfonylmethyl-propionamide (0.143 g, 41% yield). A solution of N-[(S)-l-(l-Benzooxazol-2-yl-l-hydroxy-methyl)-butyl]-3- benzylsulfonyl-2-benzylsulfonylmethyl-propionamide (0.140 g, 0.234 mmol) in methylene chloride (5 mL) was treated with l,l,l,l-triacetoxy-l,l-dihydro-l,2-benziodoxol-3(lH)- one (Dess-Martin periodinane) (0.127 g, 0.30 mmoL) and the resulting solution was stirred at room temperature for 30 minutes. Aqueous sodium thiosulfate and sodium bicarbonate (15 mL, 0.25 M) were added and the reaction mixture was stirred for 20 minutes. The product was exttacted with ethyl acetate. The exttacts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure and the residue was crystallized from t-butylmethyl ether to give N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-butyl]-3-ber_zylsulfonyl-2-benzyl- sulfonylmethyl-propionamide (0.103 g, 74%); ΝMR (DMSO): 9.15 (d, J=6Hz, IH); 8.01 (d, J=7Hz, IH); 7.89 (d, J=8Hz, IH); 7.65 (t, J=7Hz, IH); 7.54 (t, J=8Hz, IH); 7.37 (m, 10H); 5.36 (m, IH); 4.5 (m, 4H); 3.68 (m, IH); 3.45-3.25 (m, 4H); 1.95 (m, IH); 1.73 (m, IH); 1.47 (m, 2H); 0.91 (t, J=7Hz, 3H); MS: M(H+) 597.0 (596.17); The following compounds were prepared by the method of Example 1 by substituting the required carboxylic acid in place of 3-benzylsulfanyl-2- benzylsulfanylmethyl-propionic acid: N-r(S)-l-(l-Benzooxazol-2-yl-methanoyl)-bu-yll-3-(2-trifluoromethyl- benzylsulfonyl)-2-(2-trifluoromethyl-benzylsulfonylme yl)-propionamide (Compound 2); 1H-ΝMR (CDC1 3 ) δ: 7.93 (m, IH); 7.69 (m, 4H); 7.4-7.6 (m, 6H); 7.20 (m, 2H); 5.58 (m, IH); 4.54 (m, 4H); 3.69 (m, IH); 3.30-3.55 (m, 4H); 1.55-1.90 (m, IH); 1.45 (m, IH); 1.32 (m, 2H); 0.90 (m, 3H); MS: M(+) 733.0; M(-) 731.6; N-r(S)-l-(l-Benzooxazol-2-yl-methanoyl)-pentyll-4-(2-methoxy-benzenesulfonyl)- 2-r2-(2-memoxy-benzenesulfonylVe1_ιyl1-butyramide (Compound 3); -ΝMR (DMSO) δ: 8.65 (d, IH); 7.99 (d, J=7Hz, IH); 7.89 (d, J=8Hz, IH); 7.8-7.5 (m, 6H); 7.3-7.1 (m, 4H) 5.25 (m, IH); 3.90 ( , 9H); 3.3 (m, 6H); 1.6 (m, 4H); 1.3 (m, 2H); 0.85 (m, 3H); MS (M+) 670.2, 670.19; 4-Benzenesulfonyl-2- ( 2-benzenesulfonyl-e thvD-N-IYS)- 1 -( 1 -benzooxazol-2-γl- methanovD-butyll-butyramide (Compound 4); 1H-ΝMR (DMSO) δ: 8.61 (d, I=6Hz, IH); 7.99 (d, J=8Hz, IH); 7.91 (d, J=8Hz, IH); 7.82 (m, 4H); 7.74 (m, 2H); 7.64 (m, 5H); 7.55 (t, J=8Hz, IH); 5.21 (m, IH); 3.3-3.0 (m, 5H); 1.8 (m, IH); 1.6 (m, 5H); 1.3 (m, 2H); 0.86 (t, J=7Hz, 3H); MS: (M+) 597.2, 596.17; (R)-N-[(S)-l-(l-Benzooxazol-2-yl-metlιanoyl)-butyll-2-cvclohexylmethyl-3- benzylsulfonyl-propionamide (Compound 5) ; H ΝMR (DMSO): 8.96 (d, J =6Hz, IH), 8.73 (d, J=6Hz, IH), 7.99 (d, I=8H, IH), 7.87 (m, IH), 7.64 (m, IH), 7.54 (m, IH), 7.37 (m, 5H), 5.29 (m, IH), 4.44 (s, 2H), 4.36 (s, 2H), 3.3-2.8 (m, 2H), 0.6-2.0 (m, 20H); MS: MH 1" 525.4 (524.23); and N-r(S)-l-(l-Benzothiazol-2-yl-methanoyl)-propyll-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide (Compound 6); ^ΝMR: (DMSO), 8.79 (d, J=6.2Hz), 8.72 (d, J=6.2Hz), IH], 8.30-8.22 (m, 2H), 7.71-7.61 (m, 2H), 7.43-7.33 (m, 5H), 5.46- 5.33 (m, IH), 4.53-4.38 (m, 2H), 3.57-3.30 (m, 10H), 3.13-3.02 (m, IH), 2.66-2.54 (m, 2H), 2.04-1.90 (m, IH), 1.83-1.68 (m, IH), 0.97 (t, J=7.2Hz, 3H); MS: (MAI) 558. The method of Example 1 can also be modified by omitting the Oxone ® oxidation step to prepare the following compounds: N-[YS)-1-(1 -Benzooxazol-2-yl-methanoyl)-butyl 1 -3-cvclohexyl-2- cvclohexylmethyl-propionamide (Compound 7); 1H ΝMR (DMSO): 8.50 (d, J=6Hz, IH); 8.00 (d, J=8Hz, IH); 7.89 (d, J=8Hz, IH); 7.62 (t, J=7Hz, IH); 7.53 (t, J=7Hz, IH); 5.2(m, IH); 2.0-0.8 (m, 35H); MS: M(H+) 453.2 (452.3); N- F(S ) - 1 -( 1 -Benzooxazol-2-yl-methanoyl)-butyl] -3-isobutylsulf anyl-2- isobutylsulfanylmethyl-propionamide (Compound 8); J H ΝMR (DMSO): 8.73 (d, J =5Hz, IH); 7.76 (d, J=7Hz, IH); 7.87 (d, J=8Hz, IH); 7.62 (dt, J =7,lHz, IH); 7.52 (dt, J=8,lHz, IH); 5.26 (m, IH); 2.7 (m, IH); 2.55 (m, 4H); 2.34 (d, J=7Hz, 2H); 2.29 (d, J=7Hz, 2H); 1.9 (m, IH); 1.66 (m, 3H); 1.45 (m, 2H); 0.91 (t, J=6Hz, 3H), 0.90 (d, J=6Hz, 6H), 0.88 (d, J=3Hz, 3H), 0.84 (d, J=3Hz, 3H); MS: M(H+) 465.0 (464.22); N-r(S)-l-(l-Benzooxazol-2-yl-methanoyl)-butyl1-3-benzylsulfanyl-2- benzylsulfanylmethyl-propionamide (Compound 9); 1H ΝMR (DMSO): 8.80 (d, J=7Hz, IH); 7.98 (d, I=8Hz, IH); 7.88 (d, I=8Hz, IH); 7.63 (t, J=7Hz, IH); 7.53 (t, J=7Hz, IH); 7.3-7.2 (m, 10H); 5.32 (m, IH); 3.71 (s, 2H); 3.65 (d, J=3Hz, 2H); 2.87 (m, IH); 2.45-2.3 (m, 4H); 2.0-1.4 (m, 4H); 0.92 (t, J=7Hz, 3H); MS: M(H+) 533.0 (532.19); and N-r(S)-l-(l-Benzooxazol-2-yl-methanoyl)-butvn-4-phenylsulfanyl-2-(2- phenylsulfanyl-ethvD-butyramide (Compound 10); 1H ΝMR (DMSO): 8.73 (d, J=6Hz, IH); 7.99 (d, J=8Hz, IH); 7.88 (d, J=8Hz, IH); 7.65 (t, J=8Hz, IH); 7.53 (t, J=8Hz, IH); 7.35-7.1 (m, 10H); 5.3 (m, IH); 2.85 (m, 4H); 2.65 (m, IH); 2.0-1.3 (m, 8H); 0.91 (t, J=7Hz, 3H); MS: M(H+) 533.0 (532.19). EXAMPLE 2 N-Cyanomethyl-4-morpholin-4-yl-4-oxo-2-(2-trifluoromethyl-benzyl-sulfonylmethyl)- butyramide (Compound 11) A mixture comprised of 4-moφholin-4-yl-4-oxo-2-(2-trifluoromethyl- benzylsulfonylmethyl)-butyric acid (200mg, 0.47mmol), prepared as in reference 5, EDC (200mg, 1.05mmol), HOBt (200mg, 1.3mmol), and aminoacetonitrile hydrochloride (150mg, 1.6mmol) was tteated with dichloromethyl (4mL) and 4-methylmoφholine (0.5mL). The mixture was stirred at ambient temperature for 2 hours. After dilution with ethyl acetate (150mL), the solution was washed with water (30mL), saturated aqueous ΝaHCO 3 solution and brine, dried with magnesium sulfate and evaporated under vacuum. The product was crystallized from ethyl acetate/hexane to yield N-cyanomethyl-4- moφholin-4-yl-4-oxo-2-(2-trifluoromemyl-benzyl-sulfonylmethyl)-butyramide (156mg) as a yellowish solid; Η ΝMR: (DMSO) 8.87 (t, J=5.5Hz, IH), 7.81-7.57 (m, 4H), 4.74 (d, J=14.5Hz, IH), 4.67 (d, J=14.5Hz, IH), 4.13 (d, J=5.5Hz, 2H), 3.63-3.26 (m, IIH), 2.75 (dd, J=6.4Hz, J=16.8Hz, IH), 2.65 (dd, J=6.2Hz, J=16.8Hz, IH); MS: (M + +l) 462; The following compounds of Formula I were provided by proceeding as in Example 2: N 4 -(4-Carbamoyl-phenyl)-N 1 -cvanomethyl-2-benzyl-sulfonylmethyl-succinamide (Compound 19); J H ΝMR: (DMSO) 10.24 (s, IH), 8.93 (t, J=5.5Hz, IH), 7.83 (s, IH), 7.81 (d, J=8.4Hz, 2H), 7.60 (d, J=8.4Hz, 2H), 7.44-7.35 (m, 5H), 7.23 (s, IH), 4.53 (d, J=13.6Hz, IH), 4.48 (d, J=13.6Hz, IH), 4.14 (m, 2H), 3.50-3.30 (m, 2H), 3.20 (dd, J=4.7Hz, J=13.1Hz, IH), 2.73 (d, J=6.7Hz, 2H); MS: (M + +l) 443; and N-Cvanomethyl-2-r2-(l,l-difluoro-memoxy)-benzylsulfonylmethyl1-4-morpholin- 4-yl-4-oxo-butyramide (Compound 25); 1H ΝMR: (DMSO) 8.85 (t, J=5.5Hz, 1H>, 7.52- 7.43 (m, 2H), 7.31-7.22 (m, 2H), 7.13 (t, J H>F =74Hz, IH), 4.53 (s, 2H), 4.11 (d, J=5.5Hz, 2H), 3.58-3.20 (m, IIH), 2.72 (dd, J=6.7Hz, J=16.8Hz, IH), 2.63 (dd, J=5.9Hz, J=16.8Hz, IH); MS: (M + +l) 460; EXAMPLE 3 N-r(S)-l-(l-Benzooxazol-2-yl-methanoyl)-propyn-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide (Compound 29) A mixture comprised of 4-Moφholin-4-yl-4-oxo-2-(benzyl-sulfonylmemyl)-butyric acid (300mg, 0.84mmol), EDC (250mg, 1.3mmol), HOBt (250mg, 1.6mmol) and (2S)-2- amino-l-benzooxazol-2-yl-butan-l-ol (250mg, 1.2mmol) was treated with dichloromethyl (4mL) followed by 4-methylmoφholine (0.5mL). The mixture was stirred at ambient temperature for 2 hours. After dilution with ethyl acetate (150mL), the solution was washed with IN aqueous HCl, water, saturated aqueous ΝaHCO 3 solution and brine, dried with magnesium sulfate and evaporated under vacuum. The crude product was dissolved in dry dichloromethyl (lOmL) and l,l,l,l-triacetoxy-l,l-dihydro-l,2-benziodoxol-3(lH)- one (Dess-Martin periodinane) (500mg, 1.2mmol) was added. After stirring at ambient temperature for 1 hour, the mixture was diluted with ethyl acetate (150mL) and treated with 0.26M Na 2 S 2 O 3 solution in saturated aqueous NaHCO 3 . The organic phase was washed with saturated aqueous NaHCO3 and brine, dried with magnesium sulfate and evaporated to yield N-r(S)-l-(l-Benzooxazol-2-yl-methanoyl)-propyl]-4-morpholin-4-yl-4- oxo-2-benzylsulfonylme yl-butyramide (377mg) as mixture of diastereomers. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate ratio of 1:2 to 1:4); 1H ΝMR: (DMSO), 8.85 (d, J=6.2Hz), 8.77 (d, J=6.2Hz), 1H]„ 8.00 (d, J=7.7Hz), 7.99 (d, J=7.7Hz), 1H]„ 7.90 (d, J=8.2Hz), 7.89 (d, J=8.2Hz), IH], 7.64 (t, J=7.9Hz, IH), 7.54 (t, J=7.4Hz, IH), 7.42-7.34 (m, 5H), 5.25-5.12 (m, IH), 4.55-4.38 (m, 2H), 3.60-3.28 (m, 10H), 3.12-3.02 (m, IH), 2.64-2.50 (m, 2H), 2.08-1.91 (m, IH), 1.82-1.65 (m, IH), 0.98 (t, J=7.4Hz, 3H); MS: (M + +l) 542; The following compounds of Formula I were provided by proceeding as in Example 3: N- 1 " ( S ) - 1 -( 1 -Benzooxazol-2-yl-methanoyl)-pen tyl] -4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide (Compound 30); ΗΝMR: (DMSO), 8.84 (d, J=6.4Hz), 8.76 (d, J=6.4Hz), 1H]„ 8.00 (d, J=7.7Hz), 7.98 (d, J=7.7Hz), 1H]„ 7.89 (d, J=8.2Hz), 7.88 (d, J=8.2Hz), IH], 7.64 (t, J=7.9Hz, IH), 7.53 (t, J=7.4Hz, IH), 7.42-7.34 (m, 5H), 5.30- 5.17 (m, IH), 4.53-4.37 (m, 2H), 3.56-3.26 (m, 10H), 3.12-3.00 (m, IH), 2.66-2.52 (m, 2H), 2.00-1.86 (m, IH), 1.76-1.61 (m, IH), 1.48-1.22 (m, 4H), 0.85 (t, J=6.9Hz, 3H); MS: (M + +l) 570; (S)-2,2-Difluoro-4-(4-morpholm-4-yl-4-oxo-2-benzylsulfonylmethyl- butanoylamino)-3-oxo-hexanoic acid dimethylamide (Compound 31); 1HΝMR: (DMSO) 8.63-8.57 (m, IH), 7.43-7.34 (m, 5H), 4.69-4.57 (m, IH), 4.55-4.41 (m, 2H), 3.59-3.30 (m, 10H), 3.14-3.04 (m, 1H)„ 2.98 (s), 2.96 (s), 3H]„ 2.90 (s), 2.88 (s), 3H], 2.70-2.58 (m, 2H), 1.90-1.72 (m, IH), 1.66-1.50 (m, IH), 0.89 (t, J=6.9Hz, 3H); MS: (M + +l) 546; and N-r(S)-l-(l-Benzylcarbamoyl-methanoyl)-propyl1-4-morpholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide (Compound 32); ΗΝMR: (DMSO) 9.26-9.19 (m, 1H)„ 8.56 (d, J=6.7Hz), 8.51 (d, J=6.9Hz), IH], 7.44-7.19 (m, 10H), 4.96-4.85 (m, IH), 4.53- 4.40 (m, 2H), 4.38-4.22 (m, 2H), 3.57-3.30 (m, 10H), 3.11-2.99 (m, IH), 2.65-2.52 (m, 2H), 1.86-1.71 (m, IH), 1.61-1.48 (m, IH), 0.89 (t, J=7.2Hz, 3H); MS: (M + +l) 558. EXAMPLE 5 3-Biphenyl-3-yl-N-cvanomethyl-2-benzylsulfonylmethyl-propionamide (Compound 35) 3-Biphenyl-3-yl-2-benzylsulfonylmethyl-propionic acid (300mg, 0.76mmol), prepared as in Reference 9, was combined with EDC (300mg, 1.57mmol), HOBt (300mg, 1.96mmol), and aminoacetonitrile hydrochloride (150mg, 1.6mmol). Dichloromethyl (4mL) was added and then 4-methylmoφholine (0.5mL). The mixture was stirred at ambient temperature for 2 hours. After dilution with ethyl acetate (150mL), the solution was washed with water (30mL), saturated aqueous ΝaHCO 3 solution and brine, dried with magnesium sulfate and evaporated under vacuum. The product, 3-biphenyl-3-yl-N- cyanomethyl-2-benzylsulfonylmethyl-propionamide (273mg), was crystallized from ethyl acetate/hexane as a white solid; 1HΝMR: (DMSO) 8.87 (t, J=5.5Hz, IH), 7.68-7.14 (m, 14H), 4.45 (d, J=13.8Hz, IH), 4.38 (d, J=13.8Hz, IH), 4.13 (m, 2H), 3.49 (dd, J=9.4Hz, J=14.1Hz, IH), 3.28-3.11 (m, IH), 3.04-2.76 (m, 3H). MS: (M + +l) 433. Proceeding as in Example 5 provided the following compound of Formula I: 3-Biphenyl-4-yl-N-cvanomethyl-2-benzylsulfonylmemyl-propion-m_ide (Compound 36); J H ΝMR: (DMSO) 8.86 (t, J=5.5Hz, IH), 7.65 (d, J=7.4Hz, 2H), 7.59 (d, J=7.4Hz, 2H), 7.47 (t, J=7.7Hz, 2H), 7.39-7.24 (m, 8H), 4.47 (d, J=13.8Hz, IH), 4.40 (d, J=13.8Hz, IH), 4.13 (m, 2H), 3.48 (dd, J=9.4Hz, J=14.1Hz, IH), 3.23-3.11 (m, IH), 3.04-2.75 (m, 3H). MS: (M + +l) 433; and 3-(3-Bromo-phenyl)-N-cyanomethyl-2-benzylsulfonylmethyl-propionarnide (Compound 37); J H ΝMR: (DMSO) 8.84 (t, J=5.5Hz, IH), 7.46-7.14 (m, 9H), 4.46 (d, J=13.8Hz, IH), 4.40 (d, J=13.8Hz, IH), 4.10 (m, 2H), 3.46 (dd, J=9.4Hz, J=14.1Hz, IH), 3.18-3.07 (m, IH), 2.97 (dd, J=14.1Hz, J=3.4Hz, IH) 2.88-2.73 (m, 2H). MS: (M + +l) 435/437. EXAMPLE 6 N-r(S)-l-((E)-2-Benzenesulfonyl-vinyl)-pentyl1-3-benzylsulfonyl-2- benzylsulfonylmethyl-propionamide (Compound 38) A mixture of 3-benzylsulfanyl-2-benzylsulfanylmethyl-propionic acid (161 mg), prepared as in Reference 1, 3-benzenesulfonyl-l-n-butylallylamine tosylate (212 mg), HOBt monohydrate (77 mg) and EDC (125 mg) in methylene chloride (6 mL) was tteated with Ν-methylmoφholine (0.25 mL) and stirred at room temperature for 2.5 hours. The reaction mixture was poured into ice cold dilute hydrochloric acid. The product was exttacted with ethyl acetate and the organic exttacts were washed with aqueous sodium bicarbonate and then with saturated sodium chloride. After drying over magnesium sulfate the solvents were evaporated to give a residue which was crystallized from ethyl acetate/t- butylmethyl ether to yield N-[(S)-l-((E)-2-benzenesulfonyl-vinyl)-pentyl]-3- benzylsulfanyl-2-benzylsulfanylmethyl-propionamide (160 mg). A solution of N-[(S)-l-((E)-2-benzenesulfonyl-vinyl)-pentyl]-3-benzylsulfanyl-2- benzylsulfanylmethyl-propionamide (50 mg) in methylene chloride (5 mL) was treated with m-chloroperbenzoic acid (108 mg) and then stirred at room temperature for 65 minutes. The reaction mixture was stirred with aqueous sodium bisulfite and sodium bicarbonate for 85 minutes and then exttacted with methylene chloride. The organic exttacts were washed with saturated aqueous sodium chloride and dried over magnesium sulfate. Evaporation of the solvent gave a residue which was precipitated from ethyl acetate/t-butylmethyl ether to give N-r(S)-l-((E)-2-benzenesulfonyl-vmyl)-pentyri-3- benzylsulfonyl-2-benzylsulfonylmefhyl-propionamide (37 mg); 1H ΝMR (DMSO): 8.61 (d, J=8Hz, IH), 7.80 (d, J=7Hz, 2H), 7.69 (t, J=7H, IH), 7.58 (t, J=8Hz, 2H), 7.38 (m, 10H), 6.86 (m, 2H), 4.6-4.3 (m, 5H), 3.5-3.4 (m, 5H), 1.5 (m, 2H), 1.2 (m, 4H), 0.8 (m, 3H); MS: MH + 632.2 (631.17). Proceeding as in Example 6 provided the following compound of Formula I: Ν-(3-Benzenesulfonyl-l-phenethyl-allyl)-3-benzylsulfonyl-2-benzylsulfonylmethyl- propionamide (Compound 39); 1H NMR (DMSO): 8.75 (d, J=8Hz, IH), 7.80 (d, J=7Hz, 2H), 7.70 (t, J=7H, IH), 7.58 (t, J=8Hz, 2H), 7.4-7.1 (m, 15H), 6.9 (m, 2H), 4.6-4.2 (m, 5H), 3.6-3.3 (m, 5H), 2.6 (m, 2H), 1.8 (m, 2H); MS: MH + 680.4 (679.17); EXAMPLE 7 N-Cyanomethyl-3-(3-eyano-benzylsulfonyl)-2-benzylsulfonyl-methyl- propionamide (Compound 40) A mixture of 3-acetylsulfanyl-2-benzylsulfanylmethyl-propionic acid (0.200g), prepared as in Reference 10, HOBt hydrate (0.13g), aminoacetonitrile hydrochloride (0.15g) and EDC (0.26g) was tteated with methylene chloride (6 mL) and Ν- methylmoφholine (0.35 mL). After stirring for 80 minutes at room temperature, the reaction mixture was diluted with ethyl acetate (50mL) and washed sequentially with water, aqueous sodium bicarbonate and saturated aqueous sodium chloride. The solution was dried over magnesium sulfate and evaporated to give thioacetic acid S-[3- benzylsulfanyl-2-(cyanomethyl-carbamoyl)-propyl] ester (0.218 g). A solution of thioacetic acid S-[3-benzyIsulfanyl-2-(cyanomethyl-carbamoyI)- propyl] ester (0.105 g) in dimethylformamide (1 mL) and water (0.8 mL) was cooled on ice and tteated with 1 N aqueous potassium hydroxide (0.65 mL). 3-Cyanobenzylbromide (0.129 g) in dimethylformamide (0.8 mL) was added. The reaction mixture was allowed to warm to room temperature while stirring overnight. The reaction mixture was then poured into ice water and exttacted with ethyl acetate (50 mL) and washed with water and saturated aqueous sodium chloride. The solution was dried over magnesium sulfate and evaporated to give 2-benzylsulfanylmethyl-3-(3-cyano-benzylsulfanyl)-N-cyanomethyl- propionamide (0.135 g). 