1,4 SUBSTITUTED PIPERIDINYL NMDA/NR2B ANTAGONISTS

Abstract: Novel piperidinyl compounds substituted in the 1- and 4-positions are effective as NMDA NR2B antagonists useful for relieving pain.

Description: TITLE OF THE INVENTION 1,4 SUBSTITUTED PIPERIDINYL NMDA/NR2B ANTAGONISTS BACKGROUND OF THE INVENTION Field of the Invention This invention relates to novel 1,4 substituted pipeπdmes . In particular, this invention relates to pipeπdines substituted in the 1- and 4-posιtιons, through a bπdge, with l) optionally substituted 2-benzιmιdazoles, 2-ιndoles, 2- quinazo nes, or 2-ιmιdazopyπ dines; or n) phenyl or substituted phenyl that are effective as NMDA NR2B antagonists useful for relieving pain. Ions such as glutamate play a key role in processes related to chronic pain and pain-associated neurotoxicity - pπmaπly by acting through N-methyl-D- aspartate ("NMDA") receptors. Thus, inhibition of such action - by employing ion channel antagonists, particularly NMDA antagonists - can be beneficial in the treatment and control of pain. Known NMDA antagonists include ketamine, dextromophan, and 3-(2- carboxypιperazιn-4-yl)-propyl-l-phosphonιc acid ("CPP"). Although these compounds have been reported (J.D.Kπstensen, et al., Pain, 51:249-253 (1992), K.Eide, et al., Pain, 61.221-228 (1995); D .Knox, et al., Anaesth Intensive Care 23:620-622 (1995); and M.B.Max, et al., Clin.Neuropharmacol. 18:360-368 (1995)) to produce symptomatic relief in a number of neuropathies including postherpetic neuralgia, central pain from spinal cord injury, and phantom limb pain, widespread use of these compounds is precluded by their undesirable side effects. Such side effects at analgesic doses include psychotormmetic effects such as dizziness, headache, hallucinations, dysphoπa, and disturbances of cognitive and motor function. Additionally, more severe hallucinations, sedation, and ataxia are produced at doses only marginally higher than analgesic doses. Thus, it would be desirable to provide novel NMDA antagonists that are absent of undesirable side effects or that produce fewer and/or milder side effects. NMDA receptors are heteromeπc assemblies of subumts, of which two major subunit families designated NRl and NR2 have been cloned Without being bound by theory, it is generally believed that the vaπous functional NMDA receptors in the mammalian central nervous system ("CNS") are only formed by combinations of NRl and NR2 subunits, which respectively express glycine and glutamate recognition sites. The NR2 subunit family is m turn divided into four individual subunit types: NR2A, NR2B, NR2C, and NR2D. I Ishn, et al., /. Biol Chem., 268.2836-2843 (1993), A. Wenel, et al., Neural Report, 7:45-48 (1995), and D.J.Lauπe et al., Mol. Brain Res., 5_1.23-32 (1997) descπbe how the vaπous resulting combinations produce a vaπety of NMDA receptors diffeπng in physiological and pharmacological properties such as ion gating properties, magnesium sensitivity, pharmacological profile, as well as anatomical distribution. For example, while NRl is found throughout the brain, NR2 subunits are differentially distπbuted. In particular, it is believed that the distribution map for NR2B lowers the probability of side effects while producing pain relief. For example, S.Boyce, et al., Neuropharmacology, 38:611-623(1999) descπbes the effect of selective NMDA NR2B antagonists on pain with reduced side-effects. Thus, it would be desirable to provide novel NMDA antagonists that target the NR2B receptor. Phenol compounds descπbed as NMDA antagonists are descπbed in U.S. Patent Nos. 5,306,723 and 5,436,255, and in International Patent Publications WO91/17156, WO92/19502, WO93/02052, WO94/29571, WO95/28057, WO96/37226, and EP 04422506. Benzyl pipeπdine substituted with phenols or lmidazoles are descπbed in Z.