2-Benzylsulfanylmethyl-3-(3-cyano-benzylsulfanyl)-N-cyanomemyl-propionamide (0.135 mg) in methanol (lOmL) was tteated with a solution of Oxone ® (0.615g) in water (1.3mL) and the resulting mixture was stirred at room temperature for 45 minutes. The reaction mixture was diluted with water (50mL) and then the methanol was removed by rotary evaporation. The residue was diluted with ethyl acetate and water. The product was extracted with ethyl acetate and the organic layer washed with water and saturated aqueous sodium chloride. The solution was dried over magnesium sulfate and evaporated to give N-Cvanomethyl-3-(3-cvano-beι_zylsulfonyl)-2-benzylsulfonylmemyl-propionamide(0J38 g); J H ΝMR: (DMSO) 9.19 (t, J=5Hz, IH), 7.88 (d, J=8Hz, IH), 7.82 (s, IH), 7.72 (d, J=9Hz, IH), 7.62 (t, J=8Hz, IH), 7.38 (s, 5H), 4.65 (d, J=14Hz, IH), 4.58 (d, J=14Hz, IH), 4.53 (d, J=13Hz, IH), 4.47 (d, J=13Hz, IH), 4.17 (d, J=5Hz, 2H), 3.5-3.3 (m, 5H); MS: (M + +l) 460.2; 459.09. EXAMPLE 8 4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-{(S)-l-ri-(3-phenyl- ri,2,4]oxadiazol-5-yl)-methanoyll-ρropyl}-butyramide (Compound 41) A mixture of (S)-2-amino-l-(3-phenyl-[l,2,4]oxadiazol-5-yl)-butan-l-one, prepared as in Reference 11, 4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (200mg, 0.56mmol), EDC (200mg, 1.05mmol), HOBt (200mg, 1.30mmol), CH 2 C1 2 (4mL) and 4- methylmoφholine (0.5mL) was stirced at ambient temperature for 2 hours. After dilution with ethyl acetate (150mL), the solution was washed with water (30mL), saturated aqueous NaHCO 3 solution and brine, dried with MgSO and evaporated under vacuum. The crude product was dissolved in dry dichloromethyl (lOmL) and 1,1, 1,1 -ttiacetoxy- 1,1 -dihydro- l,2-benziodoxol-3(lH)-one (Dess-Martin periodinane) (500mg, 1.2mmol) was added. After stirring at ambient temperatures for 1 hour, the mixture was diluted with ethyl acetate (150mL) and treated with Na 2 S 2 O 3 solution (0.26M) in saturated aqueous NaHCO 3 . The organic phase was washed with saturated aqueous NaHCO 3 and brine, dried with MgSO and evaporated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate in a 1:2 to 1:4 ratio) to yield 4-Moφholin-4-yl-4-oxo-2- benzylsulf onylmethyl-N- 1 ( S ) - 1 - f 1 -(3-phenyl- r 1 ,2,41 oxadiazol-5-yl)-methanovn -propyl j - butyramide (150mg) as mixture of diastereomers; *H ΝMR: (DMSO), 9.03 (d, J=5.9Hz), 8.89 (d, J=6.4Hz), IH], 8.09-8.03 (m, 2H), 7.66-7.55 (m, 3H), 7.42-7.33 (m, 5H), 4.97- 4.78 (m, IH), 4.53-4.35 (m, 2H), 3.58-3.02 (m, IIH), 2.65-2.50 (m, 2H), 2.06-1.90 (m, IH), 1.83-1.66 (m, IH), 0.97 (t, J=7.2Hz, 3H); MS: (M + +l) 569. Example 9 N-Cyanomethyl-2- \2- 1.1 -difluoro-mefhoxy)-benzylsulf anylmethvH -3- benzylsulfanyl-propionamide (Compound 42): Anιixtureof2-benzylsulfanylmethyl-3-[2-(l,l-difluoromethoxy)-benzyl-sulfanyl]- propionic acid (96 mg, 0.241 mmol)(prepared above in Reference 2), HOBt hydrate (37 mg, 0.24 mmol), aminoacetonitrile hydrochloride (33 mg, 0.36 mmol), EDC (69 mg, 0.36 mmol) and N-methylpyrolidinone (1 mL) was tteated with N-methylmoφholine (0.050 mL) and then stirced at room temperature for 3 hours. The reaction mixture was then poured into cold dilute HCl and the product exttacted with ethyl acetate, The organic exttacts were washed with aqueous sodium bicarbonate then saturated sodium chloride and dried over magnesium sulfate. Evaporation of the solvent then gave N-cyanomethyl-2-r2- lJ-difluoro-methoxy)-benzylsulfanylmethyl1-3-benzylsulfanyl-propionamide (46 mg). The following compounds of Formula 1 are provided by this method by substitution of 2-benzylsulfanylmethyl-3-[2-(l,l-difluoromethoxy)-benzylsulfanyl]-propionic acid with the appropriate carboxylic acid: N-Cyanomethyl-3-( " 2-trifluoromethyl-benzylsulfanyl)-2-(2-trifluoro- methyl-benzylsulfanylmethvD-propionamide (Compound 43); 'H-ΝIVIR (CDC1 3 ) δ: 7.57 (m, 6H); 7.36 (t, J=7.4 Hz, 2H); 6.01 (m, IH); 4.16 (d, J=5.9 Hz, 2H); 3.86 (s, 4H); 2.70 (m, 4H); 3.35 (m, IH); MS: (M+) 507.0, M(-) 504.2; N-Cvanomethyl-3-isobutylsulfanvI-2-isobutylsulfanylmethyl-propionamide (Compound 44); 1H ΝMR (DMSO): 8.77 (t, J=6 Hz, IH), 4.5 (d, J=6 Hz, 2H), 2.60 (s, 5H), 2.34 (d, J=7 Hz, 4H), 1.70 (hept, J=7 Hz, 2H), 0.91 (d, J=7Hz, 12H); MS: M(H+) 303.0 (302.15); N-Cvanomethyl-4-phenylsulfanyl-2-(2-phenylsulfanyl-ethylVbutyramide (Compound 45); 1HΝMR (DMSO): 8.83 (t, J=5Hz, IH); 7.3 (m, 10H); 4.22 (d, J=6Hz, 2H); 2.90 (m, 4H); 2.65 (m, IH); 1.85 (m, 2H); 1.72 (m, 2H); MS: M(H+) 370.4 (370.12); N-Cyanomethyl-3- 2-( 1 , 1 -difluoro-methoxy)-benzylsulfanyl] -2-r2-( 1 , 1 -difluoro- methoxy)-benzylsulfanylmethyl1-proρionamide (Compound 46); 1H ΝMR (DMSO): 8.88 (t, J=5Hz, IH); 7.4-7.1 (m, 8H); 7.15 (t, J=74Hz, 2H); 4.18 (t,J=3Hz, 2H); 3.74 (d, J=13Hz, 4H); 2.75 (m, IH); 2.65-2.5 (m, 4H); MS: M(H+) 504.1 (502.1); and 3-Benzylsulfanyl-2-benzylsulfanylmethyl-N-cvanomethyl-propionamide (Compound 47); J H ΝMR (DMSO): 8.86 (t, J=6Hz, IH); 7.26 (m, 10H); 4.20 (d, J=5Hz, 2H); 3.7 (s, 4H); 2.73 (m, IH); 2.55-2.37 (m, 4H); MS: M(H+) 370.4 (370.12). Example 10 Ν-Cvanomethyl-2-r2-l,l-difluoro-methoxy)-benzylsulfonylmethvn-3- benzylsulfonyl-propionamide (Compound 48) A solution of N-cyanomethyl-2-[2-(l , l-difluoro-methoxy)-benzyl-sulfanylmethyl]- 3-benzylsulfanyl-propionamide (46 mg) in methanol (5 mL) was treated with Oxone ® (184 mg in 2.5 mL of water) and stirred at ambient temperature for 18 hours. An additional portion of Oxone ® (166mg in 1.5 mL of water) was added along with more methanol (10 mL) and the reaction mixture was stirred again for 18 hours. Water was added to the reaction mixture and the methanol was removed by rotary evaporation and the product was exttacted with ethyl acetate. The organic extracts were washed with aqueous sodium bicarbonate then saturated sodium chloride and dried over magnesium sulfate. Evaporation of the solvent then gave N-cvanomethyl-2-r2-(l,l-difluoro-methoxy)- benzylsulfonylmethyll-3-phenyl-methylsulfonyl-propionamide (67 mg); H NMR (DMSO): 9.19 (t, J =5 Hz, IH), 7.47 (m, 2H), 7.38 (s, 5H), 7.25 (m, 2H), 7.13 (t, J=74Hz, IH), 4.54 (s, 2H), 4.53 (d, J=14 Hz, IH), 4.46 (d, J = 14 Hz, IH), 4.16 (d, J = 5 Hz, 2H), 3.5 (m, 5H); MS: M(H+) 501.0 (500.09). The following compounds of Formula 1 are provided by this method by substitution ofN-cyanomethyl-2-[2-(l,l-difluoro-methoxy)-benzyl-sulfanylmethyl]-3-benzylsulfanyl- propionamide with the appropriate N-cyanomethyl propionamide: N-Cvanomethyl-3-(2-trifluoromethyl-benzylsulfonyl)-2-(2-trifluoromethyl- benzylsulf onylmethvD-propionamide. (Compound 49); Η-ΝMR (DMSO) δ: 9.23 (t, J=5.4 Hz, IH); 7.79 (m, 2H); 7.67 (m, 6H); 4.72 (m, 4H); 4.18 (t, J=2.7 Hz, 2H); 3.53-3.76 (m, 5H); MS: M(+) 539.0; M(-) 536.6; 4-Benzenesulfonyl-2-(2-benzenesulfonyl-ethyl)-N-cvanomethyl-butyramide (Compound 50); 1HΝMR (DMSO): 8.67 (t, J=5Hz, IH); 7.85 (m, 4H); 7.73 (m, 2H); 7.64 (m, 4H); 4.06 (m, 2H); 3.12 (m, 4H); 2.4 (m, IH); 1.66 (m, 4H); MS: M(H+) 435.2 (434.10); N-Cvanomethyl-3-r2-(l,l-difluoro-methoxy)-benzylsulfonyl]-2-r2-(l,l-difluoro- methoxy)-benzylsulfonylmethvn-propionamide (Compound 51); HΝMR (DMSO): 9.17 (t, J=5Hz, IH); 7.5-7.4 (m, 4H); 7.3-7.2 (m, 4H); 7.12 (t, J=74Hz, 2H); 4.54 (s, 4H); 4.15 (m, 2H); 3.6-3.4 (m, 5H); MS: M(H+) 567.2 (566.08); and N-Cvanomethyl-3-benzylsulfonyl-2-benzylsulfonylmethyl-propionamide (Compound 52); 1H ΝMR (DMSO): 9.19 (t, J=5Hz, IH); 7.38 (s, 10H); 4.53 (d, J=14Hz, 2H); 4.46 (d,J=14Hz, 2H); 4.17 (t, J=3Hz, 2H); 3.5-3.3 (m, 5H); MS: M(H+) 435.2 (434.1). The following compounds of Formula I are provided by the methods described in this application: N-r(S)-l-(l-Benzylcarbamoyl-methanoylVproρyl]-3-benzylsulfonyl-2- benzylsulfonylmethyl-proρionamide(Compound 53); 1H-ΝMR (DMSO) δ: 9.27 (t, J=6Hz, IH); 8.89 (d, J=6Hz, IH); 7.4-7.2 ( , 15H); 5 (m, IH); 4.5 (m, 4H); 4.3 (m, 2H); 3.67 (m, IH); 3.5-3.2 (m, 4H), 1.8 (m, 1H)1.6 (m, IH); 0.91 (t, J=7Hz, 3H); MS: (M+) 599.0, M(-) 598.18; N-r(S)-l-(l-Benzooxazol-2-yl-methanoyl)-butyl1-2-r2-(l,l-difluoro-methoxy)- benzylsulfonylmemyll-3-benzylsulfonyl-propionamide (Compound 54); 1H-ΝMR (DMSO) δ: 9.1 (t, J=6Hz, IH); 7.99 (d, J=8Hz, IH); 7.88 (d, J=8Hz, IH); 7.7-7.2 (m, 14H); 5.35 (m, IH); 4.6-4.4 (m, 5H); 3.7-3.3 (m, 5H); 1.9 (m, IH), 1.7 (m. 1H)1.45 (m, 2H); 0.90 (t, J=7Hz, 3H); MS: (M+) 599.0, M(-) 598.18; N-Cvanomethyl-3-(2-methyl-propane-l-sulfonyl)-2-(2-methyl-propane-l- sulfonylmethvD-propionamide (Compound 55); Η-ΝMR (DMSO) δ: 9.13 (t, J=5Hz, IH); 4.14 (m, 2H); 3.5-3.3 (m, 5H), 3.1-2.95 (m, 4H), 2.17 (h, J=7Hz, 2H)1.01 (d, J=7Hz, 12H); MS: (M+) 367.0, 366.13; Acetic acid (2S,3S)-3-(4-morpholm-4-yl-4-oxo-2-benzylsulfonylmethyl- butanoylammo)-4-oxo-azetidin-2-yl ester (Compound 58); *H ΝMR: (DMSO) 9.19 (d, J=5.9Hz, 1H)„ 8.94 (d, J=7.6Hz), 8.90 (d, J=7.6Hz), IH], 7.42-7.35 (m, 5H), 5.70 (m, IH), 4.60 (m, IH), 4.56-4.40 (m, 2H), 3.58-3.06 (m, 1 IH), 2.70-2.50 (m, 2H), 2.07 (s, 3H); MS: (M + +l) 482; N-Cvanomethyl-3-(2-methyl-tMazol-4-ylmethylsulfonyl)-2-benzyl-sulfonylmethyl- propionamide (Compound 59); Η ΝMR (DMSO): 9.14 (t, J=5 Hz, IH), 7.52 (s, IH), 7.38 (s, 5H), 4.64 (s, 2H), 4.53 (d, J=14 Hz, IH), 4.46 (d, J = 14 Hz, IH), 4.16 (d, J = 5 Hz, 2H), 3.5 (m, 5H), 2.63 (s, 3H); M=455.06, M(H+)=456.0; N-(3-Benzenesulfonylamino-2-oxo-propyl)-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide (Compound 60); 1H ΝMR: (DMSO) 8.46 (t, J=5.2Hz, IH), 7.97 (t, J=5.7Hz, IH), 7.79 (d, J=7Hz, 2H), 7.66-7.52 (m, 3H), 7.44-7.36 (m, 5H), 4.56-4.43 (m, 2H), 3.94 (d, J=5.2Hz, 2H), 3.84 (d, J=5.7Hz, 2H), 3.59-3.04 (m, 1 IH), 2.75- 2.55 (m, 2H); MS: (M + +l) 566; 3-Biphenyl-3-yl-N-cvanomethyl-2-r2-(l,l-difluoro-methoxy)-benzyl- sulfonylmethyll-propionamide (Compound 61); J H ΝMR: (DMSO) 8.86 (t, J = 5.4 Hz, IH), 7.70-7.10 (m, 13H), 7.12 (t, J = 73.7 Hz, IH), 4.46 (s, 2H), 4.13 (m, 2H), 4.10 (d, J = 5.6Hz, 2H), 3.57 (m, IH), 3.20-3.00 (m, 2H), 3.00-2.80 (m, 2H); MS: (M + +l) 499; (3'-{ 2-(Cvanomethyl-carbamoyl)-3-, 2- .1. l-difluoro-methoxy)-benzyl-sulfonyl1- propyl } -biphenyl-4-yl .-carbamic acid ethyl ester (Compound 62); *H ΝMR: (DMSO) 9.70 (s, IH), 8.84 (t, J = 5.4 Hz, IH), 7.55 (s, 4H), 7.50-7.15 (m, 8H), 7.11 (t, J = 73.7Hz, IH), 4.45 (s, 2H), 4.13 (m, 2H), 4.09 (d, J = 5.5Hz, 2H), 3.56 (m, IH), 3.20-3.00 (m, 2H), 2.95- 2.75 (m, 2H), 1.24 (t, J = 6.9 Hz, 3H); MS: (M + +l) 586; N-Cvanomethyl-2-r2-(l,l-difluoro-methoxy)-benzylsulfonylmethyl1-3-(4'- methylsulfonylamino-biphenyl-3-yl)-propionamide (Compound 63); X H ΝMR: (DMSO) 9.77 (s, IH), 8.79 (t, J = 5.4 Hz, IH), 7.57 (d, J=8.6, 2H), 7.50-7.00 (m, 8H), 7.27 (d, J=8.6 Hz, 2H), 7.06 (t, J = 73 Hz, IH), 4.40 (s, 2H), 4.04 (d, J = 5.6Hz, 2H), 3.51 (m, IH), 3.20-3.00 (m, 2H), 2.90-2.70 (m, 2H); MS: (M + +l) 592; 3-(3-Bromo-phenyl)-N-cvanomethyl-2-r2-(l,l-difluoro-methoxy)-phenyl- methylsulfonylmethvn-propionamide (Compound 64); 1HΝMR: (DMSO) 8.80 (t, J = 5.4 Hz, IH), 7.50-7.35 (m, 4H), 7.35-7.15 (m, 4H), 7.13 (t, J = 73 Hz, IH), 4.46 (s, 2H), 4.06 (d, J = 5.4Hz, 2H), 3.53 (m, IH), 3.20-3.00 (m, 2H), 2.90-2.70 (m, 2H); MS: (NT+1) 501; N-Cvanomethyl-2-((E)-3-phenyl-allyl)-3-benzylsulfonyl-proρionamide (Compound 65); 'HΝMR: (DMSO) 8.85 (t, J = 5.4 Hz, IH), 7.40-7.10 (m, 10H), 6.35 (d, J=15 Hz, IH), 6.15-5.95 (m, IH), 4.41 (s, 2H), 4.08 (d, J = 5.4Hz, 2H), 3.56-3.35 (m, 2H), 3.25-2.90 (m, 3H); MS: (M + +l) 383; and N-Cvanomethyl-3-benzylsulfonyl-2-(3-phenyl-propyl)-propionamide (Compound 66); ΗΝMR: (DMSO) 8.91 (t, J = 5.4Hz, IH), 7.45-7.10 (m, 10H), 4.41 (s, 2H), 4.08 (d, J = 5.4Hz, 2H), 3.30-2.80 (m, 3H), 2.34 (t, J = 7.4 Hz, 2H), 2.22-2.12 (m, 2H), 2.10-1.85 (m, 2H); MS: (M + +1) 385. EXAMPLE 11 4-Moφholin-4-yl-4-oxo-N-ri-(2-oxo-2-phenyl-acetyl)-pentyl1-2-benzylsulfonylmethyl- butyramide (Compound 67) 2-Amino-l-(2-phenyl-[l,3]dithian-2-yl)-hexan-l-ol, prepared as in reference 12, was coupled with 4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid, accordmg to the procedure outlined in example 8, resulting in N-{ l-[Hydroxy-(2-phenyl- [1,3] dithian-2-yl)-methyl] -pentyl } -4-moφholin-4-yl-4-oxo-2-benzylsulf onyl-methyl- butyramide as a mixture of diastereomers. N- { 1 - [Hydroxy-(2-phenyl-[ 1 ,3] d_thian-2-yl)-π_e thyl] -pentyl } -4-moφholin-4-yl-4- oxo-2-benzylsulfonylmethyl-butyramide (0.23 g, 0.35 mmol) in 9mL acetonitrile and 2.25mL water at 23°C was mixed with finely ground HgCl 2 (212 mg, 0.78 mmol) and finely ground calcium carbonate (90 mg, 0.89 mmol). The mixture was stirred for 25 minutes and then diluted with ethyl acetate. Water was added and the pH lowered to 6 by the addition of IN HCl. After separation, the organic layer was washed sequentially with water and brine (twice). The organics were dried with magnesium sulfate, concentrated and chromatographed on silica gel using a hexane-ethyl acetate gradient to afford 150 mg of N-[l-(l-Hydroxy-2-oxo-2-phenyl-ethyl)-pentyl]-4-moφholin-4-yl-4-oxo-2-phenyl- methylsulfonylmethyl-butyramide as a mixture of diastereomers (76% yield). N-[ 1 -( 1 -Hydroxy-2-oxo-2-phenyl-ethyl)-pentyl] -4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide was oxidized by methods described in the above examples resulting in 4-moφholin-4-yl-4-oxo-N- [ 1 -(oxo-phenyl-acetyl)-pentyll -2- benzylsulfonylmethyl-butyramide as a mixture of diastereomers: 'HΝMR: (DMSO), 8.9 (d, J = 6 Hz), 1/2H diastereomeric],, 8.86 (d, J = 6 Hz), 1/2H diastereomeric], 7.89-7.84 (m, 2H), 7.7-7.67 (m, IH), 7.56-7.5 (m, 2H), 7.4-7.3 (m, 5H), 4.56-4.54 (m, IH), 4.41-4.35 (m, 2H), 3.4-4.6 (m, 4H), 3.35-3.25 (m, 4H), 3.2-3.1 (m, 2H), 2.99 -2.95 (m, IH), 1.9-1.6 (m, 2H), 1.5-1.2 (m, 6H), 1.0-0.9 (m, 3H); MS: (M + + 1) 557. EXAMPLE 12 3-(4-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyrylamino)-4-oxo- pyrrolidine-1 -carboxylic acid tert-butyl ester 4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (120mg, 0.34mmol), 3-amino-4-hydroxy-pyrrolidine-l-carboxylic acid tert-butyl ester (150mg, 0.74mmol), prepared as in reference 13, EDC (0.3g, 1.6mmol), and HOBt (150mg, 0.96mmol) were combined. Dichloromethyl (lOmL) was added and then 4-methylmoφholine (0.5mL). The mixture was stirred at ambient temperature for 2hours. After dilution with ethyl acetate (200mL) the solution was washed with IN aqueous HCl (50mL), saturated aqueous NaHCO 3 (50mL) and brine (50mL), dried with MgSO and evaporated under vacuum. The crude 3-hydroxy-4-(4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyrylamino)- pyrrolidine-1 -carboxylic acid tert-butyl ester was dissolved in DMSO (5mL). Triethylamine (0.5mL) and then SO 3 pyridine complex (150mg) were added and the mixture was stirred at ambient temperature for 3 hours. After dilution with ethyl acetate (lOOmL), the solution was washed with water (50mL) and brine, dried with MgSO and evaporated under vacuum. The residue was purified by flash chromatography on silica gel. Eluent: 5% methanol in ethyl acetate. Yield: 40mg 3-(4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyrylamino)-4-oxo-p , yτrolidine-l -carboxylic acid tert-butyl ester as white solid as mixture of diastereomers; *H NMR: (DMSO) 8.80-8.66 (m, IH), 7.42- 7.34 (m, 5H), 4.52-4.41 (m, 2H), 4.34-4.20 (m, IH), 3.98-3.88 (m, IH), 3.82 (d, J=18.5Hz, IH), 3.70-3.05 (m, 13H), 2.70-2.52 (m, 2H), 1.41 (s, 9H); MS: (M+H) + 538. EXAMPLE 13 4-(4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyrylamino)-3-oxo-azepane-l- carboxylic acid benzyl ester (Compound 69) Sodium hydride (60% in mineral oil, lOg, 250mmol) was suspended in dry DMF. Allyl-carbamic acid benzyl ester (19. Ig, lOOmmol) was added drop wise at ambient temperature. After stirring for 5 minutes, 5-bromo-l-pentene (25g, 168mmol) was added drop wise. Stirring was continued at 50°C for 1 hour. The reaction was quenched with water and then partitioned between diethyl ether and water. The ether layer was washed with water and brine, dried with MgSO and evaporated under vacuum. Flash chromatography (ethyl acetate/hexane 1:9) gave 15.5g allyl-pent-4-enyl-carbamic acid benzyl ester. Allyl-pent-4-enyl-carbamic acid benzyl ester (15.5g, 59.8mmol) was dissolved in dichloromethyl andbis(tricyclohexylphosphine)benzylideneruthenium(IV) dichloride (lg) was added. The mixture was refluxed under a nitrogen atmosphere until TLC analysis showed complete reaction. The solvent was evaporated under vacuum and the residue was purified by flash chromatography (ethyl acetate/hexane 1:9). Yield: 7.8g 2,3,4,7- Tetrahydro-azepine-1 -carboxylic acid benzyl ester. To a solution of 2,3,4,7-tetrahydro-azepine-l-carboxylic acid benzyl ester (4.5g, 19.45mmol) in dichloromethyl (50mL) was added m-chloroperbenzoic acid (60mmol). The mixture was stirred at ambient temperature for 16 hours. Saturated aqueous K 2 CO 3 solution was added and the mixture was exttacted with dichloromethyl. The combined organic layers were washed with saturated aqueous NaHCO 3 and brine, dried with MgSO 4 and evaporated under vacuum. The crude epoxide was dissolved in a 8:1 methanol/water mixture (lOOmL). Ammonium chloride (3.2g, 60mmol) and sodium azide (3.9g, 60mmol) was added and the mixture was heated at 60°C for 48 hours. Most of the solvent was removed under vacuum. The residue was exttacted with ethyl acetate. The combined organic layers were washed with saturated aqueous NaHCO 3 (200mL) and brine (200mL), dried with MgSO 4 and evaporated under vacuum. Flash chromatography of the residue (hexane/ethyl acetate 3:1) gave 3.3g of 4-azido-3-hydroxy-azepane-l -carboxylic acid benzyl ester. To a solution of 4-azido-3-hydroxy-azepane-l-carboxylic acid benzyl ester (3.3g, 11.37mmol) in methanol (50mL) was added triethylamine (5mL) and 1,3-propanedithiol (3.42mL, 35mmol). The mixture was stirred at ambient temperature until TLC analysis showed complete consumption of the starting material. A white precipitate was removed by filtration and the filtrate was evaporated to dryness. The residue was triturated with a 1:1 hexane/diethyl ether mixture to remove excess dithiol and dried under vacuum. The crude 4-amino-3-hydroxy-azepane-l-carboxylic acid benzyl ester was coupled to 4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid and oxidized, as described above, to yield 4-(4-morpholin-4-yl-4-oxo-2-benzylsulfonylmemyl-butyrylamino)-3-oxo- azepane-1-carboxylic acid benzyl ester; 1HNMR: (DMSO) 8.46-8.42 (m, IH), 7.44-7.24 (m, 10H), 5.18-5.04 (m, 2H), 4.52-4.33 (m, 4H), 4.04-3.76 (m, 2H), 3.58-3.30 (m, IIH), 3.11-3.03 (m, IH), 2.96-2.78 (m, IH), 2.72-2.57 (m, IH), 1.84-1.55 (m,4H); MS: (M+H) + 600. EXAMPLE 14 N-(lJ-Dimethyl-2-oxazolor4.5-b1pyridin-2-yl-2-oxo-ethyl)-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide (Compound 70) To a stirred mixture of 4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (142mg, 0.4mmol), 2-amino-2-methyl-l-oxazolo[4,5-b]pyridin-2-yl-propan-l-one TFA salt (165mg), prepared as in reference 14, and HOBt (73mg, 0.45mmol) in MeCl 2 (5ml) was added EDC (115mg, 0.6mmol) and N-methylmoφholine (0.25ml) at room temperature. After stirring for 14 hours, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated NaHCO 3 , brine, dried with MgSO and concenttated. The residue was purified by silica gel column chromatography to yield 92 mg of N-{ l-[(5-Emyl-[l,3,4]oxadiazol-2-yl)-hy<_roxy-memyl]-butyl}-4-moφholin-4-yl- 4-oxo-2-benzylsulf onyl e thyl-bu tyramide. This amide was tteated with Dess-Martin periodinane (125.6mg, 0.254mmol) at room temperature. After stirring for 1 hour, 5ml of saturated Νa S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO and concenttated. The residue was purified with silica gel column chromatography to yield 31 mg of N-(l , l-dimethyl-2-oxazolo, 4,5- b]pyridin-2-yl-2-oxo-ethyl)-4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyramide; H 1 ΝMR(DMSO-d): 9.36QH, s, NH), 8.68(1H, d, J=4.7Hz), 8.34(1H, d, J=8.42Hz), 7.62QH, dd, J=4.7Hz, J=8.42Hz), 7.4-7.4(5H, m), 4.41-4.3(2H, s), 3.5-3Q2H, m), 2.2- 2.1(1H, m), 1.6(3H, s), 1.51(3H, s); MS: 541.4(M-1), 543.4(M+1). EXAMPLE 15 N-r 1 -(5 -Ethyl- r 1 ,3 ,41 oxadiazole-2-carbonyl)-butyl1 -4-moφholm-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide (Compound 71) To a stirred mixture of 4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl- butyric acid (177.7mg, 0.5mmol), 2-amino-l-(5-ethyl-l,3,4-oxadiazole-2-yl)-l-pentanol HCl salt (117.5mg), and HOBt (91.8mg, 0.6mmol) in MeCl 2 (5ml), was added EDC (144mg, 0.75mmol) andN-methylmoφholine (0.3ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated NaHCO 3 , brine, dried with MgSO 4 and concenttated to yield 240 mg of crude product (MS: 536(M-1), 538.4(M+1)). Without further purification, the crude product was treated with Dess-Martin periodinane (334mg, 0.67mmol) at room temperature in 5mL of MeCl . After stirring for 1 hour, 5mls of saturated Na 2 S 2 O 3 - NaHCO 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO 4 and concenttated. The residue was purified with silica gel column chromatography to yield 110 mg of N-ri-(5-ethyl- ri,3,41oxadiazole-2-carbonyl)-butyl1-4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl- butyramide: H 1 ΝMR(DMSO-d): 8.84(1/2H, d, NH, diastereomeric), 8.78(1/1H, d, NH, diastereomeric), 7.45-7.2(5H, m), 5.05-4.9(lH, m), 4.48-4.3(2H,m), 3.6-3.4(4H, m), 3.4- 3.2(4H, m), 3.1-2.4(6H, m), 1.9-1.75(1H, m), 1.7-1.55(2H, m), 1.25-1.2(2H, m), 1.2- 1.1(3H, m), 0.9-0.8(3H, m); MS: 534M-1), 535.8(M+1). EXAMPLE 16 N-.1 - , 5-Ethyl-r 1.3.41 oxadiazole-2-carbonyl)-butyl1-4-oxo-2-benzylsulfonyl-methyl-4- piperidin- 1 -yl-butyramide (Compound 72) ' To a stirred mixture 4-oxo-2-benzylsulfonylmethyl-4-piperidin-l-yl-butyric acid (176.5mg, 0.5mmol), 2-amino-l-(5-ethyl-l,3,4-oxadiazole-2-yl)-l-pentanol HCl salt (117.5mg), and HOBt (91.8mg, 0.6mmol) in MeCl 2 (5ml), was added EDC (144mg, 0.75mmol) and N-methylmoφholine (0.3ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. Trie organic layer was washed with saturated NaHCO 3 , brine, dried with MgSO 4 and concentrated to yield 270mg of crude product; MS: 534.KM-1), 535.7(M+1). The amide was then tteated with Dess-Martin periodinane (378.7mg, 0.675mmol) at room temperature in 5 ml of MeCl 2 . After stirring for 1 hour, 5ml of saturated Na 2 S 2 O - NaHCO 3 were added. After a further 0.5 hours, the reaction mixture was extracted with ethyl acetate, washed with brine, dried with MgSO 4 and concentrated. The residue was purified with silica gel column chromatography to yield 165 mg of N-fl-(5-Ethyl- ri,3,41oxadiazole-2-carbonyl)-butyl1-4-oxo-2-benzyl-sulfonyl-methyl-4-piperidin-l-yl- butyramide; H 1 ΝMR (DMSO-d): 8.85(1/2H, d, ΝH, diastereomeric), 8.78(1/2, d, ΝH, diastereomeric), 7.4-7.2(5H, m), 5.1-4.9(1H, m), 4.5-4.3(2H,m), 3.5-3.2(8H, m), 3.1- 2.6(1H, m), 2.9(2H, ), 1.9-1.6(2H, m), 1.6-1.2(8H, ), 1.24(3H, m), 0.9-0.8(3H, m); MS: 531.6(M-1), 533.4(M+1). EXAMPLE 17 N-ri-(5-Ethyl-ri,3.41oxadiazol.e-2-carbonyl)-butvn-4-oxo-2-benzylsulfonyl-methyl-4- pyrrolidin- 1 -yl-butyramide (Compound 73) To a stirred mixture 4-cyclopentyl-4-oxo-2-benzylsulfonylmethyl-butyric acid (169.5mg, 0.5mmol), 2-amino-l-(5-ethyl-l,3,4-oxadiazole-2-yl)-l-pentanol HCl salt (117.5mg), and HOBt (91.8mg, O.όmmol) in MeCl 2 (5ml), was added EDC (144mg, 0.75mmol) and N-methylmoφholine (0.3ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated NaHCO 3 , brine, dried with MgSO 4 and concentrated to yield 240 mg of crude product. The crude product was tteated with Dess-Martin periodinane (343mg, 0.693mmol) at room temperature in 5mls of MeCl 2 . After stirring for 1 hour, 5mls of saturated Na 2 S 2 O 3 -NaHCO 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO 4 and concenttated. The residue was purified with silica gel column chromatography to yield 145 mg of N-l " 1 -(5-Ethyl- r 1 ,3 ,41 oxadiazole-2-carbonyl)-bu tyll -4-oxo-2-benzylsulf onyl-methyl-4- pyrrolidin-1-yl-butyramide: H 1 ΝMR(DMSO-d): 8.85Q/2H, d, NH, diastereomeric), 8.78Q/2H, d, NH, diastereomeric), 7.5-7.3(5H, m), 5.1-4.95(1H, m), 4.5-4.3(2H,m), 3.5- 3.2(8H, m), 3.2-3(lH, m), 2.82(2H, m), 2-1.8(6H, m), 1.6-1.3(2H, m), 1.24(3H, m), 0.9- 0.8(3H, m); MS: 518.2(M-1), 519.7(M+1). EXAMPLE 18 N- r 1 -(5 -Me thoxymethyl- r 1 ,3 ,41 oxadiazole-2-carbonyl)-propyl1 -4-moφholin-4-yl-4- oxo-2-benzylsulfonylmethyl-butyramide (Compound 74) To a stirred mixture of 4-moφholm-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (230mg, O.65mmol), 2-amino-l-(5-methoxymethyl-[l,3,4]oxadiazol-2-yl)-butan-l- one TFA salt (204mg), prepared as in reference 15, and HOBt (119mg, 0.78mmol) in MeCl 2 (5ml), was added EDC (187mg, 0.98mmol) and N-methylmoφholine (0.35ml) at room temperature. After stirring for 14 hours, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated NaHCO 3 , brine, dried with MgSO and concenttated to yield 82mg of N-{ l-[Hydroxy-(5-methoxymefhyl- [ 1 ,3 ,4] oxadiazol-2-yl)-methyl]-propyl } -4-moφholin-4-yl-4-oxo-2-benzylsulfonyl-methyl- butyramide; MS: 537.6(M-1), 539.8(M+1). This amide then was tteated with Dess-Martin periodinane (11 lmg, 0.149mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S O 3 -ΝaHCO 3 was added. After a further 0.5 hours, the reaction mixture was extracted with ethyl acetate, washed with brine, dried with MgSO and concenttated. The residue was purified with silica gel column chromatography to yield 13mgs of N- \ 1 -(5 -Methoxymethyl- ri,3.41oxadiazole-2-carbonyl)-propyl1-4-morpholin-4-yl-4-oxo-2-benzylsulfonyl-methyl- butyramide; H 1 ΝMR(CDC1 3 ): 7.8, 7.5(lH, d,d NH, diastereomeric), 7.4-7.2(5H,m), 5.3- 5.1(1H, m), 4.6(2H, s, OCH 2 ), 4.3-4.1(3H, m), 3.8-3.1Q3H, m), 3-2.4(2H, m), 2.2-1.5(2H, m), 0.95(3H, t); MS: 535.7(M-1), 537.5(M+1). EXAMPLE 19 N-ri-(5-Methoxymethyl-ri,3.41oxadiazole-2-carbonyl)-propyll-4-oxo-2- benzylsulf onylmethyl-4-piρeridin- 1 -yl-butyrarnide (Compound 75) To a stirred mixture of 4-oxo-2-berιzylsulfonylmethyl-4-piperidin-l-yl-butyric acid (229mg, 0.65mmol), 2-amino-l-(5-methoxymethyl-l,3,4-oxadiazole-2-yl)-l-propanol TFA salt (204mg), prepared as in reference 15, and HOBt (119mg, 0.78mmol) in MeCl 2 (5ml), was added EDC (187mg, 0.98mmol) and N-methylmoφholine (0.35ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated NaHCO 3 , brine, dried with MgSO 4 and concentrated to yield 130 mg of N-{ l-[hydroxy-(5-mefhoxymethyl-[l,3,4]oxadiazol-2- yl)-methyl] -propyl } -4-oxo-2-benzylsulfonylmethyl-4-piperidin- 1 -yl-butyramide; MS : 535.4(M-1), 537.7(M+1). The amide then was tteated with Dess-Martin periodinane (180mg, 0.364mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was extracted with ethyl acetate, washed with brine, dried with MgSO 4 and concenttated. The residue was purified with silica gel column chromatography to yield 26mgs of N- F 1 -(5-Methoxymethyl- ri.3,41 oxadiazole-2-carbonyl)-propyl1 -4-oxo-2-benzylsulf onylmethyl-4-piperidin- 1 -yl- butyramide; H 1 NMR(CDC1 3 ): 8, 7/7(lH, d,d, NH, diastereomeric), 7.4-7.2(5H, m), 5.3- 5.1(1H, m), 4.6(2H, s, OCH 2 ), 4.3-4J(3H, m), 3.8-3.2(9H, m), 3-2.4(2H, m), 2.2-1.4(8H, m), 0.95(3H, t); MS: 535.7(M+1). EXAMPLE 20 N- f 1 -(5-Methoxymethyl- f 1 ,3 ,41 oxadiazole-2-carbonyl)-propyl1 -4-oxo-2- benzylsulfonylmethyl-4-pyrrolidin- 1 -yl-butyramide (Compound 76) 0 To a stirred mixture of 4-oxo-2-benzylsulfonylmethyl-4-pyπolidin-l-yl-butyric acid (220mg, 0.65mmol), 2-amino-l-(5-methoxymethyl-l,3,4-oxadiazole-2-yl)-l-propanol TFA salt (204mg), prepared as in reference 15, and HOBt (119mg, 0.78mmol) in MeCl 2 (5ml), was added EDC (187mg, 0.98mmol) and N-methylmoφholine (0.35ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated ΝaHCθ 3 , brine, dried with MgSO 4 and concenttated to yield 84 mg of N-{ l-[Hydroxy-(5-methoxymethyl-[l,3,4]oxadiazol-2- yl)-methyl]-propyl}-4-oxo-2-benzylsulfonylmethyl-4-pyrrolidin-l-yl-but ramide. Without further purification, the crude product was used for next reaction; MS: 521.6(M-1), 523.2(M+1). This amide was treated with Dess-Martin periodinane (114mg, 0.153mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO and concenttated. The residue was purified with silica gel column chromatography to yield 17 mg of N~ri-(5-Mefhoxymethyl- ri,3,41oxadiazole-2-carbonyl)-propyl]-4-oxo-2-benzylsulfonylmethyl-4-pyrrolidin-l-yl- butyramide: H 1 ΝMR(CDC1 3 ): 8.2, 8(1H, d-d, NH, diastereomeric), 7.6-7.2(5H, m), 5.3- 5.1QH, m), 4.6(2H, s, OCH 2 ), 4.3-4.1(3H, m), 3.8-3.2(9H, m), 3-2.4(2H, m), 2.2-1.4(6H, m), 0.95(3H, t); MS:519.6(M-1), 521.6(M+1). EXAMPLE 21 4-Morpholin-4-yl-4-oxo-2-benzylsulf onylme thyl-N- [ 1 -(5-phenyl- r 1 ,3 ,41 oxadiazole-2- carbonyD-propyll -butyramide (Compound 77) To a stirred mixture of 4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (177mg, 0.5mmol), 2-amino-l-(5-phenyl-[l,3,4]oxadiazol-2-yl)-l-butanol TFA salt (175mg), prepared as in reference 16, and HOBt (92mg, O.όmmol) in MeCl 2 (5ml), was added EDC (144mg, 0.75mmol) andN-methylmoφholine (0.35ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO and concenttated to yield 308 mg of N-{ l-[Hydroxy-(5-phenyl-[l,3,4]oxadiazol-2-yl)-methyl]- propyl }-4-moφholin-4-yl-4-oxo-2-benzylsulfonylmemyl-butyramide. Without further purification, the crude product was used for next reaction; MS: 569.6(M-1), 571.4(M+1). This amide was tteated with Dess-Martin periodinane (371mg, 0.75mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Na 2 S 2 O 3 -NaHCO 3 were added. After a further 0.5 hours, the reaction mixture was extracted with ethyl acetate, washed with brine, dried with MgSO 4 and concenttated. The residue was purified with silica gel column chromatography to yield 224 mg of 4-morpholin-4-yl-4-oxo-2- benzylsulfonylmethyl-N-ri-(5-phenyl-ri,3,41oxadiazole-2-carbonyl)-propyll-butyramide; H 1 ΝMR(DMSO-d): 8.9, 8.84 (IH, d, d, NH, diastereomeric), 8.1-8(2H, m), 7.7-7.6(3H, m), 7.4-7.3(5H, m),5.1-4.9(lH, m), 4.5-4.3(2H, m), 3.6-3.3(1 IH, m), 3.12-3(1H, m), 2.65- 2.5(1H, m) , 2-1.9(lH, m), 1.8-1.7QH, m), 0.96(3H, t); MS: 567.6(M-1), 569.4(M+1). EXAMPLE 22 4-Oxo-2-benzylsulfonylmefhyl-N-ri-(5-phenyl-ri,3,41oxadiazole-2-carbonyl)-propyl1- 4-piperidin- 1 -yl-butyramide (Compound 78) To a stirred mixture of 4-oxo-2-benzylsuIfonylmethyl-4-piperidin-l-yl-butyric acid (177mg, 0.5mmol), 2-amino-l-(5-ρhenyl-[l,3,4]oxadiazol-2-yl)-l-butanol TFA salt (175mg) , prepared as in reference 16, and HOBt (92mg, 0.6mmol) in MeCl 2 (5ml), was added EDC (144mg, 0.75mmol) and N-methylmoφholine (0.35ml) at room temperature. After stirring for 14 hours, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO and concenttated to yield 284 mg of N-{ l-[Hydroxy-(5-phenyl-[l,3,4]oxadiazol-2-yl)-methyl]- propyl}-4-oxo-2-henylmethylsulfonylmemyl-4-piperidin-l-yl-butyrarnide. Without further purification, the crude product was used for next reaction; MS: 567.6(M-1), 569.6(M+1). This amide was treated with Dess-Martin periodinane (371mg, 0.75mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO 4 and concentrated. The residue was purified with silica gel column chromatography to yield 237 mg of4-oxo-2-benzylsulfonylmemyl-N-,l-(5-phenyl- ri-3,41 oxadiazole-2-carbonyl)-propyl1-4-piperidin- 1 -yl-butyramide; H 1 ΝMR (DMSO-d): 8.9, 8.84 (IH, d, d, ΝH, diastereomeric), 8.1-8(2H, m), 7.7-7.6(3H, m), 7.4-7.3(5H, m),5.1-4.9(lH, m), 4.5-4.3(2H, m), 3.4-3.1(7H, m), 3.12-3(1H, m), 2.65-2.5(lH, m) , 2- 1.9(1H, m), 1.8-1.7(1H, m), 1.6-1.2(6H, m), 0.96(3H, t); MS: 565.4(M-1), 567.6(M+1). EXAMPLE 23 4-Oxo-2-benzylsulfonylmethyl--\.-ri-(5-ρhenyl-ri,3,41oxadiazole-2-carbonylV propyπ-4-pyHθIidin-l-yl-butyramide (Compound 79) To a stirred mixture of 4-Oxo-2-benzylsulfonylmethyl-4-pyrcolidin-l-yl-butyric acid (170mg, 0.5mmol), 2-amino-l-(5-phenyl-[l,3,4]oxadiazol-2-yl)-l-butanol TFA salt (175mg) , prepared as above, and HOBt (92mg, 0.6mmol) in MeCl 2 (5ml), was added EDC (144mg, 0.75mmol) andN-methylmoφholine (0.35ml) at room temperature. After stirring for 14 hours, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO 4 and concenttated to yield 280 mg of N-{ l-[Hydroxy-(5-phenyl-[l,3,4]oxadiazol-2-yl)-methyl]-ρropyl}-4-oxo-2- henylmethylsulfonylmethyl-4-pyrrolidin- 1 -yl-butyramide. Without further purification, the crude product was used for next reaction; MS: 553.6(M-1), 555.4(M+1). This amide was treated with Dess-Martin periodinane (371mg, 0.75mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was extracted with ethyl acetate, washed with brine, dried with MgSO 4 and concenttated. The residue was purified with silica gel column chromatography to yield 200mg of4-oxo-2-benzylsulfonylmethyl-N-[l-(5-phenyl- ri,3.41oxadiazole-2-carbonyl)-propyn-4-pyrrolidm-l-yl-butyramide: H 1 ΝMR (DMSO-d): 8.9, 8.84 (IH, d, d, ΝH, diastereomeric), 8.1-8(2H, m), 7.7-7.6(3H, m), 7.4-7.3(5H, m),5.1-4.9(lH, m), 4.5-4.3(2H, m), 3.4-3.1(7H, m), 3.12-3(1H, m), 2.65-2.5QH, m) , 2.1- 1.6(6H, m), 0.96(3H, t); MS: 551.6(M-1), 553.6(M+1). EXAMPLE 24 4-Morpholip-4-yl-N-ri-(oxazolor4,5-b1pyridine-2-carbonyl)-propyl1-4-oxo-2- benzylsulfonylmethyl-butyramide (Compound 80) To a stirred mixture of 4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (177mg, 0.5mmol), 2-amino-l-(5-phenyl-[l,3,4]oxadiazol-2-yl)-l-butanol TFA salt (175mg), prepared as in reference 17, and HOBt (92mg, 0.6mmol) in MeCl 2 (5ml), was added EDC (144mg, 0.75mmol) and N-methylmoφholine (0.35ml) at room temperature. After stirring for 14 hours, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO and concenttated to yield 308 mg of N-[l-(Hydroxy-oxazolo[4,5-b]pyridin-2-yl-methyl)- propyl]-4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethylHbutyramide; MS: 543.6 (M-l), 545.6(M+1) This amide was tteated with Dess-Martin periodinane (371mg, 0.75mmol) atroom temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was extracted with ethyl acetate, washed with brine, dried with MgSO and concenttated. The residue was purified with silica gel column chromatography to yield 224 mg of 4-moφholin-4-yl-N- , 1 -(oxazolo, 4,5- blpyridme-2-carbonyl)-propyl1-4-oxo-2-benzylsulfonylmethyl-butyramide; H 1 ΝMR (DMSO-d): 8.96, 8.85(1H, d,d, ΝH, diastereomeric), 8.75-8.7QH, m), 8.42-8.3(lH, m), 7.7-7.6(lH, m), 7.4-7.3(5H, m), 5.15-5.04(1H, m), 4.5-4.3(2H, m), 3.6-3.2Q1H, m), 3.15- 3.0(1H, m), 2.7-2.5(lH, m), 2.1-1.9QH, m), 1.8-1.7(1H, m), 0.98(3H, t); MS: 541.2(M-1), 543.2(M+1). EXAMPLE 25 N-ri-(Oxazolor4,5-b1pyridine-2-carbonyl)-propyll-4-oxo-2-benzylsulfonγl-methyl-4- piperidin- 1 -yl-butyramide (Compound 81) To a stiπed mixture of 4-oxo-2-benzylsulfonylmethyl-4-piperidin-l-yl-butyric acid (177mg, 0.5mmol), 2-amino-l-(5-phenyl-[l,3,4]oxadiazol-2-yl)-l-butanol TFA salt (175mg) , prepared as in reference 17, and HOBt (92mg, 0.6mmol) in MeCl 2 (5ml), was added EDC (144mg, 0.75mmol) and Ν-methylmoφholine (0.35ml) at room temperature. After stirring for 14 hours, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO 4 and concenttated to yield 284 mg of N-[l-(hydroxy-oxazolo[4,5-b]pyridin-2-yl-methyl)- propyl]-4-oxo-2-henylmethylsulfonylmethyl-4-piperidin-l -yl-butyramide; MS: 541.6 (M- 1), 543.4(M+1). This amide was treated with Dess-Martin periodinane (371mg, 0.75mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCθ 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO 4 and concentrated. The residue was purified with silica gel column chromatography to yield 237 mg of N-ri-(Oxazolor4,5-b1pyridine-2-carbonyl)- propyll -4-oxo-2-benzylsulf onyl-methyl-4-piperidrn- 1 -yl-butyramide; H 1 ΝMRDMSO-d): 8.93, 8.83QH, d,d, ΝH, diastereomeric), 8.75-8.72QH, m), 8.4-8.37QH, m), 7.7-7.6(lH, m), 7.4-7.3(5H, m), 5.15-5QH, m), 4.5-4.3(2H, m), 3.45-3.2(9H, m), 3.1-3(1H, m), 2.67- 2.5(lH, m), 2.1-1.9(lH, m), 1.84-1.7(lH,m), 1.6-1.5(2H,m), 1.5-1.3(4H,m), 0.98(3H,t); MS: 539.4(M-1), 541.2(M+1). EXAMPLE 26 N-ri-(Oxazolor4,5-b1pyridine-2-carbonyl)-propyl1-4-oxo-2-benzylsulfonyl-methyl-4- pyrrolidin- 1 -yl-butyramide (Compound 82) To a stirred mixture of 4-oxo-2-benzylsulfonylmethyl-4-pyrrolidin-l-yl-butyric acid (170mg, 0.5mmol), 2-amino-l-(5-phenyl-[l,3,4]oxadiazol-2-yl)-l-butanol TFA salt (175mg) , prepared as in reference 17, and HOBt (92mg, 0.6mmol) in MeCl 2 (5ml), was added EDC (144mg, 0.75mmol) andN-methylmoφholine (0.35ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO 4 and concenttated to yield 280 mg of N-[l-(Hydroxy-oxazolo[4,5-_>]pyridin-2-yI-methyl)- propyl]-4-oxo-2-henylmethylsulfonylmethyl-4-pyrrolidin- 1-yl-butyramide. Without further purification, the crude product was used for next reaction; MS: 527.6(M-1), 529.4(M+1). This amide was tteated with Dess-Martin periodinane (371mg, 0.75mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO 4 and concenttated. The residue was purified with silica gel column chromatography to yield 200mg of N-ri-(Oxazolor4,5-b1pyridine-2-carbonyl)- propyll-4-oxo-2-benzylsulfonyl-methyl-4-pyrrolidin-l-yl-butyramide: H 1 ΝMR (DMSO- d): 8.96, 8.87(1H, d,d, ΝH, diastereomeric), 8.75-8.72(lH, m), 8.45-8.3(lH, m), 7.7- 7.6(1H, m), 7.45-7.3(5H, m), 5.2-5QH, m), 4.5-4.3(2H, m), 3.5-3.15(7H, m), 3.15-3(1H, m), 2.55-2.4(lH, m), 2.1-1.95(1H, m), 1.9-1.6(5H, m), 0.98(3H, t); MS: 525.2(M-1), 526.8(M+1). EXAMPLE 27 4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-ri-(5-pyridin-4-yl- [l,3,41oxadiazole-2-carbonyl)-propyl1-butyramide (Compound 83) To a stirred mixture of 4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (106.5mg, 0.3mmol), 2-Amino-l-(5-pyridin-4-yl-[l,3,4]oxadiazol-2-yl)-butan-l-ol TFA salt (105mg), prepared as in reference 18, and HOBt (55mg, 0.36mmol) in MeCl 2 (5ml), was added EDC (86.4mg, 0.45mmol) and Ν-methylmoφholine (0.25ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO 4 and concenttated, yield 176 mg of N-{ l-[hydroxy-(5-pyridin-4-yl-[l,3,4]oxadiazol-2-yl)- methyl] -propyl } -4-oxo-2-benzylsulf onylmethyl-4-piperidin- 1 -yl-butyramide. MS : 568.4(M-1), 570(M+1) This amide was treated with Dess-Martin periodinane (222.7mg, 0.45mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 θ 3 -ΝaHCθ 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO 4 and concenttated. The residue was purified with silica gel column chromatography to yield 84mg of 4-moφholin-4-yl-4-oxo-2- benzylsulf onylmethyl-N- , 1 -(5-pyridm-4-yl- r 1 ,3 ,41 oxadiazole-2-carbonyl)-propyl1- butyramide; H 1 ΝMR(DMSO-d): 8.95-8.85(3H, m), 8.1-8(2H, m), 7.44-7.3(5H, m), 5- 4.9QH, m), 4.5-4.3(2H, m), 3.4-3.(8H, m), 2J-2.5QH, m), 2.05-1.9(1H, m), 1.8-1.6(1H, m), 1.6-1.2(6H, m), 0.98(3H, t); MS: 566.6(M-1), 568.6(M+1). EXAMPLE 28 4-Oxo-2-benzylsulfonylmethyl-4-piperidin-l-yl-N-[l-(5-pyridm-4-yl-[l,3,41oxadiazole- 2-carbonyl)-propyl1 -butyramide (Compound 84) To a stirred mixture of 4-oxo-2-benzylsulfonylmethyl-4-piperidin-l-yl-butyric acid (105.9mg, 0.3mmol), 2-amino-l-(5-pyridin-4-yl-[l,3,4]oxadiazol-2-yl)-butan-l-ol TFA salt (105mg) , prepared as in reference 18, and HOBt (55mg, 0.36mmol) in MeCl 2 (5ml), was added EDC (86.4mg, 0.45mmol) andN-methylmoφholine (0.25ml) at room temperature. After stirring for 14 hours, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO and concentrated to yield 176mg of N-{l-[Hydroxy-(5-pyridm-4-yl-[l,3,4]oxadiazol-2-yl)- methyl] -propyl } -4-moφholin-4-yl-4-oxo-2-benzylsulfonyl-methyl-butyramide; MS : 570.2(M-1), 572(M+1). This amide was treated with Dess-Martin periodinane (222.7mg, 0.45mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO 4 and concenttated. The residue was purified with silica gel column chromatography to yield 78 mg of 4-oxo-2-benzylsulfonyl-methyl-4- piperidin-l-yl-N-ri-(5-pyridm-4-yl-ri,3.41oxadiazole-2-carbonyl)-propyl1-butyramide;H 1 ΝMR(DMSO-d): 9.0-8.85(3H, m), 8.1-8(2H, m), 7.44-7.3(5H, m), 5-4.9(lH, m), 4.5- 4.3(2H, m), 3.6-3.2(llH, m), 3.15-3.05(1H, m), 2.7-2.5(lH, m), 2.05-1.9(lH, m), 1.8- 1.7(1H, ), 0.96(3H, t); MS: 568.6(M-1), 570.6(M+1). EXAMPLE 29 4-Oxo-2-benzylsulfonylmethyl-N-ri-(5-pyridin-4-yl-ri,3,41oxadiazole-2-carbonyl)- propyll -4-pyrrolidin- 1 -yl-butyramide (Compound 85) To a stirred mixture of 4-oxo-2-benzylsulfonylmethyl-4-pyrrolidin-l-yl-butyric acid (102mg, 0.3mmol), 2-amino-l-(5-ρyridin-4-yl-[l,3,4]oxadiazol-2-yl)-butan-l-olTFA salt (105mg) , prepared as in reference 18, and HOBt (55mg, 0.36mmol) in MeCl 2 (5ml), was added EDC (86.4mg, 0.45mmol) and N-methylmoφholine (0.25ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO 4 and concenttated to yield 210 mg of N-{l-[Hydroxy-(5-pyridin-4-yl-[l,3,4]oxadiazol-2-yl)- methyl]-propyl}-4-oxo-2-benzylsulfonylmethyl-4-pyrrolidin-l-yl-butyramide. MS: 554.2(M-1), 555.8(M+1). This amide was tteated with Dess-Martin periodinane (222.7mg, 0.45mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO and concenttated. The residue was purified with silica gel column chromatography to yield 102 mg of 4-Oxo-2-benzylsulfonylmethyl-N-ri-(5- pyridm-4-yl-ri,3,41oxadiazole-2-carbonyl)-propyl1-4-pyπolid_α-l-yl-butyramide; H 1 ΝMR (DMSO-d): 9.0-8.85(3H, m), 8.1-8(2H, m), 7.44-7.3(5H, m), 5.05-4.9(lH, m), 4.55- 4.35(2H, m), 3.4-3.(8H, m), 2.6-2.4(lH, m), 2.05-1.9(lH, m), 1.9-1.6(5H, m), 0.96(3H, t); MS: 552.6(M-1), 554.6(M+1). EXAMPLE 30 4-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-ri-(5-pyridin-3-yl- ri,3,41oxadiazole-2-carbonyl)-propyl1-butyramide (Compound 86) To a stirred mixture of 4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (177.7mg, 0.5mmol), 2-amino-l-(5-pyridin-3-yl-[l,3,4]oxadiazol-2-yl)-butan-l-ol TFA salt (180mg), prepared as in reference 19, and HOBt (92mg, 0.6mmol) in MeCl 2 (5ml), was added EDC (144mg, 0.75mmol) and N-methylmoφholine (0.25ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO 4 and concentrated, yield 210 mg of N-{ l-[Hydroxy-(5-pyridin-3-yl-[l,3,4]oxadiazol-2-yl)- methyl] -propyl } -4-moφholin-4-yl-4-oxo-2-benzylsulf onylme thyl-bu tyramide. Without further purification, the crude product was used for next reaction; MS: 570.4(M-1), 572.4(M+1). This amide was treated with Dess-Martin periodinane (277mg, 0.56mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was extracted with ethyl acetate, washed with brine, dried with MgSO and concenttated. The residue was purified with silica gel column chromatography to yield 110 mg of 4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-N-ri-(5-pyridin-3-yl-ri,3,41oxadiazole-2-carbonyl)-propyl1- butyramide; H 1 ΝMR(DMSO-d: 9.23(1H, s), 8.94, 8.88(1H, d,d, NH, diastereomeric), 8.87-8.8(lH, m), 8.46-8.4(lH, m), 7.7-7.6(lH, m), 7.4-7.25(5H, m), 5.05-4. ' 9(lH, m), 4.55- 4.3(2H, m), 3.6-3.15(llH, m), 3.14-3(1H, m), 2.7-2.5(lH, m), 2.05-1.9(lH, m), 1.8- 1.65(1H, ), 0.98(3H, t); MS: 568.5(M-1), 570.3(M+1). EXAMPLE 31 N-ri-(Benzooxazole-2-carbonyl)-propyll-4-oxo-2-benzylsulfonylmethyl-4-piperidin-l- yl-butyramide . (Compound 87) To a stirred mixture of 4-oxo-2-ber_zylsulfonylmethyl-4-piperidin-l-yl-butyric acid (141mg, 0.4mmol), 2-amino-l-benzooxazol-2-yI-butan-l-ol TFA salt. (129mg) , prepared as in reference 20, and HOBt (74mg, 0.48mmol) in MeCl 2 (5ml), was added EDC (115mg, 0.6mmol) and Ν-methylmoφholine (0.25ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO and concenttated to yield 157mg of N- [1 -(Benzooxazol-2-yl-hydroxy-methyl)-propyl] -4-oxo-2-enylme thylsulf onylmethyl-4- piperidin-1-yl-butyramide. Without further purification, the crude product was used for next reaction; MS: 540.4(M-1), 542.6(M+1). This amide was tteated with Dess-Martin periodinane (215.3mg, 0.435mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was extracted with ethyl acetate, washed with brine, dried with MgSO and concentrated. The residue was purified with silica gel column chromatography to yield 103.3 mg of N-\ 1 - ( Benzooxazole-2-carbonyl)-propyl1 -4- oxo-2-bepzylsulfonylmethyl-4-piperidin-l-yl-butyramide; H 1 NMR(DMSO-d): 8.84, 8.76(1H, d,d, J=5.6Hz, J=6.4Hz, NH, diastereomeric), 8.02-7.96QH, ), 7.92-7.86(lH, m), 7.68-7.62(lH, m), 7.58-7.52(lH, m), 7.44-7.32(5H, m), 5.24-5.12(1H, m), 4.52- 4.38(2H, m), 3.5-3.22(7H, m), 3.12-3.02(1H, m), 2.64-2.52QH, m), 2.04-1.94(1H, m), 1.8-1.68(1H, m), 1.6-1.48(2H, m), 1.48-1.32(4H, m), 0.98(3H, t, J=7.6Hz); MS: 540.4(M+1). EXAMPLE 32 N- r 1 -(Benzooxazole-2-carbonyl)-propyl1 -4-oxo-2-benzylsulf onylmethyl-4-pyrrolidin- 1 - yl-butyramide (Compound 88) To a stirred mixture of 4-oxo-2-benzylsulfonylmethyl-4-pyrrolidin-l-yl-butyric acid (135.6mg, 0.4mmol), 2-amino-l-benzooxazol-2-yl-butan-l-ol TFA salt (129mg) , prepared as in reference 20, and HOBt (73.4mg, 0.48mmol) in MeCl 2 (5ml), was added EDC (115.2mg, 0.6mmol) and N-methylmoφholine (0.25ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO 4 and concentrated to yield 260 mg of N-[l-(Benzooxazol-2-yl-hydroxy-methyl)-propyl]-4-oxo-2- henylme thylsulfonylmethyl-4-pyrrolidin- 1 -yl-butyramide. Without further purification, the crude product was used for next reaction; MS: 526.6(M-1), 528.6(M+1). This amide was tteated with Dess-Martin periodinane (215mg, 0.435mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was extracted with ethyl acetate, washed with brine, dried with MgSO and concenttated. The residue was purified with silica gel column chromatography to yield 199mg of N- f 1 - ( Benzooxazole-2-earbonyl)-propyl1 -4- oxo-2-benzylsulfonylmethyl-4-pyrrolidin-l-yl-butyramide; H 1 NMR(DMSO-d): 8.87, 8.79(1H, d,d, NH, J=6Hz, J=6.4Hz, diastereomeric), 8.04-7.96(lH, m), 7.92-7.86QH, m), 7.68-7.62QH, m), 7.58-7.5(lH, m), 7.44-7.32(5H, m), 5.25-5.14(lH, m), 4.52-4.38(2H, m), 3.5-3.04(7H, m), 3.03-3.01(lH, m), 2.52-2.4(lH, m), 2.05-1.9(lH, m), 1.9-1.65(5H, m), 0.98(3H, m); MS: 526.3(M+1). EXAMPLE 33 N-ri-(Benzooxazole-2-carbonyl)-propyll-2-cvclohexylmethyl-4-morpholin-4-yl-4-oxo- buiyramide (Compound 89) To a stirred mi ture of 2-cyclohexylmethyl-4-moφholin-4-yl-4-oxo-bu tyric acid (84.9mg, 0.3mmol), 2-amino-l-benzooxazol-2-yl-butan-l-ol TFA salt(96.9mg), prepared as in reference 21, and HOBt (55.1mg, 0.36mmol) in MeCl 2 (5ml), was added EDC (86.4mg, 0.45mmol) and N-methylmoφholine (0.25ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated ΝaHCO 3 , brine, dried with MgSO 4 and concentrated to yield 150 mg of N-[l-(benzooxazol-2-yl-hydroxy-mefhyl)-propyl]-2-cyclohexylmethyl-4- moφholin-4-yl-4-oxo-butyramide; MS: 470.5(M-1), 472.4(M+1). This amide was tteated with Dess-Martin periodinane (237.6mg, 0.48mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO 4 and concentrated. The residue was purified with silica gel column chromatography to yield 76 mg of N- [ " 1 - ( benzooxazole-2-carbonyl)- propyl1-2-cyclohexylmet_ιyl-4-moφholin-4-yl-4-oxo-butyramide; H 1 ΝMR(DMSO-d): 8.49(1H, d, J=5.2Hz, NH), 7.96(1H, d, J=7.6Hz), 7.86(1H, d, J=8.4), 7.6(1H, m), 7.5(1H, m), 5.14-5.04(1H, m), 3.6-3.25(8H, m), 2.9-2.75(lH, m), 2.5-2.4(lH, m), 2.25-2J5(lH, m), 2-1.8(lH, m), 1.8-1/7(2H, m), 1.7-1.6(1H, m), 1.6-1.4(5H, m), 1.35-1.2(1H, m), 1.2- 1(4 H, m), 0.96(3H, t); MS: 468.6(M-1), 470.5(M+1), 492.3(M+Na). EXAMPLE 34 2-Cyclohexylmethyl-4-moφholin-4-yl-N-ri-(oxazolor4,5-b1pyridine-2-carbonyl)- propyll -4-oxo-bu t yramide (Compound 90) To a stirred mixture of 2-cyclohexylmethyl-4-moφholin-4-yl-4-oxo-butyric acid (84.9mg, 0.3mmol), 2-amino-l-(5-phenyl-[l,3,4]oxadiazol-2-yl)-l-butanol TFA salt (97.5mg), prepared as in reference 21, and HOBt (55. Img, 0.36mmol) in MeCl 2 (5ml), was added EDC (86.4mg, 0.45mmol) andN-methylmoφholine (0.25ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated ΝaHCθ 3 , brine, dried with MgSO and concentrated to yield 153mg of 2-cyclohexylmethyl-N-[l-(hydroxy-oxazolo[4,5-b]pyridin- 2-yl-methyl)-propyl]-4-moφholm-4-yl-4-oxo-butyramide; MS: 471.6(M-1), 473.3(M+1). This amide was treated with Dess-Martin periodinane (237.6mg, 0.48mmol) at room temperature. After stkring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was extracted with ethyl acetate, washed with brine, dried with MgSO 4 and concenttated. The residue was purified with silica gel column chromatography to yield 95 mg of 2-cvclohexylmethyl-4-moφholin-4-yl- N-ri-(oxazolor4,5-b1pyridme-2-carbonylVpropyl1-4-oxo-butyramide: H 1 ΝMR(DMSO-d): 8.72-8.68(lH, m), 8.6(1H, d, J=5.2Hz, NH), 8.4-8.34QH, m), 7.68-7.59(lH, m), 5.2- .96(1H, m), 3.5-3.45(8H, m), 2.58(1H, m), 2.5-2.4(lH, m), 2.45-2.15(lH, m), 2.05- 1.9(lH, m), 1.85-1.65(2H, m), 1.6-1.4(5H,m), 1.3-1.2(lH,m), 1.25-l(4H,m),0.97(3H, t); MS: 469.6(M-1), 471.4(M+1), 493.2(M+Na). EXAMPLE 35 2-Cvclohexylmethyl-N-ri-(5-ethyl-ri,3,41oxadiazole-2-carbonyl)-butyl1-4-moφholin- 4-yl-4-oxo-butyramide (Compound 91) To a stirred mixture of 2-cyclohexylmethyl-4-moφholin-4-yl-4-oxo-butyric acid (84.9mg, 0.3mmol), 2-amino-l-(5-ethyl-l,3,4-oxadiazole-2-yl)-l-pentanol HCl salt (70.5mg), prepared as in reference 21, and HOBt (55. Img, 0.36mmol) inMeCl 2 (5ml), was added EDC (86.4mg, 0.45mmol) and N-methylmoφholine (0.25ml) at room temperature. After stirring for 14 hours, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated ΝaHCθ 3 , brine, dried with MgSO 4 and concenttated to yield 142 mg of 2-cyclohexylmethyl-N-{ l-[(5-ethyl-[ 1,3,4] oxadiazol-2-yl)- hydroxy-me fhyl] -butyl } -4-moφholin-4-yl-4-oxo-butyramide; MS : 463.5 (M- 1 ), 465.3(M+1). This amide was treated with Dess-Martin periodinane (239mg, 0.48mmol) at room temperature. After stirring for 1 hour, 5mls of saturated Νa 2 S 2 O 3 -ΝaHCO 3 were added. After a further 0.5 hours, the reaction mixture was extracted with ethyl acetate, washed with brine, dried with MgSO and concenttated. The residue was purified with silica gel column chromatography to yield 65 mg of 2-cyclohexylmethyl-N-ri-(5-ethyl- ri,3.41oxadiazole-2-carbonyl)-butyl1-4-moφholin-4-yl-4-oxo-butyramide; H 1 NMR (DMSO-d): 8.6, 8.51(1H, dd, J=6.8Hz, J=5.6Hz, NH, diastereomeric), 4.98(-4.88(lH, m), 3.6-3.25(8H, m), 3-2.9(2H, q, J=7.6Hz), 2.9-2.75(lH, m), 2.5-2.4(lH, m), 2.3-2.1(lH, m), 1.9-1.7(2H, m), 1.7-1.4(7H, m), 1.4-1.2(2H, m), 1.28(3H, t), 1.2-1(6H, m), 0.88(3H, t); MS: 461.4(M-1), 463.4(M+1), 485.4(M+Na). EXAMPLE 36 N-(2-Benzooxazol-2-yl-l-methoxymethyl-2-oxo-ethyl)-2-(2-difluoromethoxy- benzylsulfonylmethyl)-4-morpholin-4-yl-4-oxo-butyramide (Compound 92) To a stirred mixture of 2-(2-difluoromethoxy-benzylsulfonylmethyl)-4-moφhoUn- 4-yl-4-oxo-butyric acid (210.5mg, 0.5mmol), 2-amino-l-benzooxazol-2-yl-3-methoxy- propan-1-ol (112.5mg), and HOBt (91.8mg, 0.6mmol) in MeCl 2 (5ml), was added EDC (144mg, 0.75mmol) and Ν-methylmoφholine (0.35ml) at room temperature. After stirring for 14 hours, the reaction mixture was exttacted with ethyl acetate. The organic layer was washed with saturated ΝaHCO , brine, dried with MgSO 4 and concenttated to yield 301mg of N-(2-benzooxazol-2-yl-2-hydroxy-l-methoxymethyl-ethyl)-2-(2-difluoromethoxy- benzylsulfonylmethyl)-4-moφholin-4-yl-4-oxo-butyramide; MS: 624.5(M-1), 626.3(M+1). This amide(150mg, 0.24mmol) was treated with Dess-Martin periodinane (178mg, 0.36mmol) at room temperature. After stirring for 1 hour, 5ml of saturated Νa 2 S O 3 - NaHCO 3 were added. After a further 0.5 hours, the reaction mixture was exttacted with ethyl acetate, washed with brine, dried with MgSO and concenttated. The residue was purified with silica gel column chromatography to yield 39 mg ofN-(2-Benzooxazol-2-yl- l-methoxymemyl-2-oxo-e1_ιyl)-2-(2-difluoromethoxy-benzylsulfonylmethyl)-4-moφhohn- 4-yl-4-oxo-butyramide: H 1 NMR(DMSO-d): 8.97, 8.8(1H, dd, J=5.6Hz, J=5.6Hz, NH, diastereomeric), 8.02-7.94(lH, m), 7.9-7.84(lH, m), 7.66-7.58(lH, m), 7.55-7.38(3H, m), 7.3-7.18(2H, m), 7.1(1H, t, J=73.6Hz), 5.54-5.42(lH, m), 4.6-4.4(4H, m), 3.92-3.84(lH, m), 3.82-3.72(lH, m), 3.68-3.1(1 lH, m), 2.7-2.56(lH, m), 1.7-1.55(lH,m), 1.3-l(lH,m); MS: 622.4(M-1), 624.3(M+1), 646.3(M+Na). EXAMPLE 37 N-[l-(Benzooxazole-2-carbonyl)-propyl]-2-(2-cyclohexyl-ethyl)-4-moφholin-4-yl-4- oxo-butyramide (Compound 93) IH), 7.86 (d, J=8.2Hz, IH), 7.59 (t, J=8.2Hz, IH), 7.51 (t, J=8.2Hz, IH), 5.09-5.03 (m, IH), 3.56-3.27 (m, 8H), 2.72-2.64 (m, IH), 2.54-2.46 (m, IH), 2.21 (dd, J=15.8Hz, J=5.3Hz, IH), 1.99-1.89 (m, IH), 1.76-1.65 (m, IH), 1.60-0.95 (m, 13H), 0.96 (t, J=7Hz, 3H), 0.72-0.60 (m, 2H). MS: (M+H) + 484. , EXAMPLE 38 2-(2-Cvclohexyl-ethyl)-4-moφholin-4-yl-N-ri-(oxazolor4,5-b1pyridine-2-carbonyl)- propyll -4-oxo-butyr amide (Compound 94) Η NMR: (DMSO) 8.71-8.68 (m, IH), 8.58 (d, J=4.7Hz, IH), 8.36 (d, J=8.5Hz, IH), 7.66-7.61 (m, IH), 5.00-4.93 (m, IH), 3.56-3.26 (m, 8H), 2.72-2.63 (m, IH), 2.54- 2.44 (m, IH), 2.20 (dd, J=15.8Hz, J=5.3Hz, IH), 2.02-1.92 (m, IH), 1.78-1.67 (m, IH), 1.60-0.95 (m, 13H), 0.97 (t, J=7Hz, 3H), 0.68-0.57 (m, 2H). MS: (M+H) + 485. EXAMPLE 39 2-(2-Cyclohexyl-ethyl)-4-moφholin-4-yl-4-oxo-N-ri-(5-phenyl-ri,3,4]oxadiazole-2- carbonvD-propyll-butyramide (Compound 95) 1H ΝMR: (DMSO) 8.54 (d, J=4.7Hz, IH), 8.10-8.04 (m, 2H), 7.70-7.58 (m, 3H), 4.91-4.85 (m, IH), 3.55-3.22 (m, 8H), 2.70-2.62 (m, IH), 2.56-2.45 (m, IH), 2.22 (dd, J=15.5Hz, J=5Hz, IH), 1.98-1.88 (m, IH), 1.77-1.66 (m, IH), 1.60-0.95 (m, 13H),0.96(t, J=7Hz, 3H), 0.75-0.60 (m, 2H). MS: (M+H) + 511. EXAMPLE 40 2-(2-Difluoromethoxy-benzylsulfonylmethyl)-4-morpholin-4-yl-4-oxo-N-ri-(5-phenyl- ri,3,41oxadiazole-2-carbonyl)-proρyl1-butyramide (Compound 96) 1:1 Mixture of diastereomers. l H NMR: (DMSO), 8.89 (d, J=5.6Hz), 8.82 (d, J=6Hz) IH], 8.08-8.03 (m, 2H), 7.70-7.18 (m, 7H)„ 7.11 (t, JH,F=74Hz), 7.08 (t, JH,F=74Hz) IH], 5.01-4.90 (m, IH), 4.56-4.43 (m, 2H), 3.56-3.13 (m, 10H), 2.68-2.40 (m, 3H), 2.00-1.90 (m, IH), 1.78-1.68 (m, IH), 0.96 (t, J=7Hz, 3H). MS: (M+H) + 635. EXAMPLE 41 2-(2-Difluoromethoxy-benzylsulfonylmethyl)-N-ri-(5-ethyl-ri,3,41oxadiazole-2- carbonyl)-butyll-4-morpholin-4-yl-4-oxo-butyramide (Compound 97) 1:1 Mixture of diastereomers. J H ΝMR: (DMSO), 8.82 (d, J=5.5Hz), 8J7 (d, J=5Hz) IH], 7.51-7.42 (m, 2H), 7.30-7.19 (m, 2H)„ 7.11 (t, JH,F=74Hz), 7.10 (t, JH,F=74Hz) IH], 5.02-4.92 (m, IH), 4.56-4.43 (m, 2H), 3.58-3.26 (m, 10H), 3.20-3.12 (m, IH), 2.98-2.89 (m, 2H), 2.68-2.44 (m, 2H), 1.86-1.76 (m, IH), 1.69-1.58 (m, IH), 1.46- 1.20 (m, 5H), 0.88 (t, J=7Hz, 3H). MS: (M+H) + 601. EXAMPLE 42 N-ri-(Benzooxazole-2-carbonyl)-propyl]-2-(2-difluoromethoxy-benzyl- sulfonylmethyl)-4-moφholin-4-yl-4-oxo-butyramide (Compound 98) 1:1 Mixture of diastereomers. 1H ΝMR: (DMSO), 8.85 (d, J=5.3Hz), 8.76 (d, J=5.3Hz) 1H], 7.97 (t, J=6.5Hz, IH), 7.89-7.84 (m, IH), 7.64-7.18 (m, 6H)„ 712 (t, JH,F=74Hz), 7.10 (t, JH,F=74Hz) IH], 5.22-5.11 (m, IH), 4.56-4.42 (m, 2H), 3.58-3.12 (m, IIH), 2.67-2.42 (m, 2H), 2.02-1.92 (m, IH), 1.78-1.66 (m, IH), 0.96 (t, J=7Hz, 3H). MS: (M+H) + 608. EXAMPLE 43 2- ( 2-Morpholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, 1 -(benzooxazole-2- carbonvD-propyll -amide (Compound 99) 2-(2-Moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid (83.7 mg, 0.274 mmol), prepared as in reference 25, and HOBT (62.9 mg, 0.466 mmol) were added to a suspension of PS-bound N-Cyclohexylcarbodiimide (HL 200-400mesh cross linked with 2% DVB) from Novabiochem (322.3 mg, 0.548 mmol, 1.7 mmol/g loading) in methylene chloride (8 ml) and stirred at room temperature for 15 minutes. 2-Amino- l-benzooxazol-2-yl-butan-l- ol (56.5 mg.0.274 mmol), prepared as in reference 20, was added and the reaction mixture stirred overnight at room temperature. Silicycle ttisamine-3 (380.5 mg, 1.37 mmol, 3.6 mmol/g loading) was added and stirred for another 2 hours. The mixture was filtered and the filtrate evaporated under reduced pressure to give 2-(2-moφholin-4-yl-2-oxo-ethyl)-5- phenyl-pentanoic acid, l-(benzooxazol-2-yl-hydroxy-methyl)-propyl]-amide as a yellow solid (128 mg). To a solution of 2-(2-mθφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, 1- (benzooxazol-2-yl-hydroxy-methyl)-propyl]-amide (128 mg, 0.259 mmol) in methylene chloride (5 ml), Dess-Martin Periodinane (0.519 mmol, 220 mg) was added and stirred at room temperature for 90 minutes. The reaction mixture was washed with a solution of Na 2 S 2 O 3 in saturated NaHCO 3 , dried over MgSO 4 and concentrated under reduced pressure. The residue was purified by chromatography, eluting with a mixture of ethyl acetate and heptane, to give 2-(2-moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, 1- _benzooxazole-2-carbonyl)-propyπ-amide as a mixture of diastereoisomers (77 mg); X H NMR (CDC1 3 ) 7.90 (d, J=8Hz, IH), 7.65 (d, J=8.2Hz, IH), 7.55 (t, J=7.3Hz, IH), 7.46 (t, J=7.2Hz, IH), 7.4-7.1 (m, 5H)„ 7.0 (d, J=7.4Hz), 6.76 (d, J=7.1Hz), IH], 5.60 (m, IH), 3.8-3.4 (m, 8H), 3.1-2.5 (m, 4H), 2.4-2.1 (m, 2H), 2.0-1.6 (m, 4H), 1.5 (m, IH), 1.1 (m, 3H). MS : 492 (MH + ). EXAMPLE 44 (R)-2-Cyclohexylmethyl-4-moφholin-4-yl-4-oxo-N-r(S)-l-(5-phenyl-l,2,4-oxadiazole- 3-carbonyl)-propyl1-butyramide (Compound 100) Similarly prepared according to the general procedure given for Example 43 but using (R)-2-cyclohexylmethyl-4-moφholin-4-yl-4-oxo-butyric acid, prepared as described in reference 21, and (S)-2-amino-l-(5-phenyl-[l,2,4]oxadiazol-3-yl)-butan-l-ol, prepared as in reference 26; MS: 519 (M+Na), LC-MS retention time 4.5 min; 1H NMR (CDC1 3 ) 8.19 (d, J =7Hz, 2H), 7.65-7.51 (m.3H), 6.64 (d, J=7Hz, IH), 5.44-5.38 (m, IH), 3.69-3.38 (m, 8H), 3.05-2.98 (m, IH), 2.76 (dd, J=16Hz &10Hz, IH), 2.26 (dd, J=16Hz & 3Hz, IH), 2.10 (m, IH), 1.80 (m, IH), 1.75-1.59 (m, 6H), 1.28-1.13 (m, 5H), 1.03-0.98 (t, J = 7Hz, 3H), 0.92-0.81 (m, 2H). EXAMPLE 45 2-(2-Morpholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, (S)-l-(5-phenyl- ri,2,41oxadiazole-3-carbonyl)-propyl1-amide (Compound 101) Similarly prepared accordmg to the procedure for Example 43 but using 2-(2- moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid and (S)-2-amino-l-(5-phenyl- [l,2,4]oxadiazol-3-yl)-butan-l-ol; MS : 541 (M+Na), LCMS retention time 4.44 and 4.53 min; ΗNMR (CDC1 3 ) 8.18 (d, J= 7Hz, 2H), 7.69-7.51 (m, 3H), 7.27-7.10 (m, 5H), 6.99- 6.7 (d, J=7Hz, IH), 5.38 (m, IH), 3.70-3.36 (m, 8H), 2.99-2.56 (m, 4H), 2.27 (m, IH), 2.11 (m, IH), 1.87-1.60 (m, 4H), 1.44 (m, IH), 1.02-0.97(dt, J=7Hz, 3H). EXAMPLE 46 4-Moφholm-4-yl-4-oxo-2-benzylsulfonylmethyl-N-r(S)- 1 -(5-phenyl- 1 ,2,4-oxadiazole- 3-carbonyl)-propyl1-butyr amide (Compound 102) Similarly prepared according to the procedure for Example 43 but using 4-m oφholin-4-yl- 4-oxo-2-benzylsulfonylmethyl-butyric acid and (S)-2-amino-l-(5-phenyl-[l,2,4]oxadiazol- 3-yl)-butan-l-ol; MS: 569 (MH*), LCMS retention time 4.1 min; 1H ΝMR (CDC1 3 ) 8.18 (d, J= 7.9Hz, 2H), 7.74-7.31 (m, 9H), 5.27 (m, IH), 4.25 (m, 2H), 3.71-3.41 (m, 8H), 2.95 (m, IH), 2.78-2.70 (m, 2H), 2.10 (m, IH), 1.85 (m, IH), 1.0 (m, 3H). EXAMPLE 47 (R)-2-Cvclohexylmethyl-4-moφholm-4-yl-4-oxo-N- f ( S)- 1 -(3-phenyl- 1 ,2,4-oxadiazole- 5-carbonyl)-propyl1-butyramide (Compound 103) Similarly prepared according to the general procedure given for Example 43 above but using (R)-2-cyclohexylmethyl-4-moφholin-4-yl-4-oxo-butyric acid and (S)-2-amino-l- (3-phenyl-[l,2,4]oxadiazol-5-yl)-butan-l-ol; MS: 497 (MH + ). EXAMPLE 48 4-Moφholin-4-yl-N-ri-(oxazole-2-carbonyl)-3-phenyl-propyl1-4-oxo-2- benzylsulfonylmethyl-butyramide (Compound 104) Compound 104 was synthesized according to the following reaction protocol: Compound 1 (0.1066g, 0.3mmol) and compound 2 (0.0806g, 0.3mmol) were mixed with EDC (0.0633g,0.33mmol), HOBT (0.0446g, 0.33mmol) and DIEA (0.2ml, 1.2mmol) in 3 ml of DMF which was stirred at room temperature overnight. The reaction was diluted with ethyl acetate and washed with cold IN HCl, saturated sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified using a lOg silica gel column eluting with 10% ethyl acetate/n-heptane to 80% ethyl acetate/n-heptane to give 79.4 mg (46%) of product 3. Compound 3 (73mg, 0.13mmol) was then dissolved in 1 ml of methylene chloride and Dess-Martin periodinane (15% in methylene chloride, 0.7358 g) was added and the reaction was allowed to at room temperature for 3 hours and excess Dess-Martin reagent was consumed by adding sodium thiosulfate in saturated sodium bicarbonate. The product was exttacted with ethyl acetate and the organic layer was dried over magnesium sulfate, filtered and concenttated under reduced pressure. The product was purified using a lOg silica gel column eluting with 100% n-heptane to 30% n-heptane/ethyl acetate to yield 32.2 mg (44%) of the final compound 4; LCMS retention time 3:57 minutes, M+l(568.2). EXAMPLE 49 N-(l,l-Dimethyl-2-oxazol-2-yl-2-oxo-ethyl)-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide (Compound 105) Compound 105 was synthesized according to the following reaction protocol: Compound 1 (0.1066g, 0.3mmol) and compound 2 (0.0572g, 0.3mmol) were mixed with EDC (0.0633g,0.33mmol), HOBT (0.0446g, 0.33mmol) and DIEA (0.2ml, 1.2mmol) in 3 ml of DMF which was stirred at room temperature overnight. The reaction was diluted with ethyl acetate and washed with cold IN HCl, saturated sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified using a lOg silica gel column eluting with 10% ethyl acetate/n-heptane to 80% ethyl acetate/n-heptane to give 15 mg (10%) of final product 3; LCMS retention time 3:10 minutes, M+l(492.2). EXAMPLE 50 N-4-Isoρroρyl-N-l-ri-(oxazole-2-carbonv -3-ρhenyl-propyn-2-benzylsulfonylmethyl- succinamide (Compound 106) Compound 106 was synthesized accordmg to the following reaction protocol: To a stirring suspension of N-Cyclohexylcarbodiimide, N' -methyl polystyrene resin (1.7 mmole/gram, 0.3529g, 0.6 mmol) in 10ml of methylene chloride was added the acid 1 (98.2 mg, 0.3mmol) and HOBT (69mg, 0.5 lmmol) which was allowed to stir for 15 minutes at room temperature. Compound 2 (80.6 mg, 0.3mmol) and DIEA (0.1ml, 0.5mmol) were added and the reaction was allowed to stir for 5 hours at room temperature. Then silicycle triamine™ (0.42g, 1.5mmol) was added and the reaction was stirred overnight at room temperature. The reaction was filtered and the solvent was removed under reduced pressure. The crude product 3 was used without further purification. Crude compound 3 was dissolved in methylene chloride and Dess-Martin reagent (15% in methylene chloride, 1.13g, 0.6mmol) was added and the reaction was allowed to stir at room temperature for 3 hours. The excess Dess-Martin reagent was consumed by adding sodium thiosulfate in saturated sodium bicarbonate. The product was exttacted with ethyl acetate and washed with brine. The organic . layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The product was purified using HPLC to yield 15 mg of final compound 4; LCMS retention time 3:07 minutes, M+l(540.2). EXAMPLE 51 2-(2-Difluoromethoxy-benzylsulfonylmethyl)-4-moφholin-4-yl-N-ri-(oxazole-2- carbonyl)-3-phenyl-propyl1-4-oxo-butyramide (Compound 107) Compound 107 was synthesized according to the following reaction protocol: To a stirring suspension of N-Cyclohexylcarbodiimide, N-methyl polystyrene resin (1.7 mmole/gram, 0.2353g, 0.4 mmol) in 10ml of methylene chloride was added the acid 1 (84.3 mg, 0.2mmol) and HOBT (45.9mg, 0.34mmol) which was allowed to stir for 15 minutes at room temperature. Compound 2 (53.75 mg, 0.2mmol) and DIEA (0.068ml, 0.4 mmol) were added and the reaction as allowed to stir for 5 hours at room temperature. Then silicycle ttiamine™ (0.28g, l.Ommol) was added and the reaction was stirred overnight at room temperature. The reaction was filtered and the solvent was removed under reduced pressure. The crude product 3 was used without further purification. Crude compound 3 was dissolved in methylene chloride and Dess-Martin reagent (15% in methylene chloride, 1.13g, 0.6mmol) was added and the reaction was allowed to stir at room temperature for 3 hours. The excess Dess-Martin reagent was consumed by adding sodium thiosulfate in saturated sodium bicarbonate. The product was exttacted with ethyl acetate and washed with brine. The organic layer was dried over magnesium sulfate, filtered and concenttated under reduced pressure. The product was purified using HPLC to yield 6 mg of final compound 4; LCMS retention time 3:09 minutes, M+l(634.4). EXAMPLE 52 -(2-Me thyl-propane- 1 -sulfonylmethyl)-4-morpholin-4-yl-N-r 1 -(oxazole-2-carbonyl)-3- phenyl-propyll -4-oxo-butyramide (Compound 108) Compound 108 was synthesized according to the following reaction protocol: To a stirring suspension of N-Cyclohexylcarbodiimide, N-methyl polystyrene resin (1.7 mmole/gram, 0.2353g, 0.4 mmol) in 10ml of methylene chloride was added the acid 1 (64.3 mg, 0.2mmol) and HOBT (45.9mg, 0.34mmol) which was allowed to stir for 15 minutes at room temperature. Compound 2 (53.75 mg, 0.2mmol) and DIEA (0.068ml, 0.4 mmol) were added and the reaction was allowed to stir for 5 hours at room temperature. Then silicycle triamine™ (0.28g, l.Ommol) was added and the reaction was stirred overnight at room temperature. The reaction was filtered and the solvent was removed under reduced pressure. The crude product 3 was used without further purification. Crude compound 3 was dissolved in methylene chloride and Dess-Martin reagent (15% in methylene chloride, 1.13g, 0.6mmol) was added and the reaction was allowed to stir at room temperature for 3 hours. The excess Dess-Martin reagent was consumed by adding sodium thiosulfate in saturated sodium bicarbonate. The product was exttacted with ethyl acetate and washed with brine. The organic layer was dried over magnesium sulfate, filtered and concenttated under reduced pressure. The product was purified using HPLC to yield 25.7 mg of final compound 4; LCMS retention time 2:89 minutes, M+l (534.4). EXAMPLE 53 2-Cvclopropylmethylsulf onylmethyl-4-moφholin-4-yl-N- r 1 -(oxazole-2-carbonyl)-3- phenyl-propyll -4-oxo-bu tyramide (Compound 109) Compound 109 was synthesized according to the following reaction protocol: To a stirring suspension of N-Cyclohexylcarbodiimide, V -methyl polystyrene resin (1.7 mmole/gram, 0.2353g, 0.4 mmol) in 10ml of methylene chloride was added the acid 1 (63.9 mg, 0.2mmol) and HOBT (45.9mg, 0.34mmol) which was allowed to stir for 15 minutes at room temperature. Compound 2 (53.75 mg, 0.2mmol) and DIEA (0.068ml, 0.4 mmol) were added and the reaction was allowed to stir for 5 hours at room temperature. Then silicycle triamine™ (0.28g, l.Ommol) was added and the reaction was stirred overnight at room temperature. The reaction was filtered and the solvent was removed under reduced pressure. The crude product 3 was used without further purification. Crude compound 3 was dissolved in methylene chloride and Dess-Martin reagent (15% in methylene chloride, 1.13g, 0.6mmol) was added and the reaction was allowed to stir at room temperature for 3 hours. The excess Dess-Martin reagent was consumed by adding sodium thiosulfate in saturated sodium bicarbonate. The product was exttacted with ethyl acetate and washed with brine. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The product was purified using HPLC to yield 11.6 mg of final compound 4; LCMS retention time 2:77 minutes, M+l (532.4). EXAMPLE 54 N-ri-(Benzooxazole-2-carbonyl)-butyl1-2-benzylsulfonyl-3-(tettahydro-pyran-4- yloxymethvD-propionamide (Compound 110) Diisopropylethylamme (0.184 ml, 1.05 mmol) was added to a mixture of 3- benzylsulfonyl-2-(tettahydro-pyran-4-yloxymethyl)-propionic acid (362 mg, 1.05 mmol), prepared as in reference 27, and 2-amino-l-benzooxazol-2-yl-pentan-l-ol (238 mg, 1.05 mmol) and HATU (402 mg, 1.05 mmol) in DMF (10 ml) and stirred at room temperature overnight. Solvent was evaporated under reduced pressure, crude extract was taken up in ethyl acetate (30 ml) and washed with IN HCl, saturated ΝaHCO 3 and brine. After drying over MgSO the solvent was removed by rotary evaporation and the residue chromatographed on silica eluting with ethyl acetate/heptane mixture to give N-[(S)-1- (benzoxazol-2-yl-hydroxy-methyl)-butyl]-2-benzylsulfonylmethyl-3-(tettahydro-pyran-4- yloxy)-propionamide (Yield: 258 mg); MS: 545 (M+l); LCMS retention time 3.71 and 3.76 minutes. A solution of N-[(S)-l-(benzoxazol-2-yl-hydroxy-methyl)-butyl]-2- benzylsulfonylmethyl-3-(tettahydro-pyran-4-yloxy)-propionamide (243 mg, 0.45 mmol) methylene chloride (8 ml) was tteated with Dess-Martin periodinane (190 mg, 0.45 mmol) at room temperature for 2 hours. Washed with 0.26M solution of Νa 2 S 2 O 3 , NaHCO 3 and brine. After drying over MgSO the solvent was removed by rotary evaporation and the residue chromatographed on silica eluting with ethyl acetate/heptane mixture to give N-fl- (benzooxazole-2-carbonyl)-butyl1-2-benzylsulfonyl-3-(tettahvdro-pyran-4-yloxymethyl)- propionamide as off white solid (Yield: 60 mg); MS : 543 (M+l); LCMS retention time 4.1 minutes. EXAMPLE 55 N-ri-(Benzooxazole-2-carbonyl)-butyl1-3-ethanesulfonyl-2-(tettahydro-pyran-4- yloxymethvD-propionamide (Compound 111) By following the method for Example 54 but substituting the required carboxylic acid with 3-ethylsulfonyl-2-(tettahydro-pyran-4-yloxymethyl)-propionic acid, as prepared in reference 27b, N-ri-(benzooxazole-2-carbonyl)-butyl1-3-ethanesulfonyl-2-(tettahvdro- pyran-4-yloxymethyl)-propionamide was prepared. MS: 481 (M+l); LCMS retention time 3.7 minutes. EXAMPLE 56 N-(l-Benzenesulfonyl-3-oxo-azepan-4-yl)-2-cvclopropylmethylsulfonylmethyl-4- morpholin-4-yl-4-oxo-butyramide (Compound 112) Compound 112 was prepared by the following protocol. The circle symbolizes the polystyrene backbone while the square symbolizes the silicium dioxide backbone: 1.16 mol-equivalents of the acid were dissolved in dichloromethyl. N- Cyclohexylcarbodiimide, N-methylpolystyrene (2 mol-equivalents) and hydroxybenzotriazole (1.72 mol-equivalents) were added and the resulting reaction mixture stirred for 10 minutes. 4-Amino-3-hydroxy-azepane-l-carboxylic acid tert-butyl ester (1 mol-equivalent) was added and stirring continued for 21 hours. Silicycle-Triamine-3™ was added and the resulting mixture stirred for six hours. The mixture was filtered under suction and the filtrate concenttated under vacuum. The alcohol was dissolved in dichloromethyl and 2 mol-equivalents of Dess-Martin periodinane were added to the solution. The reaction mixture was stirred for one hour. Equal volumes of saturated sodium thiosulfate solution and sat sodium bicarbonate solution were added and the phases separated. The aqueous phase was exttacted three times with dichloromethyl. The combined organic phases were washed with saturated sodium bicarbonate solution and saturated sodium chloride solution. The solution was dried with magnesium sulfate and the solvents evaporated. The azepanone-1 -carboxylic acid tert-butyl ester was dissolved in a dichloromethyl solution (20vol-%) of trifluoroacetic acid. After stirring for one hour dichloromethyl was removed under reduced pressure and trifluoroacetic acid under high vacuum. The solid residue was re-dissolved in dichloromethyl and five mol-equivalent of triethylamine were added. 1.2 mol-equivalent of benzenesulfonyl chloride were added and the reaction mixture stirred for four hours. 12 mol-equivalents of Silicycle Triamine™ were added and stirring continued for two hours. The mixture was filtered under suction and the dichloromethyl evaporated under reduced pressure. The crude product was purified via preparative HPLC yielding N-(l-benzenesulfonyl-3-oxo-azepan-4-yl)-2-cvcloproρylmethylsulfonylmethyl-4- moφholin-4-yl-4-oxo-butyramide as an off-white solid; LC/MS retention time 2.61 minutes, mJz=570 (M+H). The following examples were prepared according to methods described in Example 56: 2-Cvclopropylmethylsulfonylmethyl-Ν-{(S)-l-F(R)-hvdroxy-(3-phenyl-l,2,4-oxadiazol- 5-yl)-methyl1-propyl ,-4-moφholm-4-yl-4-oxo-butyr amide (Compound 122) Tan solid; LC MS retention time 3.456 minutes (TIC), m/z=557 (M+Na). N-((S)-l-r(R)-hydroxy-(3-phenyl-l,2,4-oxadiazol-5-yl)-methvn-propyl}-2-(2-methyl- propane- 1 -sulf onylmethyl)-4-moφholm-4-yl-4-oxo-butyramide (Compound 123) Tan solid; LC/MS retention time 3.594 minutes (TIC), m/z=559 (M+Νa). 2-(2-Moφholm-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid { (S)-l-r (R)-hvdroxy-(3- phenyl- 1 ,2,4-oxadiazol-5-yl)-me fhvH -propyl ) -amide (Compound 124) Tan solid; LC/MS retention time 3.379 minutes (TIC), m z=521 (M+H). -Cvclopropylmethylsulfonylmethyl-4-moφholin-4-yl-4-oxo-N-r.S)-l-(3-phenyl-l,2,4- oxadiazole-5 -carbonvD-propyll -butyramide (Compound 125) Tan solid; LC/MS retention time 2.976 minutes (TIC), m/z=533 (M+H). -(2-methyl-propane-l-sulfonylmethyl)-4-moφholin-4-vI-4-oxo-N-r(S)-l-(3-phenyl- l,2,4-oxadiazole-5-carbonyl)-propyl1-butyramide (Compound 126) Tan solid; LC/MS retention time 3.433 minutes (TIC), m/z=535 (M+H). 2-(2-Morpholin-4-yl-2-oxo-e thyl)-5 -phenyl-pentanoic acid, (S)- 1 -(3 -phenyl- 1 ,2,4- oxadiazole-5-carbonyl)-propyl , -amide (Compound 127) Tan solid; LC/MS retention time 3.762 minutes (TIC), m/z=519 (M+H). EXAMPLE 57 3-Hvdroxy-4-(4-moφholin-4-yl-4-oxo-2-benzylsmfonylmethyl-butyrylamino)-azepane- 1 -carboxylic acid tert-butyl ester (Compound 113) Tan solid prepared according to example 56; LC/MS retention time 2.985 minutes (TIC), m z=568 (M+H) and 590 (M+Na). EXAMPLE 58 4-(2-Cvcloproρylmethylsulfonylmemyl-4-morpholm-4-yl-4-oxo-butyrylamino)-3- hydroxy-azepane-1 -carboxylic acid tert-butyl ester (Compound 114) Tan solid prepared according example 56; LC/MS retention time 2.786 minutes (TIC), m/z=532 (M+H) and 554 (M+Na). EXAMPLE 59 3-Hvdroxy-4-r2-(2-methyl-propane-l-sulfonylmethyl)-4-moφholin-4-yl-4-oxo- butyrylaminol-azepane-l -carboxylic acid tert-butyl ester (Compound 115) Tan solid prepared according example 56; LC/MS retention time 2.903 minutes (TIC), m z=534 (M+H). EXAMPLE 60 4-(4-Morpholin-4-yl-4Hθxo-2-benzylsulfonylmeι yl-buiyrylamino)-3-oxo-azepane-l- carboxylic acid tert-butyl ester (Compound 116) Tan solid prepared accordmg example 56; LC/MS retention time 3.163 minutes (TIC), m/z=566 (M+H). EXAMPLE 61 4-(2-Cvclopropylmethylsulfonylmethyl-4-moφholin-4-yl-4-oxo-butyrylamino)-3-oxo- azepane-1 -carboxylic acid tert-butyl ester (Compound 117) Tan solid prepared according to example 56; LC/MS retention time 2.965 minutes (TIC), m/z=530 (M+H). EXAMPLE 62 4-r2-(2-Methyl-propane-l-sulfonylmethyl)-4-moφholin-4-yl-4-oxo-butyrylarnino1-3- oxo-azepane-1 -carboxylic acid tert-butyl ester (Compound 118) Tan solid prepared according to example 56; LC/MS retention time 3.083 minutes (TIC), m/z=532 (M+H). EXAMPLE 63 N-(l-Benzenesulfonyl-3-oxo-azepan-4-yl)-4-moφholm-4-yl-4-oxo-2- benzylsulfonylmethyl-butyramide (Compound 119) Off-white solid prepared according example 56; LC/MS retention time 2.83 minutes (TIC), m/z=606 (M+H). EXAMPLE 64 N-(l-Benzenesulfonyl-3-oxo-azepan-4-yl)-2-(2-methyl-proρane-l- sulfonylmethyl)-4-moφholin-4-yl-4-oxo-butyramide (Compound 120) Off-white solid prepared accordmg example 56; LC/MS retention time 2.72 minutes (TIC), m/z=572 (M+H). EXAMPLE 65 N-r(lS)-l-(Benzooxazol-2-yl-hvdroxy-methyl)-3-phenyl-propyll-2- cvclopropylmethylsulfonylmethyl-4-moφholin-4-yl-4-oxo-butyramide (Compound 121) Compound 121 was prepared according to the following reaction scheme: 3. Silicycle Triamine-3 (basic silica gel scavenger) 0.25mmol (1J6 mol-equivalent) of 2-cyclopropylmethylsulfonylmethyl-4- moφholin-4-yl-4-oxo-butyric acid was dissolved in 10ml dichloromethyl. 252mg, 0.43mmol N-cyclohexylcarbodiimide, N-methylpolystyrene (2 mol-equivalents) and 50mg, 0.37mmol hydroxybenzottiazole (1.72 mol-equivalents) were added and the resulting reaction mixture stirred for 10 minutes. 61mg, 0.215mmol 2-amino-l- benzooxazol-2-yl-4-phenyl-butan-l-ol (1 mol-equivalents) was added and stirring continued for 21 hours. 510mg, 2.15mmol Silicycle-Triamine-3™ was added and the resulting mixture stirred for 6 hours. The mixture was filtered under suction and the filtrate concenttated under vacuum yielding 83mg, 0.142mmol (66%) ofN-r(lS)-l-(Benzooxazol- 2-yl-hvdroxy-methyl)-3-phenyl-propyn-2-cvclopropylmethylsulfonyl-0methyl-4- morpholm-4-yl-4-oxo-butyramide as a tan solid; LC/MS retention time 3.256min (TIC), m/z=584 (M+H). EXAMPLE 66 (R)-2-((S)- 1 -Hvdroxy-2-moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, 1 - (benzoxazole-2-carbonyl)-propyl1-amide (Compound 128) PyBOP (126 mg, 0.24 mmol), DIPEA (0.096 ml, 0.55mmol) and 2-Amino-l- benzooxazol-2-yl-butan-l-one hydrochloride (53 mg, 0.22 mmol) were added to a solution of (R)-2-((S)-l-Hydroxy-2-moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid (70.7 mg, 0.22 mmol) in dry methylene chloride (5 ml) and the reaction mixture was stirred overnight at room temperature. The reaction was concenttated under reduced pressure, the residue dissolved in ethyl acetate and washed with water. Organic extract was dried over MgSO and evaporated under reduced pressure. Column chromatography on silica eluting with a mixture of ethyl acetate and heptane gave the title compound as white solid (38 mg); H NMR (CDCI 3 ) δ 1.02 (t, J=7.4Hz, 3H), 1.97-1.62 (m, 5H), 2.21-2.15 (m, IH), 2.74-2.59 ( , 3H), 3.65-3.49 (m, 8H), 4.41 (m, IH), 4.70 ( , IH), 5.62 (m, IH), 6.93 (d, J=7.1Hz) 6.68 (d, J=7.1Hz, IH), 7.33-7.13 (m, 5H), 7.49 (t, J=8Hz, IH), 7.57 (t, J=8Hz, IH), 7.66 (d, J=5.9, IH), 7.92 (d, J=8Hz, IH); MS: 508(MH + ); LC/MS retention time was 3.05 minutes. EXAMPLE 67 (R)-5-(2-Difluoromethoxy-phenyl)-2-((S)-l-hydroxy-2-moφholin-4-yl-2-oxo-ethyl)- pentanoic acid, l-(benzoxazole-2-carbonyl)-propyl1 -amide (Compound 129) Similarly prepared according to the procedure in Example 66 but using (R)-5-(2- difluoromethoxy-phenyl)-2-((S)-l-hydroxy-2-moφholin-4-yl-2-oxo-ethyl)-pentanoic acid as the acidic component; *H NMR (CDC1 3 ) δ 1.06 (t, J=7.5Hz, 3H), 1.97-1.63 (m, 5H), 2.23-2.14 (m, IH), 2.79-2.68 (m, 3H), 3.75-3.50 (m, 8H), 4.42 (m, IH), 4.81-4.62 (m, IH), 5.61 (m, IH), 6.53 (t, J=74Hz, IH), 6.73 (d, J=7.1Hz), 6.98 (d, J=7.1Hz, IH), 7.24-7.06 (m, 4H), 7.59-7.49 (m, 2H), 7.69-7.64 (m, IH), 7.91 (d, J=7.9Hz, IH); MS: 574(MH + ). EXAMPLE 68 4-Morpholm-4-yl-N-ri-(oxazole-2-carbonyl)-cvclopropyl1-4-oxo-2-benzylsulfonyl methyl -butyramide (Compound 130) Similarly prepared according to the procedure in Example 66 but using 4- moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid as the acidic component and (1- Amino-cyclopropyl)-oxazol-2-yl-methanone hydrochloride as the basic component; MS: 490 (MH 1 ); LC/MS, retention time 2.44 minutes. EXAMPLE 69 Cathepsin S Assay Solutions of test compounds in varying concentrations were prepared in 10 μL of dimethyl sulfoxide (DMSO) and then diluted into assay buffer (40 μL, comprising: MES, 50 mM (pH 6.5); EDTA, 2.5 mM; and NaCl, 100 mM). Human cathepsin S (0.158 pMoles in 25 μL of assay buffer) was added to the dilutions. The assay solutions were mixed for 5- 10 seconds on a shaker plate, covered and incubated for 30 minutes at ambient temperature. Z-Val-Val-Arg-AMC (9 nMoles in 25 μL of assay buffer) was added to the assay solutions and hydrolysis was followed specttophotometrically at (λ 460 nm) for 5 minutes. Apparent inhibition constants (KO were calculated from the enzyme progress curves using standard mathematical models. EXAMPLE 70 Cathepsin B Assay Solutions of test compounds in varying concentrations were prepared in 10 μL of dimethyl sulfoxide (DMSO) and then diluted into assay buffer (40 μL, comprising: N,N- bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), 50 mM (pH 6); polyoxyethylenesorbitan monolaurate, 0.05%; and dithiothreitol (DTT), 2.5 mM). Human cathepsin B (0.025 pMoles in 25 μL of assay buffer) was added to the dilutions. The assay solutions were mixed for 5-10 seconds on a shaker plate, covered and incubated for 30 minutes at ambient temperature. Z-FR-AMC (20 nMoles in 25 μL of assay buffer) was added to the assay solutions and hydrolysis was followed specttophotometrically at (λ 460 nm) for 5 minutes. Apparent inhibition constants (KO were calculated from the enzyme progress curves using standard mathematical models. EXAMPLE 71 Cathepsin K Assay Solutions of test compounds in varying concentrations were prepared in 10 μL of dimethyl sulfoxide (DMSO) and then diluted into assay buffer (40 μL, comprising: MES, 50 mM (pH 5.5); EDTA, 2.5 mM; and DTT, 2.5 mM). Human cathepsin K (0.0906 pMoles in 25 μL of assay buffer) was added to the dilutions. The assay solutions were mixed for 5-10 seconds on a shaker plate, covered and incubated for 30 minutes at ambient temperature. Z-Phe-Arg-AMC (4 nMoles in 25 μL of assay buffer) was added to the assay solutions and hydrolysis was followed specttophotometrically at (λ 460 nm) for 5 minutes. Apparent inhibition constants (KO were calculated from the enzyme progress curves using standard mathematical models. EXAMPLE 72 Cathepsin L Assay Solutions of test compounds in varying concentrations were prepared in 10 μL of dimethyl sulfoxide (DMSO) and then diluted into assay buffer (40 μL, comprising: MES, 50 mM (pH 5.5); EDTA, 2.5 mM; and DTT, 2.5 mM). Human cathepsin L (0.05 pMoles in 25 μL of assay buffer) was added to the dilutions. The assay solutions were mixed for 5- 10 seconds on a shaker plate, covered and incubated for 30 minutes at ambient temperature. Z-Phe-Arg-AMC (1 nMoles in 25 μL of assay buffer) was added to the assay solutions and hydrolysis was followed specttophotometrically at (λ 460 nm) for 5 minutes. Apparent inhibition constants (Kj) were calculated from the enzyme progress curves using standard mathematical models. Compounds of the invention were tested according to the above-described assays for protease inhibition and observed to exhibit selective cathepsin S inhibitory activity. For example, the compounds of the invention were found to inhibit cathepsin S protease activity at concentrations that are least 50 fold less than those concentrations required to produce an equiactive inhibition of cathepsin K protease activity. The apparent inhibition constants (KO for compounds of the invention, against Cathepsin S, were in the range from about 10 ~10 M to about 10 "7 M. EXAMPLE 73 Representative Pharmaceutical Formulations Containing a Compound of Formula I ORAL FORMULATION Compound of Formula I 10- 100 mg Citric Acid Monohydrate 105 mg Sodium Hydroxide 18 mg Flavoring Water q.s. to 100 mL INTRAVENOUS FORMULATION Compound of Formula I 0J - 10 mg Dextrose Monohydrate q.s. to make isotonic Cittic Acid Monohydrate 1.05 mg Sodium Hydroxide 0.18 mg Water for Injection q.s. to 1.0 mL TABLET FORMULATION Compound of Formula I 1 % Microcrystalline Cellulose 73% Stearic Acid 25% Colloidal Silica 1%.

Claims: WE CLA : 1. A compound of Formula I: in which: . X 1 is -C(R X )(R 2 )X 2 or -X 3 ; X 2 is cyano, -CHO, -C(R 7 )(R 8 )R 5 , -C(R 7 )(R 8 )CF 3 , -C(R 7 )(R 8 )CF 2 CF 2 R 9 -CH=CHS(O) 2 R 5 , -C(R 7 )(R 8 )CF 2 C(O)NR 5 R 6 , -C(R 7 )(R 8 )C(R 7 )(R 8 )NR 5 R 6 , -C(R 7 )(R 8 )C(R 7 )(R 8 )OR 5 , -C(R 7 )(R 8 )CH 2 OR s , -C(R 7 )(R 8 )CH 2 N(R 6 )SO 2 R 5 , -C(R 7 )(R 8 )C(R 7 )(R 8 )N(R 6 )(CH 2 ) 2 OR 6 , -C(R 7 )(R 8 )C(R 7 )(R 8 )N(R 6 )(CH 2 ) 2 NR 6 or -C(R 7 )(R 8 )C(R 7 )(R 8 )R 5 ; wherein R 5 is (Cι. 4 )alkyl, (C 6 .ιo)aryl(Co- 6 )alkyl, hetero(C .ιo)aryl(C 0 - 6 )alkyl, (C 4 .ιo)cycloalkyl(C 0 . 6 )alkyl or hetero(C -ιo)cycloalkyl(C 0 - 6 )alkyl; R 6 is hydrogen or (Cι- 6 )alkyl; R 7 is hydrogen or (Cι. )alkyl and R 8 is hydroxy or R 7 and R 8 together form oxo; R 9 is hydrogen, halo, (Cι. 4 )alkyl, (C 5 -ιo)aryl(Co- 6 )alkyl or hetero(C 5 .ιo)aryl(C 0 - 6 )alkyl; X 3 represents a group of Formula (a): (a) in which n is 1 or 2, z is 0 or 1, X 5 is selected from NR 10 , S or O, wherem R 10 is hydrogen or (Cι- 6 )alkyl, and X 6 is O, S or NR 11 , wherein R 11 is selected from hydrogen, (Cι. 6 )alkyl, -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR I2 R 12 , -X 4 S(O) 2 R 14 , -R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 C(O)NR 12 R 15 and -X 4 S(O) 2 NR 12 R 15 , in which X 4 is a bond or (Cι_ 6 )alkylene; R 12 at each occurrence independently is hydrogen or (Cι. 6 )alkyl; R 13 is hydrogen, (Cι. 6 )alkyl or halo-substituted(Cι_g)alkyl, R 14 is (Cι_ 6 )alkyl or halo-subst_-Uted(Ci_ 6 )alkyl and R 15 is (C 3 .ιo)cycloalkyl(C 0 - 6 )alkyl, hetero(C 3 .io)cycloalkyl(C 0 . 3 )alkyl, (C 6 . 1 o)aryl(C 0 . 6 )alkyl, hetero(C 5 .ιo)aryl(Co- 6 )alkyl, (C 9 .ι 2 )bicycloaryl(Crj- 6 )alkyl or hetero(C 8 -ι 2 )bicycloaryl(Co- 6 )alkyl; wherein within X 1 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical R 20 selected from -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR ls R 12 , -X S(O) 2 NR 15 R 12 , -X 4 NR 12 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 ; and wherein X 1 and R 20 may be substituted further with 1 to 5 radicals independently selected from ( -^alkyl, cyano, halo, halo-substituted(C 1 . 4 )alkyl, nitro, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 wherem X 4 , R 12 , R 13 , R 14 and R 15 are as defined above; R 1 and R 2 are both fluoro; or R 1 is hydrogen or (Cι- 6 )alkyl and R 2 is selected from the group consisting of hydrogen, (Cι. 6 )alkyl, cyano, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 1 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 , -X 4 S(O) 2 R 14 , -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR 15 R 12 , -X 4 S(0) 2 NR 15 R 12 , -X 4 NR 12 S(0) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 , wherein X 4 , R 12 , R 13 , R 14 and R 15 are as defined above; or R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkyIene or hetero(C 3 . 8 )cycloalkylene; wherein R 2 , said cycloalkylene and said heterocycloalkylene may be substituted further with 1 to 3 radicals independently selected from (Cι. 6 )alkyl, cyano, halo, halo-substituted(C M )alkyl, nitto, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 , wherein X 4 , R 12 , R 13 and R 14 are as defined above; R 3 and R 4 are independently -C(R 16 )(R 17 )X 7 , wherein R 16 and R 17 are hydrogen, (Cι. 6 )alkyl or fluoro, or R 16 is hydrogen and R 17 is hydroxy and X 7 is selected from -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(p)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 , -X 4 S(O) 2 R 14 , -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR 15 R 12 , -X 4 S(O) 2 NR 15 R 12 , -X 4 NR 12 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 , wherein X 4 , R 12 , R 13 , R 14 and R 15 are as defined above; wherein within one of R 3 or R 4 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical R 21 selected from -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR 12 R 15 , -X 4 S(O) 2 NR 15 R 12 , -X 4 NR 12 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 , wherein X 4 , R 12 and R 15 are as defined above; and wherein each of R 3 , R 4 and R 21 may be substituted further with 1 to 5 radicals independently selected from (C 1 . 6 )alkyl, cyano, halo, halo-substituted(Cι_ )alkyl, nitro, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(0)(OR 12 )OR 12 , -X 4 OP(O)(OR 1 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 , wherem X 4 , R 12 , R 13 and R 14 are as defined above; provided that only one bicyclic ring structure is present within each of R 3 or R 4 ; and provided that when X 2 is cyano and X 7 within one of R 3 or R 4 is -X 4 C(O)R 13 or -X 4 C(O)R 15 , wherein X 4 is a bond, then X 7 within the other of R 3 or R 4 is limited to -X 4 SR 15 , -X 4 S(O)R 15 and -X 4 S(O) 2 R 15 , wherein R 15 is (C 6 . 10 )aryl(C 1 . 6 )alkyl substituted with 1 to 5 radicals or hetero(C s .ιo)aryl(Co- 6 )alkyl optionally substituted with 1 to 5 radicals, wherein said radicals are independently selected from (Chalky., cyano, halo, halo-substituted(Ci. 4 )alkyl, nitro, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 , wherein X 4 , R 12 , R 13 and R 14 are as defined above, provided that the radical is not selected from only halo when R 15 is (C 6 _i 0 )aryl(Ci-s)alkyl; and provided that when X 2 is cyano then X 7 within R 3 and R 4 is not -X 4 C(O)NR 12 R 12 , -X 4 C(O)NR 15 R 12 or -X 4 C(O)NR 18 R 19 , wherein X 4 is a bond and R 18 and R 19 together with the nitrogen atom to which they are attached form hetero(C 3 _ιo)cycloalkyl or hetero(C 5 -ι 0 )aryl; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 2. The compound of Claim 1 in which: X 1 is -C(R 1 )(R 2 )X 2 or -X 3 ; X 2 is cyano, -CHO, -C(O)R 5 , -C(O)CF 3 , -C(O)CF 2 CF 2 R 9 -CH=CHS(O) 2 R 5 , -C(O)CF 2 C(O)ΝR 5 R 6 , -C(O)C(O)NR 5 R 6 , -C(O)C(O)OR 5 , -C(O)CH 2 OR 5 , -C(O)CH 2 N(R 6 )SO 2 R 5 , -C(O)C(O)N(R 6 )(CH 2 ) 2 OR 6 , -C(O)C(O)N(R 6 )(CH 2 ) 2 NR 6 or -C(O)C(O)R 5 , wherein R 5 is (Cι. 4 )alkyl, (C 6 -ιo)aryl(C 0 . 6 )alkyl, hetero(C 4 .ιo)aryl(C 0 - 6 )alkyl, (C 4 _io)cycloalkyl(C 0 - 6 )alkyl or hetero(C .ι 0 )cycloalkyl(C 0 - 6 )alkyl, R 6 is hydrogen or (C 1 . 6 )alkyl and R 9 is halo; X 3 represents a group of Formula (b): (b) in which n is 1 or 2, z is 0 or 1, X 6 is O or NR 11 , wherein R 11 is selected from hydrogen, (Cι. 6 )alkyl, -X 4 OC(O)R 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 S(O) 2 R 14 , -R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 C(O)NR 12 R 15 and -X 4 S(O) 2 NR 12 R 15 , in which X 4 is a bond or (Cι. 6 )alkylene; R 12 at each occurrence independently is hydrogen or (C 1 . 6 )alkyl; R 13 is hydrogen, (Cι_ 6 )alkyl or halo-substituted(C 1 . 6 )alkyl, R 14 is (Cι_s)alkyl or halo-substituted(C 1 . 6 )alkyl and R 15 is (C 3 -ιn)cycloalkyl(C 0 .6)alkyl, hetero(C 3 . 10 )cycloalkyl(Co- 3 )alkyl, (C 6 .ιo)aryl(C 0 -6)alkyl, hetero(C 5 -i 0 )aryl(Co- 6 )alkyl, (C 9 . 12 )bicycloaryl(C 0 - 6 )alkyl or hetero(C 8 .ι 2 )bicycloaryl(Co- 6 )alkyl; wherein within X 1 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical selected from -R 15 and -X 4 C(O)R 15 ; and wherein X 1 may be substituted further with 1 to 3 radicals independently selected from (Cι__)alkyl, halo-substituted(C 1 . 4 )alkyl, -X 4 NR 12 R 12 , -X 4 OR 13 and -X 4 S(O) 2 R 14 , wherein X 4 , R 12 , R 13 , R 14 and R 15 are as defined above; R 1 and R 2 are both fluoro; or R 1 is hydrogen or (Cι- 6 )alkyl and R 2 is selected from the group consisting of hydrogen, (Cι. 6 )alkyl, -X 4 OR 13 and -R 15 ; or R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene or hetero(C 3 _ 8 )cycloalkylene; wherein R 2 may be substituted further with (Cι-g)alkyl; wherein X 4 , R 13 and R 15 are as defined above; R 3 and R 4 are independently -C(R 16 )(R 17 )X 7 , wherein R 16 and R 17 are hydrogen, (Cι_ 6 )alkyl or fluoro, or R 16 is hydrogen and R 17 is hydroxy and X 7 is selected from -X 4 SR 13 , -X 4 C(O)R 13 , -X C(O)NR 12 R 12 , -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 and -X 4 C(O)NR 15 R 12 , wherem X 4 , R 12 , R 13 and R 15 are as defined above; wherein within one of R 3 or R 4 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical selected from -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR 12 R 15 , -X 4 S(O) 2 NR I5 R 12 , -X 4 NR I2 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 , wherein X 4 , R 12 and R 15 are as defined above; and wherein each of R 3 and R 4 may be substituted further with 1 to 5 radicals independently selected from (Cι_ 6 )alkyl, cyano, halo, halo-substituted(Ci_ )alkyl, nitro, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 , wherein X 4 , R 12 , R 13 and R 14 are as defined above; wherein within one of R 3 and R 4 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical selected from -R 15 and -X 4 OR 15 ; and wherein each of R 3 or R 4 may be substituted further by 1-5 radicals independently selected from (Cι^)aUcyl, cyano, halo, halo-substituted(Cι. 4 )alkyl, -X 4 NR 12 C(O)OR 12 , -X 4 OR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 and -X 4 S(O) 2 R 14 , wherein X 4 , R 12 , R 13 , R 14 and R 15 are as defined above; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 3. A compound of claim 2 in which R 3 and R 4 are independently -CH 2 X 7 , wherein X 7 is selected from X 4 SR 13 , -X 4 C(O)R 13 , -X 4 C(O)ΝR 12 R 12 , -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 and -X 4 C(O)NR 15 R 12 , wherein X 4 is a bond or (Cι_ 6 )alkylene, R 12 at each occurrence independently is hydrogen or (Ci-s)alkyl, R 13 is hydrogen, (Cι_ 6 )alkyl or halo-substituted(Cι_ 6 )alkyl, R 14 is (Cι_ 6 )alkyl or halo-substituted(Ci_ 6 )alkyl and R 15 is (C 3 .ιo)cycloalkyl(C 0 - 6 )alkyl, (C 3 -ιo)cycloalkyl(Co. 6 )alkyl, hetero(C 3 -ιo)cycloalkyl(Co. 3 )alkyl,- (C 6 -ιo)aryl(Co. 6 )alkyl, hetero(C 5 . 10 )aryl(Co. 6 )alkyl, (C 9 .ι 2 )bicycloaryl(C 0 - 6 )alkyl or hetero(C 8 . 12 )bicycloaryl(C 0 - 6 )alkyl; wherem within R 3 and R 4 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical selected from -R 15 and -X 4 OR 15 , wherein X 4 and R 15 are as defined above; and wherein R 3 and R 4 may be substituted further by 1 to 5 radicals independently selected from (Cι. 6 )alkyl, cyano, halo, halo-substituted(Cι. 4 )alkyl, -X 4 NR 12 C(O)OR 12 , -X 4 OR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X C(O)NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 and -X 4 S(O) 2 R 14 , wherein X 4 R 12 , R 13 and R 14 are as defined above; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 4. A compound of claim 3 in which R 3 is selected from 5-bromo-thiophen-2- ylmethyl, 3-cyclohexylpropyl, 2-cyclohexylpropyl, 2-cyclopentylpropyl, 3-phenylpropyl, 3-(2-difluoromethoxy)phenylpropyl, 2-phenylcyclopropylmethyl, 2,2-difluoro- 3-phenylpropyl, 1 -benzylcyclopropylme thy, 2- tettahydro-pyran-4-yle thyl, 1 -isobutylcyclopropylmethyl, thiophen-2-ylmethyl, tetrahydro-pyran-4-ylmethyl, cyclopropylmethylsulfanylmethyl, 2,2-dimethyl-3-phenylpropyl, 4-methyl- [1 ,2,5]thiadiazol-3-ylmethylsulfonylmethyl, 3-methyl-[l ,2,4] fhiadiazol-3- ylmethylsulfonylmethyl, thiophen-3-ylmethylsulfonylmethyl, 3-methoxy-5-methyl- isoxazol-4-ylmethylsulfonylmethyl, 2,4-dimethyl-thiazol-5-ylmethylsulfonylmethyl, 2- methyl-oxazol-4-ylmethylsulfonylmethyl, 2-methyl-thiazol-4-ylmethylsulfonylmethyl„ l,2,3]thiadiazol-4-ylmethylsulfonylmethyl, 3-methyl-[l,2,4]thiadiazol-5- ylmethylsulfonylmemyl,4-methyl-[l,2,5]lMadiazol-3-ylmethylsulfonylmemyl,thiophen-3- ylmethylsulfonylmethyl, tetrahydro-pyran-4-yloxymethyl, piperidin-1-ylcarbonyl, thiophene-2-sulfonylmethyl, 3-chloro-2-fluoro-benzylsulfonylmethyl, benzenesulfonylmethyl, benzylsulfonylmethyl, 2-( 1 , 1 -difluoro-methoxy)-benzylsulfonylmetlιyl, 2-benzenesulfonyl-ethyl, 2-(pyridine-2-sulfonyl)-ethyl, 2-(pyridine-4-sulfonyl)-ethyl, 2-benzylsulfonyl-ethyl, oxy-pyridin-2-ylmethylsulfonylmethyl, prop-2-ene-l-sulfonylmethyl, 4-methoxy-benzylsulfonylmethyl, p-tolylmethylsulfonylmethyl, 4-chloro-benzylsulfonylmethyl, o-tolylmethylsulfonylmethyl, 3,5-dimethyl-benzylsulfonylmethyl, 4-ttifluoromethyl-benzylsulfonylmethyl, 4-ttifluoromethoxy-benzylsulfonylmethyl, 2-bromo-benzylsulfonylmethyl, pyridin-2-ylmethylsulfonylmethyl, pyridin-3-ylmethylsulfonylmethyl, pyridin-4-ylmethylsulfonylmethyl, naphthalen-2-ylmethylsulfonylmethyl, 3-methyl-benzylsulfonylmethyl, 3-ttifluoromethyl-benzylsulfonylmethyl, 3-trifluoromethoxy-benzylsulfonylmethyl, 4-fluoro-2-trifluoromethoxy-benzylsulfonylmethyl 2-fluoro-6-trifluoromethyl-benzylsulfonylmethyl, 3-chloro-benzylsulfonylmethyl, 2-fluoro-benzylsulfonylmethyl, 2-trifluoro-benzylsulfonylmefhyl, 2-cyano-benzylsulfonylmethyl, 4-tert-butyl-benzylsulfonylmethyl, 2-fluoro-3-methyl-benzylsulfonylmethyl, 3-fluoro-benzylsulfonylmethyl, 4-fluoro-benzylsulfonylmethyl, 2-chloro-benzylsulfonylmethyl, 2,5-difluoro-benzylsulfonylmethyl, 2,6-difluoro-benzylsulfonylmethyl, 2,5-dichloro-benzylsulfonylmethyl, 3,4-dichloro-benzylsulfonylmethyl, 2-( 1 , 1 -difluoro-methoxy)-benzylsulf onylmethyl, 2-cyano-benzylsulfonylmethyl, 3-cyano-benzylsulfonylmethyl, 2-trifluoromethoxy-benzylsulfonylmethyl, 2,3-difluoro-benzylsulfonylmethyl, 2,5-difluoro-benzylsulfonylmethyl, biphenyl-2-ylmethylsulfonylmethyl, cyclohexylmethyl, 3-fluoro-benzylsulfonylmethyl, 3,4-difluoro-benzylsulfonylmethyl, 2,4-difluoro-benzylsulfonylmethyl, 2,4,6-trifluoro-benzylsulfonylmethyl, 2,4,5-trifluoro-benzylsulfonylmethyl, 2,3,4-trifluoro-benzylsulfonylmethyl, 2,3,5-ttifluoro-benzylsulfonylmethyl, 2,5,6-ttifluoro-benzylsulfonylmethyl, 2-chloro-5-trifluoromethylbenzylsulfonylmethyl, 2-methyl-propane- 1 -sulfonyl, 2-fluoro-3-ttifluoromethylbenzylsulfonylmethyl, 2-fluoro-4-trifluoromethylbenzylsulfonylmethyl, 2-fluoro-5-ttifluoromethylbenzylsulfonylmethyl, 4-fluoro-3 -ttifluoromethylbenzylsulfonylmethyl, 2-methoxy-benzylsulf onylmethyl, 3 , 5 bis-trifluoromethyl-benzylsulfonylmethyl, 4-difluoromethoxy-benzylsulfonylmethyl, 2-difluoromethoxy-benzylsulfonylmethyl, 3-difluoromethoxy-benzylsulfonylmethyl, 2,6-dichloro-benzylsulfonylmethyl, biphenyl-4-ylmethylsulfonylmethyl, 3,5-dimethyl-isoxazol-4-ylmethylsulfonylmethyl, 5-chloro-thiophen-2-ylmethylsulfonylmethyl, 2-[4-(lJ-Difluoro-methoxy)-benzenesulfonylj-ethyl, 2-[2-( 1 , 1 -Difluoro-methoxy)-benzenesulfonyl] -ethyl, 2-[3-(l , l-Difluoro-methoxy)-benzenesulfonyl] -ethyl, 2-(4-teifluoromethoxy-benzenesulfonyl)-ethyl, 2-(3-ttifluoromethoxy-benzenesulfonyl)-ethyl, 2-(2-ttifluoromethoxy-benzenesulfonyl)-ethyl, (cyanomethyl-methyl-carbamoyl)-methyl, biphenyl-3-ylmethyl, 2-oxo-2-pyrrolidin- 1 -yl-ethyl, 2-benzenesulfonyI-ethyI, isobutylsulfanylmethyl, 2-phenylsulfanyl-ethyl, cyclohexylmethylsulfonylmethyl, 2-cyclohexyl-ethanesulfonyl, benzyl, naphthalen-2-yl, benzylsulfanylmethyl, 2-trifluoromethyl-benzylsulfanylmethyl, phenylsulfanyl-ethyl and cyclopropylmethylsulfonylmethyl; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 5. A compound of claim 4 in which R 4 is selected from 2-trifluorobenzylsulfonylmethyl, 3-phenylsulfanylpropyl, 4-chlorobenzylsulfonylmethyl, thiophen-2-ylsulfonylmethyl, benzylsulfonylmethyl, 4-methylbenzylsulfonylmethyl, 2-phenylsulfonylethyl, 2-pyridm-2-ylsulfonylethyl, 2-pyridin-4-ylsulfonylethyl, 2-benzylsulfonylethyl, 2-(3-difluoromethoxyphenylsulfonyl)ethyl, naphthalen-2-ylmethylsulfonylmethyl, pyridin-2-ylmethylsulfonylmethyl, 3-methylbenzylsulfonylmethyl, 3-trifluoromethylbenzylsulfonylmethyl, 3-difluoromethoxybenzylsulfonylmethyl, 3-chlorobenzylsulfonylmethyl, 3-fluorobenzylsulfonylmethyl, 4-fluorobenzylsulfonylmethyl, 3-cyanobenzylsulfonylmethyl, 4-cyanobenzylsulfonylmethyl, 3 ,4-difluorobenzylsulfonylmethyl, benzylsulfonylmethyl, N-cyanomethyl-N-methylcarbamoylmethyl, 3-bromobenzyl, 4-phenylbutyl, 2,2-difluoro- 3-phenylpropyl, 4'-methylsulfonylaminobiphenyl-3-ylmethyl, 4'-ethoxycarbonylaminobiphenyl-3-ylmethyl, 4-methylpiperazin-l-ylcarbonylmethyl, 1 -fluoro-2-(4-mefhylpiperazin- 1 -yl)-2-oxoethyl, 1 -hydroxy-4-methylpiperazin- 1 -yl- 2-oxoethyl, 1 -hydroxy-2-moφholin-4-yl-2-oxoethyl, 1 -hydroxy-2-oxo-2-pyrrolidin- 1 -yl- ethyl, l-fluoro-2-oxo-2-pyrrolidin-l-yl-etl yl, l-fluoro-2-isopropylamino-2-oxoethyl, 1 -hydroxy-2-isopropylamino-2-oxoethyl, 1 -fluoro-2-oxo-2-piperazin- 1 -ylethyl, thiophen-3-ylmethylsulfonylmethyl,4-methyl-[l,2,5]thiadiazol-3-ylmethylsulfonylmethyl, 3-methoxy-5-methyl-isoxazol-4-ylmethylsulfonylmethyl, 2,4-dimethyl-thiazol-5- ylmethylsulfonylmefhyl, 2-methyl-oxazol-4-ylmethylsulfonylmethyl, 2-methyl- thiazol-4-ylmethylsulfonylmethyl, 2-([ 1 ,2,3 ]thiadiazol-4-ylmethylsulfonyl)-ethyl, 2-(3- methyl-[l,2,4]thiadiazol-5-ylmethylsulfonyl)-ethyl, 2-oxo-2-phenyl-ethyl, 2-moφholin-4-yl-2-oxo-ethyl, 2-benzenesulfonyl-ethyl, 2-naphthalen-2-yl-2-oxo-ethyl, 2-benzo[ 1 ,3]dioxol-5-yl-2-oxo-ethyl, 2-benzo[b]thiophen-2-yl-2-oxo-ethyl, 2-biphenyl-4-yl-2-oxo-ethyl, 4-benzylsulfonylmethyl, 2-(3-teifluoromethoxy-benzenesulfonyl)-ethyl, 2-oxo-2-(4-phenoxy-phenyl)-ethyl, 2-(4-hydroxy-phenyl)-2-oxo-ethyl, benzylcarbamoyl-methyl, 4-acetyl-piperazine-l -carboxylic acid ethyl ester, cyclohexylcarbamoylmethyl, 2-(3-Chloro-benzo[b]thiophen-2-yl)-2-oxo-ethyl, benzenesulfonylmethyl, 2-oxo-2-thiophen-2-yl-ethyl, 2-oxo-2-thioρhen-3-yl-ethyl,naphthalene-2-sulfonylmethyl, 2-(5-methyl-fhiophen-2-yl)-2-oxo-ethyl, 2-(3-chloro-thiophen-2-yl)-2-oxo-ethyl, 5-methyl-thiophene-2-sulfonylmethyl, phenylcarbamoylmethyl, (5, 6,7, 8- tettahydro-naphthalen- 1 -ylcarbamoyl)-me fhyl, (4-carbamoyl-phenylcarbamoyl)-methyl, (3-carbamoyl-phenylcarbamoyl)-methyl, (butyl-methyl-carbamoyl)-methyl, biphenyl-4-ylmethyl, 2-oxo-2-/.-tolyl-ethyl, 2-(3-fluoro-4-methoxy-phenyl)-2-oxo-ethyl, 2-(4-chloro-phenyl)-2-oxo-ethyl, 2-(4-methoxy-phenyl)-2-oxo-ethyl, 2-oxo-2-(4-trifluoromethoxy-phenyl)-ethyl, 2-(3,4-difluoro-phenyl)-2-oxo-ethyl, 2-(3,4-dimethoxy-phenyl)-2-oxo-ethyl, 2-(4-fluoro-phenyl)-2-oxo-ethyl, 5-methyl-2-oxo-hexyl, 3,5-dimethyl-benzylsulfonylmethyl, 4-ttifluoromethyl-benzylsulfonylmethyl; 4-trifluoromethoxy-benzylsulfonylmethyl, isopropylcarbamoyl-methyl, 4-dimethylcarbamoylmethyl, pyridin-4-ylcarbamoylmethyl, pyridin-4-ylmethylsulfonylmethyl, ρyridin-3-ylmethylsulfonylmethyl, 3,4-dichloro-benzylsulfonylmethyl, pyridin-3-ylcarbamoylmethyl, 4-methoxy-benzylsulfonylmethyl, 4-chloro-benzylsulfonylmethyl, thiophene-2-sulfonylmethyl, benzylsulfonylmethyl, p-tolylmethylsulfonylmethyl, 2-benzenesulfonyl-ethyl, 2-(pyridine-2-sulfonyl)-ethyl, 2-(pyridine-4-sulfonyl)-ethyl, 2-benzylsulfonyl-ethyl, 2-[3-(lJ-Difluoro-methoxy)-benzenesulfonyl]-ethyl, naphthalen-2-ylmethylsulfonylmethyl, pyridin-2-ylmethylsulfonylmethyl, m-tolylmethylsulfonylmethyl, 3-ttifluoromethyl-benzylsulfonylmethyl, 3-ttifluoromethoxy-benzylsulfonylmethyl, 3-chloro-benzylsulfonylmethyl, 3-fluoro-benzylsulfonylmethyl, 4-fluoro-benzylsulfonylmethyl, 3-cyano-benzylsulfonylmethyl, 4-cyano-benzylsulfonylmethyl, 3 ,4-difluoro-benzylsulf onylmethyl, (cyanomethyl-methyl-carbamoyl)-methyl, 3-bromo-benzyl, 2-oxo-2-pyrrolidin-l -yl-ethyl, 2-(4'-chloro-biphenyl-4-yl)-2-oxo-ethyl, biphenyl-3-ylmethyl, 2-(l J-difluoro-methoxy)-benzylsulfonylmef_ιyl, 2-(4-me thylsulf onylamino-phenyl)-2-oxo-ethyl, 2-oxo-2-piperidin- 1 -yl-ethyl, 2-(4-methylsulf onyl-piperazin- 1 -yl)-2-oxo-ethyl, 2-1rifluoromethyl-benzylsulfonylmethyl, 4-fluoro-3-trifluoromethyl-benzylsulfonylmethyl, 4-carboxy-benzylsulfonylmethyl, 3,5-bis-trifluoromethyl-benzylsulfonylmethyl, 4-(l , l-difluoro-methoxy)-benzylsulfonyImethyl, 3-(l , 1 -difluoro-methoxy)-benzylsulfonylmethyl, 5-chloro-thiophen-2-ylmethylsulfonylmethyl, 2-[4-(lJ-difluoro-methoxy)-benzenesulfonyl]-ethyl, 2-(4-trifluoromethoxy-benzenesulfonyl)-ethyl, 2-phenylsulfanyl-ethyl, benzylsulfanylmethyl, 2-trifluoromethyl-benzylsulfanylmethyl, 2-trifluoromethoxy-benzylsulfanylmethyl, 2-cyclohexyl-ethyl and isobutylsulfanylmethyl; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 6. The compound of claim 5 in which R 1 is hydrogen or (Cι_ 6 )alkyl and R 2 is hydrogen, -X 4 OR 13 , hetero(C 5 .ι 0 )aryl(Co. 6 )alkyl, (C5.ι 0 )aryl(Co. 6 )alkyl or (Cι. 6 )alkyl; or R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene or hetero(C 3 . 8 )cycloalkylene; wherem the cycloalkylene or heterocycloalkylene are optionally substituted with 1 to 3 (Cι. 6 )alkyl radicals; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 7. The compound of claim 6 in which R 1 is hydrogen or methyl and R 2 is methoxymethyl, methoxyethyl, methyl, ethyl, propyl, butyl, phenethyl, hiophen-2-yl or 5- methyl-furan-2-yl; or R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form cyclopropyl, tettahydro-pyran-4-yl or l-methyl-piperidin-4-yl; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 8. The compound of claim 7 of Formula 1(a) : 1(a) and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 9. The compound of claim 8 selected from the group consisting of 3-biphenyl- 3-yl-N-cyanomethyl-2-benzylsulfonylmethyl-propionamide; 3-biphenyl-4-yl-N- cyanomethyl-2-benzylsulfonylmethyl-propionamide; 3-(3-bromo-phenyl)-N-cyanomethyl- 2-benzylsulfonylmethyl-propionamide; N-cyanomethyl-3-(3-cyano-benzylsulfonyl)-2- benzylsulfonyl-methyl-propionamide; N-cyanomethyl-2-[2-l J-difluoro-methoxy)- benzylsulfanylmethyl]-3-benzylsulfanyl-propionamide; N-cyanomethyl-3-(2- trifluoromethyl-benzylsulfanyl)-2-(2-ttifluoro-methyl-benzylsulfanylmethyl)- propionamide;N-cyanomethyl-3-isobutylsulfanyl-2-isobutylsulfanylmemyl-propionamide; N-cyanomethyl-4-phenylsulfanyl-2-(2-phenylsulfanyl-ethyl)-butyramide;N-cyanomethyl- 3- [2-( 1 , 1 -difluoro-methoxy)-benzylsulf anyl] -2- [2-(l , 1 -difluoro-methoxy)- benzylsulfanylmethyl]-propionamide; 3-benzylsulfanyl-2-benzylsulfanylmethyl-N- cyanomethyl-propionamide; N-cyanomethyl-2-[2-l,l-difluoro-methoxy)- benzylsulfonylmethyl]-3-benzylsulfonyl-propionamide; N-cyanomethyl-3-(2- trifluoromemyl-beι__ylsulfonyl)-2-(2-trifluoromethyl-ber__ylsulfonylmemyl)-propionamide; 4-benzenesulfonyl-2-(2-benzenesulfonyl-ethyl)-N-cyanomethyl-butyramide; N- cyanomethyl-3-[2-(lJ-difluoro-methoxy)-benzylsulfonyl]-2-[2-(lJ-difluoro-methoxy)- benzylsulfonylmethylj-propionamide; N-cyanomethyl-3-benzylsulfonyl-2- benzylsulfonylmethyl-propionamide;N-cyanomethyl-3-(2-methyl-propane-l-sulfonyl)-2- (2-methyl-propane-l-sulfonylmethyl)-propionamide;N-cyanomethyl-3-(2-methyl-thiazol- 4-ylmethylsulfonyl)-2-benzyl-sulfonylmethyl-propionamide; 3-biphenyl-3-yl-N- cyanomethyl-2- [2-( 1 , 1 -difluoro-methoxy)-benzyl-sulfonylmethyl] -propionamide; (3'- { 2- (cyanomethyl-carbamoyl)-3-[2-(l,l-difluoro-mefhoxy)-benzyl-sulfonyl]-propyl}-biphenyl- 4-yl)-carbamic acid ethyl ester; N-cyanomethyl-2-[2-(l,l-difluoro-methoxy)- benzylsulfonylmethyl]-3-(4'-methylsulfonylamino-biphenyl-3-yl)-propionamide; 3-(3- bromo-phenyl)-N-cyanomethyl-2-[2-(l,l-difluoro-methoxy)-phenyl- methylsulfonylmethyl]-propionamide; N-cyanomethyl-2-((E)-3-phenyl-allyl)-3- benzylsulfonyl-propionamide; and N-cyanomethyl-3-benzylsulfonyl-2-(3-phenyl-propyl)- propionamide; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 10. The compound of Claim 7 of Formula 1(b): 1(b) and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 11. The compound of claim 10 in which R 5 is lH-benzoimidazol-2-yl, benzooxazol-2-yl, oxazolo[4,5-b]pyridin-2-yl, benzothiazol-2-yl, 5-phenyl- [l,3,4]oxadiazol-2-yl, 4-(5-pyridin-4-yl-[l,3,4]oxadiazol-2-yl, 5-pyridin-3-yl- [l,3,4]oxadiazol-2-yl, 5-pyridazin-3-yl-[l,3,4]oxadiazol-2-yl,pyrimidin-2-yl,pyridazin-3- yl, 3-penyl-[l,2,4]oxadiazoI-5-yl, 5-methoxymethyI-[l,3,4]oxadiazol-2-yl, 5-ethyl- [l,3,4]oxadiazol-2-yl„ l,3,4]thiadiazol-2-yl, benzyloxycarbonyl, benzyloxydicarbonyl, phenyldicarbonyl, 5-methyl-[l,3,4]thiadiazol-2-yl, 5-trifluoromethyl-[l,3,4]oxadiazol-2-yl, 5-mefhyl-[l,3,4]oxadiazol-2-yl, 5-methyl-[l,2,4]oxadiazol-3-yl,5-phenyl-[l,2,4]oxadiazol- 3-yl, 5--hiophen-3-yl-[l,2,4]oxadiazol-3-yl, 5-ttifluoromethyl-[l,2,4]oxadiazol-3-yl, 3- methyl-[l,2,4]oxadiazol-5-yl or 3-pyrazin-2-yl; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 12. The compound of claim 11 selected from the group consisting of N-[(S)- 1 - (l-Benzooxazol-2-yl-methanoyl)-butyl]-3-benzylsulfonyl-2-benzylsulfonylmethyl- propionamide; N-[(S)-l-(l-Benzooxazol-2-yl-methanoyl)-butyl]-3-(2-trifluoromethyl- benzylsulfonyl)-2-(2-ttifluoromethyl-benzylsulfonylmethyl)-propionamide; N-[(S)-l-(l- Benzooxazol-2-yl-methanoyl)-pentyl]-4-(2-methoxy-benzenesulfonyl)-2-[2-(2-methoxy- benzenesulfonyl)-ethyl]-butyramide; 4-Benzenesulfonyl-2-(2-benzenesulfonyl-ethyl)-N- [(S)-l-(l-benzooxazol-2-yl-methanoyl)-butyl]-butyrarnide; (R)-N-[(S)-l-(l-benzooxazol-2- yl-methanoyl)-butyl]-2-cyclohexylmethyl-3-benzylsulfonyl-propionamide; N-[(S)-1-(1- benzothiazol-2-yl-methanoyl)-propyl]-4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl- butyramide; N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-butyl]-3-cyclohexyl-2- cyclohexylmethyl-propionamide; N-[(S)-l-(l-Benzooxazol-2-yl-methanoyl)-butyl]-3- isobutylsulfanyl-2-isobutylsulfanylmethyl-propionamide;N-[(S)-l-(l-benzooxazol-2-yl- methanoyl)-butyl]-3-benzylsulfanyl-2-benzylsulfanylmethyl-propionamide; N-[(S)-l-(l- benzooxazol-2-yl-methanoyl)-butyl]-4-phenylsulfanyl-2-(2-phenylsulfanyl-efhyl)- bui^amide;N-[(S)-l-(l-benzooxazol-2-yl-methanoyl)-propyl]-4-moφholin-4-yl-4-oxo-2- benzylsulf onylmethyl-bu tyramide; N- [(S)- 1 -( 1 -Benzooxazol-2-yl-methanoyl)-pentyl] -4- moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyramide; 4-Moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-N-{(S)-l-[l-(3-ρhenyl-[l,2,4]oxadiazol-5-yl)-methanoyl]-propyl}- butyramide; N-[(S)-l-(l-Benzooxazol-2-yl-methanoyl)-butyl]-2-[2-(l,l-difluoro-methoxy)- benzylsulfonylmethyl]-3-benzylsulfonyl-propionamide;4-Moφholin-4-yl-4-oxo-N-[l-(2- oxo-2-phenyl-acetyl)-pentyl] -2-benzylsulf onylmethyl-butyramide; N-( 1 , 1 -Dimethyl-2- oxazolo[4,5-b]pyridin-2-yl-2-oxo-ethyl)-4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl- butyramide; N-[l-(5-Ethyl-[l,3,4]oxadiazole-2-carbonyl)-butyl]-4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyraniide; N-[l-(5-Ethyl-[l,3,4]oxadiazole-2-carbonyl)-butyl]-4- oxo-2-benzylsulfonyl-methyl-4-piperidin-l-yl-butyramide; N-[l-(5-Ethyl- [ 1 ,3 ,4] oxadiazole-2-carbonyl)-butyl] -4-oxo-2-benzylsulf onyl-methyl-4-pyrrolidin- 1 -yl- butyramide; N-[l-(5-Methoxymethyl-[l,3,4]oxadiazole-2-carbonyl)-propyl]-4-moφholin- 4-yl-4-oxo-2-benzyIsulfonylmethyl-butyramide; N-[l-(5-Methoxymethyl- [l,3,4]oxadiazole-2-carbonyl)-propyl1-4-oxo-2-benzylsulfonylmethyl-4-piperidin-l-yl- butyramide; N- [ 1 -(5 -Methoxymethyl- [ 1 ,3 ,4] oxadiazole-2-carbonyl)-propyl] -4-oxo-2- benzylsulf onylmethyl-4-pyrrolidin- 1 -yl-butyramide; 4-Moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-N-[l-(5-phenyl-[l,3,4]oxadiazole-2-carbonyl)-propyl]-butyramide; 4-Oxo-2-benzylsulf onylmethyl-N-[ 1 -(5-phenyl- [ 1 ,3 ,4] oxadiazole-2-carbonyl)-propyl] -4- piperidin- 1-yl-butyramide; 4-Oxo-2-benzylsulfonylmethyl-N-[l-(5-phenyl- [l,3,4]oxadiazole-2-carbonyl)-propyl]-4-pyrrolidin-l-yl-butyramide;4-Moφholin-4-yl-N- [l-(oxazolo[4,5-b]pyridine-2-carbonyl)-propyl]-4-oxo-2-ber_zylsulfonylmemyl-butyramide; N-[l-(Oxazolo[4,5-b]pyridine-2-carbonyl)-propyl]-4-oxo-2-benzylsulfonyl-methyl-4- piperidin- 1-yl-butyramide; N-[l-(Oxazolo[4,5-b]pyridine-2-carbonyl)-propyl]-4-oxo-2- benzylsulfonyl-methyl-4-pyrrolidin-l-yl-butyramide; 4-Mθφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-N-[l-(5-pyridin-4-yl-[l,3,4]oxadiazole-2-carbonyl)-propyl]- butyramide; 4-Oxo-2-benzylsulfonylmethyl-4-piperidin-l-yl-N-[l-(5-pyridin-4-yl- [l,3,4]oxadiazole-2-carbonyl)-propyl]-butyramide; 4-Oxo-2-benzylsulfonylmethyl-N-[l- (5-pyridin-4-yl-[l,3,4]oxadiazole-2-carbonyl)-propyl]-4-pyrrolidin-l-yl-butyramide; 4- Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-[l-(5-pyridin-3-yl-[l,3,4]oxadiazole-2- carbonyl)-propyl] -butyramide; N-[l-(Benzooxazole-2-carbonyl)-propyl]-4-oxo-2- benzylsulfonylmethyl-4-piperidin- 1-yl-butyramide; N-[l-(Benzooxazole-2-carbonyl)- propyl]-4-oxo-2-ber_zylsulfonylmethyl-4-pyrrolidin-l-yl-butyramide;N-[l-(Benzooxazole- 2-carbonyl)-propyl]-2-cyclohexylmethyl-4-moφholin-4-yl-4-oxo-butyramide; 2- Cyclohexylmethyl-4-moφholm-4-yl-N-[l-(oxazolo[4,5-b]pyridine-2-carbonyl)-propyl]-4- oxo-butyramide; 2-Cyclohexy_methyl-Ν-[l-(5-ethyl-[l,3,4]oxadiazole-2-carbonyl)-butyl]- 4-moφholin-4-yl-4-oxo-butyramide; N-(2-Benzooxazol-2-yl-l-methoxymethyl-2-oxo- ethyl)-2-(2-difluoromethoxy-benzylsulfonylmemyl)-4-moφholin-4-yl-4-oxo-butyrarnide; N-[l-(Benzooxazole-2-carbonyl)-propyl]-2-(2-cyclohexyl-ethyl)-4-moφholin-4-yl-4-oxo- butyramide; 2-(2-Cyclohexyl-ethyl)-4-moφholin-4-yl-N-[l-(oxazolo[4,5-b]pyridine-2- carbonyl)-propyl]-4-oxo-butyrarnide; 2-(2-Cyclohexyl-ethyl)-4-moφholin-4-yl-4-oxo-N- [l-(5-phenyl-[l,3,4]oxadiazole-2-carbonyl)-propyl]-butyramide; 2-(2-Difluoromethoxy- benzylsulf onylme thyl)-4-moφholin-4-yl-4~oxo-N- [ 1 -(5-phenyl- [ 1 ,3 ,4] oxadiazole-2- carbonyl)-propyl] -butyramide; 2-(2-Difluoromethoxy-benzylsulfonylmethyl)-N-[ 1 -(5-ethyl- [ 1 ,3 ,4] oxadiazole-2-carbonyl)-butyl] -4-moφholin-4-yl-4-oxo-butyramide; N- [ 1 - (Benzooxazole-2-carbonyl)-propyl]-2-(2-difluoromethoxy-benzyl-sulfonylmethyl)-4- moφholin-4-yl-4-oxo-butyr amide; 2-(2-Moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, l-(benzooxazole-2- carbonyl)-propyl]-amide; (R)-2-Cyclohexylmethyl-4-moφholin-4-yl-4-oxo-N-[(S)-l-(5- phenyl- l,2,4-oxadiazole-3-carbonyl)-proρyl] -butyramide; 2-(2-Moφholin-4-yl-2-oxo- ethyl)-5 -phenyl-pentanoic acid, (S)-l-(5-ρhenyl-[l,2,4]oxadiazole-3-carbonyl)-propyl]- amide; 4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-[(S)-l-(5-phenyl-l,2,4- oxadiazole-3-carbonyl)-propyl]-butyramide; (R)-2-Cyclohexylmefhyl-4-moφholin-4-yl-4- oxo-N-[(S)-l-(3-phenyl-l,2,4-oxadiazole-5-C-u:bonyl)-propyl]-bU-yramide; 4-Moφholin-4- yl-N-[l-(oxazole-2-carbonyl)-3-phenyl-propyl]-4-oxo-2-benzylsulfonylmemyl-butyramide; N-(lJ-Dimethyl-2-oxazol-2-yl-2-oxo-ethyl)-4-moφholin-4-yl-4-oxo-2- benzylsulf onylmethyl-butyr amide; N-4-Isopropyl-N- 1 - [ 1 -(oxazole-2-carbonyl)-3-phenyl- propyl]-2-benzylsulfonylmethyl-succinamide; 2-(2-Difluoromethoxy- benzylsulfonylmethyl)-4-moφholin-4-yl-N-[l-(oxazole-2-carbonyl)-3-phenyl-propyl]-4- oxo-butyramide; 2-(2-Methyl-ρropane-l-sulfonylmethyl)-4-moφholin-4-yl-N-[l-(oxazole- 2-C-u:bonyl)-3-phenyl-propyl]-4-oxo-butyramide; 2-Cyclopropylmethylsulfonylmethyl-4- moφholin-4-yl-N- [ 1 -(oxazole-2-carbonyl)-3-phenyl-propy 1] -4-oxo-butyramide; N-[ 1 - (Benzooxazole-2-carbonyl)-butyl]-2-benzylsulfonyl-3-(tettahydro-pyran-4-yloxymethyl)- propionamide; N-[l-(Benzooxazole-2-carbonyl)-butyl]-3-ethanesulfonyl-2-(tettahydro- pyran-4-yloxymethyl)-propionamide; N-(l-Benzenesulfonyl-3-oxo-azepan-4-yl)-2- cyclopropylmethylsulfonyl-methyl-4-moφholin-4-yl-4-oxo-butyramide; 2- Cyclopropylme thylsulfonylme thyl-Ν- { (S)- 1 -[(R)-hydroxy-(3-phenyl- 1 ,2,4-oxadiazol-5-yl)- methyl] -propyl } -4-moφholin-4-yl-4-oxo-butyramide; N- { (S)- 1 -[(R)-hydroxy-(3-phenyl- l,2,4-oxadiazol-5-yl)-methyl]-propyl}-2-(2-methyl-propane-l-sulfonylmethyl)-4- moφholin-4-yl-4-oxo-butyramide; 2-(2-Moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid {(S)-l-[(R)-hydroxy-(3-phenyl-l,2,4-oxadiazol-5-yl)-methyl]-propyl}-amide; 2- Cyclopropylmethylsulfonylmethyl-4-moφholin-4-yl-4-oxo-Ν-[(S)-l-(3-phenyl-l,2,4- oxadiazole-5-carbonyl)-propyl]-butyramide; 2-(2-methyl-propane-l-sulfonylmethyl)-4- moφholin-4-yl-4-oxo-N-[(S)-l-(3-phenyl-l,2,4-oxadiazole-5-carbonyl)-propyl]- butyramide; 2-(2-Moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, (S)-l-(3-phenyl- l,2,4-oxadiazole-5-carbonyl)-propyl}-amide; N-[(lS)-l-(Benzooxazol-2-yl-hydroxy- methyl)-3-phenyl-propyl]-2-cyclopropylmethylsulfonylmethyl-4-moφholin-4-yl-4-oxo- butyramide; (R)-2-((S)-l -Hydroxy-2-moφholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid, l-(benzoxazole-2-carbonyl)-propyl]-amide; (R)-5-(2-Difluoromethoxy-phenyl)-2-((S)-l- hydroxy-2-moφholin-4-yl-2-oxo-ethyl)-ρentanoic acid, l-(benzoxazole-2-carbonyl)- propyl] -amide; and 4-Mθφholin-4-yl-Ν-[l-(oxazole-2-carbonyl)-cyclopropyl]-4-oxo-2- benzylsulfonyl methyl -butyramide; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 13. The compound of claim 7 of Formula 1(c) : 1(c) and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 14. The compound of claim 13 in which R 5 is phenyl; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 15. The compound of claim 14 selected from the group consisting of N-[(S)-1- ((E)-2-benzenesulfonyl-vinyl)-pentyl]-3-benzylsulfonyl-2-benzylsulfonylmethyl- propionamide and N-(3-benzenesulfonyl-l-phenethyl-allyl)-3-benzylsulfonyl-2- benzylsulfonylmethyl-propionamide; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 16. The compound of claim 7 of Formula 1(d) : 1(d) and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 17. The compound of claim 16 in which R 5 is phenyl and R 6 is hydrogen; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 18. The compound of claim 17 namely N-(3-benzenesulfonylamino-2-oxo- propyl)-4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyramide; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 19. The compound of claim 7 of Formula 1(e): and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 20. The compound of claim 19 in which R 5 and R 6 is methyl; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 21. The compound of claim 20 in which one X 7 is moφholine-4-carbonyl and the other is benzylsulfonyl, R 1 is hydrogen and R 2 is ethyl, namely (S)-2,2-difluoro-4-(4- moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butanoylamino)-3-oxo-hexanoic acid dimethylamide; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 22. The compound of claim 7 of Formula 1(f): 1(f) and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 23. The compound of claim 22 in which R 5 is methyl, benzyl, phenethyl, cyclohexyl, methoxyethyl, dimethylaminoethyl, tetrahydro-pyran-4-yl, 1-methylsulfonyl- piperidin-4-yl, 4-methyl-piperazin-l-yl, moφholin-4-ylethyl, pyridin-2-yl, pyridin-2- ylmethyl or oxazol-2-ylmethyl; R 6 is hydrogen or methyl; or R 5 and R 6 together with the nitrogen atom to which both R 5 and R 6 are attached form moφholine-4-yl, pyrrolidin-1-yl, 4-dimethylamino-piperazin- 1 -yl, 4-hydroxy-piperazin- 1 -yl, 4-pyridin-2-yl-piperazm- 1 -yl, 4-benzoyl-piperazin-l-yl or 3-oxo-piperazin-l-yl; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 24. The compound of claim 23 selected from the group consisting of N-[(S)-1- (l-Benzylcarbamoyl-methanoyl)-propyl]-3-benzylsulfonyl-2-benzylsulfonylmethyl- propionamide andN-[(S)-l-(l-Benzylcarbamoyl-methanoyl)-propyl]-4-moφholin-4-yl-4- oxo-2-benzylsulfonylmethyl-butyramide; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 25. The compound of claim 7 of Formula 1(g) : 1(g) and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 26. The compound of claim 25 in which X 3 is l-benzoyl-4-oxo-pyrrolidin-3-yl, 4-oxo-pyrrolidin-3-yl-l -carboxylic acid tert-butyl ester, 2-methyl-4-oxo-tetrahydro-furan- 3-yl, 2-ethyl-4-oxo-teteahydro-furan-3-yl, 4-oxo-teteahydro-furan-3-yl, 2-acetoxy-4-oxo- azetidin-3-yl, l-isopropyl-3-oxo-azepan-4-yl, 3-oxo-azepan-4-yl-l-carboxylic acid benzyl ester, 3-oxo-azepan-4-yl-l-carboxylic acid tert-butyl ester, l-benzoyl-3-oxo-azepan-4-yl, 1- isobu tyryl-3-oxo-azepan-4-yl, 3-oxo- 1 -(propane-2-sulfonyl)-azepan-4-yl, 1 - benzenesulfonyl-3-oxo-azepan-4-yl, l-benzenesulfonyl-3-oxo-piperidin-4-yl, 1- benzenesulfonyl-4-oxo yrrolidin-3-yl, l-benzoyl-3-oxo-piperidin-4-yl or 3-oxo- tettahydro-pyran-4-yl; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 27. The compound of claim 23 selected from the group consisting of 3- Hydroxy-4-(4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyrylamino)-azepane-l- carboxylic acid tert-butyl ester; 4-(2-Cyclopropylmethylsulfonylmethyl-4-moφholin-4-yl- 4-oxo-butyrylamino)-3-hydroxy-azepane-l-carboxylic acid tert-butyl ester; 3-Hydroxy-4- [2-(2-methyl-propane-l-sulfonylmethyl)-4-moφholin-4-yl-4-oxo-butyrylamino]-azepane- 1-carboxylic acid tert-butyl ester; 4-(4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl- butyrylamino)-3-oxo-azepane-l-carboxylic acid tert-butyl ester; 4-(2- Cyclopropylmethylsulfonylmemyl-4-moφholin-4-yl-4-oxo-butyrylamino)-3-oxo-azepane- 1-carboxylic acid tert-butyl ester; 4-[2-(2-Methyl-propane-l-sulfonylmethyl)-4-moφholin- 4-yl-4-oxo-butyrylamino]-3-oxo-azepane-l -carboxylic acid tert-butyl ester; N-(l- Benzenesulfonyl-3-oxo-azepan-4-yl)-4-moφholin-4-yl-4-oxo-2-benzylsulfonylmethyl- butyramide; N-(l-Benzenesulfonyl-3-oxo-azepan-4-yl)-2-(2-methyl-propane-l- sulfonylmethyl)-4-moφholin-4-yl-4-oxo-butyramide; 3-(4-Moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butyrylamino)-4-oxo-pyrrolidine-l -carboxylic acid tert-butyl ester; 4-(4-Moφholin-4-yl-4-oxo-2-benzylsulfonylmemyl-butyrylamino)-3-oxo-azepane-l- carboxylic acid benzyl ester; and acetic acid (2S,3S)-3-(4-moφholin-4-yl-4-oxo-2- benzylsulfonylmethyl-butanoylamino)-4-oxo-azetidin-2-yl ester; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Ν-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 28. A pharmaceutical composition comprising a therapeutically effective amount of a compound of Claim 1 in combination with a pharmaceutically acceptable excipient. 29. A method for treating a disease in an animal in which inhibition of Cathepsin S can prevent, inhibit or ameliorate the pathology and/or symptomology of the disease, which method comprises administering to the animal a therapeutically effective amount of compound of Claim 1 or a N-oxide derivative or individual isomer or mixture of isomers thereof; or a pharmaceutically acceptable salt or solvate of such compounds and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof. 30. The use of a compound of Claim 1 in the manufacture of a medicament for tteatmg a disease in an animal in which Cathepsin S activity contributes to the pathology and/or symptomology of the disease. 31. A process for preparing a compound of Formula I: in which: X 1 is -C(R 1 )(R 2 )X 2 or -X 3 ; X 2 is cyano, -CHO, -C(R 7 )(R 8 )R 5 , -C(R 7 )(R 8 )CF 3 , -C(R 7 )(R 8 )CF 2 CF 2 R 9 -CH=CHS(O) 2 R 5 , -C(R 7 )(R 8 )CF 2 C(O)NR 5 R 6 , -C(R 7 )(R 8 )C(R 7 )(R 8 )NR 5 R 6 , -C(R 7 )(R 8 )C(R 7 )(R 8 )OR 5 , -C(R 7 )(R 8 )CH 2 OR 5 , -C(R 7 )(R 8 )CH 2 N(R 6 )SO 2 R 5 , -C(R 7 )(R 8 )C(R 7 )(R 8 )N(R 6 )(CH 2 ) 2 OR 6 , -C(R 7 )(R 8 )C(R 7 )(R 8 )N(R 6 )(CH 2 ) 2 NR 6 or -C(R 7 )(R 8 )C(R 7 )(R 8 )R 5 ; wherem R 5 is (Cι. 4 )alkyl, (C 6 .ιo)aryl(Co. 6 )alkyl, hetero(C 4 .ιo)a_yl(C 0 - 6 )alkyl, (C . 10 )cycloalkyl(C 0 . 6 )alkyl or hetero(C 4 .ιo)cycloalkyl(C 0 - 6 )alkyl; R 6 is hydrogen or (C^alkyl; R 7 is hydrogen or (Cι. 4 )alkyl and R 8 is hydroxy or R 7 and R 8 together form oxo; R 9 is hydrogen, halo, (Cι, 4 )alkyl, (C 5 .ιo)aryl(Co. 6 )alkyl or hetero(C 5 . 10 )aryl(Co. 6 )alkyl; X 3 represents a group of Formula (a): (a) in which n is 1 or 2, z is 0 or 1, X 5 is selected from NR 10 , S or O, wherem R 10 is hydrogen or (Cι_ 6 )alkyl, and X 6 is O, S or NR 11 , wherein R 11 is selected from hydrogen, (Cι- 6 )alkyl, -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 S(O) 2 R 14 , -R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 C(O)NR 1 R 15 and-X 4 S(O) 2 NR 12 R 15 , in which X 4 is a bond or (Cι_ 6 )alkylene; R 12 at each occurrence independently is hydrogen or (C 1 . 6 )alkyl; R 13 is hydrogen, (Cι_ 6 )alkyl or halo-substituted(C 1 . 6 )alkyl, R 14 is (C 1 . 6 )alkyl or halo-substituted(C 1 . 6 )alkyl and R 15 is (C 3 -ιo)cycloalkyl(Co- 6 )alkyl, hetero(C 3 . 10 )cycloalkyl(Co. 3 )alkyl, (C 6 _ιo)aryl(Co- 6 )alkyl, hetero(C 5 . 10 )aryl(Co- 6 )alkyl, (C .i )bicycloaryl(C 0 . 6 )alkyl or hetero(C 8 .i 2 )bicycloaryl(Co. 6 )alkyl; wherein within X 1 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical R 20 selected from -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR 15 R 12 , -X 4 S(O) 2 NR 15 R 12 , -X 4 NR 12 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 ; and wherein X 1 and R 20 may be substituted further with 1 to 5 radicals independently selected from (Cι_ 6 )alkyl, cyano, halo, halo-substituted(Ci. 4 )alkyl, nitto, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 1 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 wherein X 4 , R 12 , R 13 , R 14 and R 15 are as defined above; R 1 and R" are both fluoro; or R 1 is hydrogen or (Cι_ 6 )alkyl and R 2 is selected from the group consisting of hydrogen, (Cι_ 6 )alkyl, cyano, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 1 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 , -X 4 S(O) 2 R 14 , -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR 15 R 12 , -X 4 S(O) 2 NR 15 R 12 , -X 4 NR 12 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 , wherein X 4 , R 12 , R 13 , R 14 and R 15 are as defined above; or R 1 and R 2 taken together with the carbon atom to which both R 1 and R 2 are attached form (C 3 . 8 )cycloalkylene or hetero(C 3 . 8 )cycloalkylene; wherein R 2 , said cycloalkylene and said heterocycloalkylene may be substituted further with 1 to 3 radicals independently selected from (Cι. 6 )alkyl, cyano, halo, halo-substituted(Ci. 4 )alkyl, nitto, -X 4 NR 12 R 12 , -X 4 NR 1 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 1 C(NR I2 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 , wherein X 4 , R 12 , R 13 and R 14 are as defined above; R 3 and R 4 are independently -C(R 16 )(R 17 )X 7 , wherein R 16 and R 17 are hydrogen, (Cι. 6 )alkyl or fluoro, or R 16 is hydrogen and R 17 is hydroxy and X 7 is selected from -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 , -X 4 S(O) 2 R 14 , -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR 15 R 12 , -X 4 S(O) 2 NR 15 R 12 , -X 4 NR 12 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 , wherein X 4 , R 12 , R 13 , R 14 and R 15 are as defined above; wherein within one of R 3 or R 4 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical R 21 selected from -R 15 , -X 4 OR 15 , -X 4 SR 15 , -X 4 S(O)R 15 , -X 4 S(O) 2 R 15 , -X 4 C(O)R 15 , -X 4 C(O)OR 15 , -X 4 OC(O)R 15 , -X 4 NR 15 R 12 , -X 4 NR 12 C(O)R 15 , -X 4 NR 12 C(O)OR 15 , -X 4 C(O)NR 12 R 15 , -X 4 S(O) 2 NR 15 R 12 , -X 4 NR 12 S(O) 2 R 15 , -X 4 NR 12 C(O)NR 15 R 12 and -X 4 NR 12 C(NR 12 )NR 15 R 12 , wherein X 4 , R 12 and R 15 are as defined above; and wherein each of R 3 , R 4 and R 21 may be substituted further with 1 to 5 radicals independently selected from (Cι_ 6 )alkyl, cyano, halo, halo-substituted(Cι_ )alkyl, nitto, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 12 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and -X 4 S(O) 2 R 14 , wherein X 4 , R 12 , R 13 and R 14 are as defined above; provided that only one bicyclic ring structure is present within each of R 3 or R 4 ; and provided that when X 2 is cyano and X 7 within one of R 3 or R 4 is -X 4 C(O)R 13 or -X 4 C(O)R 15 , wherein X 4 is a bond, then X 7 within the other of R 3 or R 4 is limited to -X 4 SR 15 , -X 4 S(O)R 15 and -X 4 S(O) 2 R 15 , wherem R 15 is (C 6 . 10 )aryl(Cι. 6 )alkyl substituted with 1 to 5 radicals or hetero(C 5 . 1 o)aryl(Co- 6 )alkyl optionally substituted with 1 to 5 radicals, wherein said radicals are independently selected from (Cι_ 6 )alkyl, cyano, halo, halo-substituted -^alkyl, nitro, -X 4 NR 12 R 12 , -X 4 NR 12 C(O)R 12 , -X 4 NR 1 C(O)OR 12 , -X 4 NR 12 C(O)NR 12 R 12 , -X 4 NR 12 C(NR 12 )NR 12 R 12 , -X 4 OR 13 , -X 4 SR 13 , -X 4 C(O)OR 12 , -X 4 C(O)R 13 , -X 4 OC(O)R 13 , -X 4 C(O)NR 12 R 12 , -X 4 S(O) 2 NR 12 R 12 , -X 4 NR 12 S(O) 2 R 13 , -X 4 P(O)(OR 12 )OR 12 , -X 4 OP(O)(OR 12 )OR 12 , -X 4 S(O)R 14 and-X 4 S(O) 2 R 14 , wherein X 4 , R 12 , R 13 and R 14 are as defined above, provided that the radical is not selected from only halo when R 15 is (C 6 -ιo)aryl(Cι- 6 )alkyl; and provided that when X 2 is cyano then X 7 within R 3 and R 4 is not -X 4 C(O)NR 12 R 12 , -X 4 C(O)NR 15 R 12 or -X 4 C(O)NR 18 R 19 , wherein X 4 is a bond and R 18 and R 19 together with the nitrogen atom to which they are attached form hetero(C 3 _ιo)cycloalkyl or hetero(C 5 . 10 )aryl; and the corresponding N-oxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds of formula I and their N-oxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; which process comprises: (A) reacting a compound of Formula 2: 2 with a compound of the formula M ^CR^X 2 , in which X 2 , R 1 , R 2 , R 3 and R 4 are as defined in the Summary of the Invention for Formula I; or (B) reacting a compound of Formula 2 with a compound of the formula NH 2 X 3 , in which X 3 , R 3 and R 4 are as defined in the Summary of the Invention for Formula I; or (C) optionally converting a compound of Formula I into a pharmaceutically acceptable salt; (D) optionally converting a salt form of a compound of Formula I to non-salt form; (E) optionally converting an unoxidized form of a compound of Formula I into a pharmaceutically acceptable N-oxide; (F) optionally converting an N-oxide form of a compound of Formula I its unoxidized form; (G) optionally resolving an individual isomer of a compound of Formula I from a mixture of isomers; (H) optionally converting a non-derivatized compound of Formula I into a pharmaceutically prodrug derivative; and (I) optionally converting a prodrug derivative of a compound of Formula I to its non-derivatized form.

Inventors: ALDOUS DAVID, GRAUPE MICHAEL, HALLEY FRANK, LAI JUSTINE, LI JIAYAO, LINK JOHN, PATTERSON JOHN, PICKETT STEPHEN D, THURAIRATNAM SUKANTHINI, TIMM ANDREAS, ALDOUS, DAVID, GRAUPE, MICHAEL, HALLEY, FRANK, LAI, JUSTINE, LI, JIAYAO, LINK, JOHN, PATTERSON, JOHN, PICKETT, STEPHEN, D., THURAIRATNAM, SUKANTHINI, TIMM, ANDREAS
Applicants: ALDOUS DAVID, CELERA AN APPLERA CORP BUSINES, GRAUPE MICHAEL, HALLEY FRANK, LAI JUSTINE, LI JIAYAO, LINK JOHN, PATTERSON JOHN, PICKETT STEPHEN D, THURAIRATNAM SUKANTHINI, TIMM ANDREAS, ALDOUS, DAVID, CELERA, AN APPLERA CORPORATION BUSINESS, GRAUPE, MICHAEL, HALLEY, FRANK, LAI, JUSTINE, LI, JIAYAO, LINK, JOHN, PATTERSON, JOHN, PICKETT, STEPHEN, D., THURAIRATNAM, SUKANTHINI, TIMM, ANDREAS
Application year: 2001
Main classification: C12N
IPC codes: A61K31, A61P3, A61P9, A61P11, A61P17, A61P19, A61P21, A61P25, A61P29, A61P37, A61P43, C07C317, C07C323, C07D205, C07D207, C07D223, C07D263, C07D271, C07D277, C07D285, C07D295, C07D413, C07D498