-L. Zhou, et al , J. Medicinal Chemistry, 42:2993- 3000(1999); T.F.Gregory, et al., Poster #94, 218 th National Meeting Ameπcan Chemical Society, New Orleans, Louisiana, August 22-26, 1999 Other NMDA NR2B selective compounds are descπbed in European Patent Publication EP 787493 and British J.Pharmacol., 123:463(1998). However, there continues to be a need for novel NMDA antagonists that target the NR2B receptor. International Patent Publication WO94/21615 descπbes benzimidazole-pipeπdine compounds utilized as dopamme D4 antagonists. SUMMARY OF THE INVENTION The present invention relates to novel pipeπdines substituted m the 1- and 4-posιtιons, through a bπdge, with I) optionally substituted 2-benzιmιdazoles, 2- mdoles, 2-qumazolmes, or 2-ιmιdazopyπdmes; or n) phenyl or substituted phenyl The present mvention also forms pharmaceutical compositions utilizing the compounds Further, this invention includes novel methods to treat pain by utilizing the compounds. DETAILED DESCRIPTION OF THE INVENTION In one aspect, the compounds of this invention are represented by Formula (I): (I) or pharmaceutically acceptable salts thereof, wherein Ri is I) 2-benzιmιdazole, 2-ιmιdazopyπdme, 2-ιndole, puπne, or 2- qumazolme, each optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cι -C4alkyl, tπfluoromethyl, Cj- C4alkylsulfonamιde, hydroxy, or carboxy; or n) phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cι -C4alkyl, tπfluoromethyl, Ci-C4alkylsulfonamιde, hydroxy, or carboxy; R2 is a) 2-benzιmιdazole, 2-ιmιdazopyπdme, 2-ιndole, puπne, or 2- quinazohne, each optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Ci-C4alkyl, tπfluoromethyl, C]- C4alkylsulfonamιde, hydroxy, or carboxy; or b) phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cι -C4alkyl, tπfluoromethyl, Cι -C4alkylsulfonamιde, hydroxy, or carboxy; When Ri is I, then R2 is b; when Ri is n, then R2 is a; When Ri or R2 is 2-benzιmιdazole, respective Li or L2 is not Ci - C2alkyl, except when Ri or R2 is hydroxy-substituted 2-benzιmιdazole, respective Li or L2 includes C 1 -C2alkyl Li and L2 are independently Cι-C4alkyl, Cj-C4alkenyl, Ci - C4alkynyl, Cι-C4alkoxy, amιnoCι-C4alkyl, hydroxyCι-C4alkyl, carbonyl, cycloC3- Cβalkyl or ammocarbonyl; and optionally substituted at any of the 2, 3, 5, or 6 positions independently with X, wherein X is hydroxy, amino, Cι-C4alkylamιno, dι(Cι-C4)alkylamιno, Ci - C4alkyl, ester, carbamate, carbonate, or ether. In an embodiment of this invention the compound is represented by Formula (I) or a pharmaceutically acceptable salt thereof, wherein Rl is 2-ιmιdazopyπdιne, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cj-C4alkyl, tπfluoromethyl, Cι -C4alkylsulfonamιde, hydroxy, or carboxy; R2 is phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cj-C4alkyl, tπfluoromethyl, Ci-C4alkylsulfonamιde, hydroxy, or carboxy; Lj and L2 are independently Cι-C4alkyl, Cι-C4alkenyl, C]- C4alkynyl, Ci-C4alkoxy, amιnoCι -C4alkyl, hydroxyCj-C4alkyl, carbonyl, cycloC3- Cβalkyl or aminocarbonyl; and optionally substituted at any of the 2, 3, 5, or 6 positions independently with X, wherein X is hydroxy, amino, Ci-C4alkylamιno, dι(Ci-C4)alkylamιno, Cj- C4alkyl, ester, carbamate, carbonate, or ether. In another embodiment of this invention the compound is represented by Formula (I) or a pharmaceutically acceptable salt thereof, wherein Rj is puπne, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cj -C4alkyl, tπfluoromethyl, Cj-C4alkylsulfonamιde, hydroxy, or carboxy, R2 is phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cι-C4alkyl, tπfluoromethyl, Cι-C4alkylsulfonamιde, hydroxy, or carboxy, Lj and L2 are independently Cι -C4alkyl, Cj-C4alkenyl, Ci- C4alkynyl, Cj-C4alkoxy, ammoCι -C4alkyl, hydroxyCι-C4alkyl, carbonyl, cycloC3- Cgalkyl or aminocarbonyl; and optionally substituted at any of the 2, 3, 5, or 6 positions independently with X, wherein X is hydroxy, amino, Ci-C4alkylam.no, dι(Ci-C4)alkylamιno, Cj- C4alkyl, ester, carbamate, carbonate, or ether. In still another embodiment of this invention the compound is represented by Formula (I) or a pharmaceutically acceptable salt thereof, wherein Rj is 2-benzιmιdazole, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cj-C4alkyl, tπfluoromethyl, Cι-C4alkylsulfonamιde, hydroxy, or carboxy; R2 is phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cι-C4alkyl, tπfluoromethyl, Cι-C4alkylsulfonamιde, hydroxy, or carboxy; Lj IS not Cj-C2alkyl, except when R\ is hydroxy-substituted 2- benzimidazole, Li includes Cj-C2alkyl; Lj and L2 are independently Ci-C4alkyl, Cι-C4alkenyl, Ci- C4alkynyl, Ci-C4alkoxy, ammoCi-C4alkyl, hydroxyCj-C4alkyl, carbonyl, cycloC3- C6alkyl or aminocarbonyl, and optionally substituted at any of the 2, 3, 5, or 6 positions independently with X, wherein X is hydroxy, ammo, Cι-C4alkylamιno, dι(Cι-C4)alkylamιno, C{- C4alkyl, ester, carbamate, carbonate, or ether. As used herein, "alkyl" as well as other groups having the prefix "alk" such as, for example, alkoxy, alkanoyl, alkenyl, alkynyl and the like, means carbon chains which may be linear or branched or combinations thereof. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, sec- and tert-butyl, pentyl, hexyl, heptyl and the like. "Alkenyl", "alkynyl" and other like terms include carbon chains containing at least one unsaturated C-C bond. The term "cycloalkyl" means carbocycles containing no heteroatoms, and includes mono-, bi- and tπcyclic saturated carbocycles, as well as fused πng systems. Such fused πng systems can include one πng that is partially or fully unsaturated such as a benzene πng to form fused πng systems such as benzofused carbocycles. Cycloalkyl includes such fused πng systems as spirofused πng systems. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, decahydronaphthalene, adamantane, mdanyl, mdenyl, fluorenyl, 1,2,3,4- tetrahydronaphalene and the like. Similarly, "cycloalkenyl" means carbocycles containing no heteroatoms and at least one non-aromatic C-C double bond, and include mono-, bi- and tπcychc partially saturated carbocycles, as well as benzofused cycloalkenes. Examples of cycloalkenyl include cyclohexenyl, indenyl, and the like Unless otherwise stated, the terms "carbonyl" and "aminocarbonyl" include short C]-C2 termini. The terms include, for example, -CH2CONH-, -CH2CO-, -C2H4CONHCH2-, and -CH2COC2H4- Unless otherwise stated, the term "carbamate" is used to include -OCOOCi-C4alkyl, -NHCOOCι-C4alkyl, and -OCONHCi-C4alkyl The term "halogen" includes fluoπne, chloπne, bromine and iodine atoms. The term "SEM" is used to descπbe -CH2-O-CH2CH2-Sι(CH3)3 The term "Co" means that the carbon is not present. Thus, "C0-C5" means that there are from none to five carbons present - that is, five, four, three, two, one, or no carbons present. The term "optionally substituted" is intended to include both substituted and unsubstituted. Thus, for example, optionally substituted aryl could represent a pentafluorophenyl or a phenyl πng Compounds descπbed herein contain one or more asymmetπc centers and may thus give πse to diastereomers and optical isomers. The present invention includes all such possible diastereomers as well as their racemic mixtures, their substantially pure resolved enantiomers, all possible geometπc isomers, and pharmaceutically acceptable salts thereof. The above Formula I is shown without a definitive stereochemistry at certain positions. The present invention includes all stereoisomers of Formula I and pharmaceutically acceptable salts thereof. Further, mixtures of stereoisomers as well as isolated specific stereoisomers are also included. Duπng the course of the synthetic procedures used to prepare such compounds, or in using racemization or epimeπzation procedures known to those skilled in the art, the products of such procedures can be a mixture of stereoisomers. The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases or acids. When the compound of the present invention is acidic, its corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic bases, including inorganic bases and organic bases. Salts deπved from such inorganic bases include aluminum, ammonium, calcium, copper (IC and ous), feme, ferrous, lithium, magnesium, manganese (ic and ous), potassium, sodium, zinc and the like salts. Particularly preferred are the ammonium, calcium, magnesium, potassium and sodium salts. Salts deπved from pharmaceutically acceptable organic non-toxic bases include salts of pπmary, secondary, and tertiary ammes, as well as cyclic amines and substituted amines such as naturally occurπng and synthesized substituted amines Other pharmaceutically acceptable organic non-toxic bases from which salts can be formed include ion exchange resms such as, for example, arginine, betaine, caffeine, choline, N,N -dibenzylethylenediamine, diethylamme, 2-dιethylamιnoethanol, 2- dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethylmorphohne, N- ethylpipeπdine, glucamine, glucosamme, histidine, hydrabamine, isopropylamine, lysme, methylglucamine, morpholme, piperazine, pipeπdine, polyam e resins, procaine, puπnes, theobromine, tπethylamme, tπmethylamine, tπpropylamine, trometham e and the like. When the compound of the present invention is basic, its corresponding salt can be conveniently prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. Such acids include, for example, acetic, benzenesulfonic, benzoic, camphorsulfonic, citπc, ethanesulfonic, fumaπc, gluconic, glutamic, hydrobromic, hydrochloπc, lsethionic, lactic, maleic, malic, mandehc, methanesulfonic, mucic, nitπc, pamoic, pantothenic, phosphoπc, succmic, sulfuπc, tartaπc, p-toluenesulfonic acid and the like. Particularly preferred are citπc, hydrobromic, hydrochloπc, maleic, phosphoπc, sulfuπc, and tartaπc acids. The pharmaceutical compositions of the present invention compnse a compound represented by Formula I (or pharmaceutically acceptable salts thereof) as an active ingredient, a pharmaceutically acceptable earner and optionally other therapeutic ingredients or adjuvants. The compositions include compositions suitable for oral, rectal, topical, and parenteral (including subcutaneous, intramuscular, and intravenous) administration, although the most suitable route in any given case will depend on the particular host, and nature and seventy of the conditions for which the active ingredient is being administered. The pharmaceutical compositions may be conveniently presented in unit dosage form and prepared by any of the methods well known the art of pharmacy. In practice, the compounds represented by Formula I, or pharmaceutically acceptable salts thereof, of this invention can be combined as the active ingredient intimate admixture with a pharmaceutical earner according to conventional pharmaceutical compounding techniques. The earner may take a wide vaπety of forms depending on the form of preparation desired for administration, e.g., oral or parenteral (including intravenous). Thus, the pharmaceutical compositions of the present invention can be presented as discrete units suitable for oral administration such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient. Further, the compositions can be presented as a powder, as granules, as a solution, as a suspension in an aqueous liquid, as a non-aqueous liquid, as an oil-in-water emulsion or as a water-m-oil liquid emulsion In addition to the common dosage forms set out above, the compound represented by Formula I, or pharmaceutically acceptable salts thereof, may also be administered by controlled release means and/or delivery devices The compositions may be prepared by any of the methods of pharmacy In general, such methods include a step of bnngmg into association the active ingredient with the earner that constitutes one or more necessary ingredients In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid earners or finely divided solid earners or both The product can then be conveniently shaped into the desired presentation Thus, the pharmaceutical compositions of this invention may include a pharmaceutically acceptable earner and a compound or a pharmaceutically acceptable salt of Formula I The compounds of Formula I, or pharmaceutically acceptable salts thereof, can also be included in pharmaceutical compositions in combination with one or more other therapeutically active compounds The pharmaceutical earner employed can be, for example, a solid, liquid, or gas Examples of solid earners include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, acacia, magnesium stearate, and steanc acid Examples of liquid earners are sugar syrup, peanut oil, olive oil, and water Examples of gaseous earners include carbon dioxide and nitrogen In prepaπng the compositions for oral dosage form, any convenient pharmaceutical media may be employed For example, water, glycols, oils, alcohols, flavonng agents, preservatives, coloπng agents and the like may be used to form oral liquid preparations such as suspensions, elixirs and solutions, while earners such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubncants, binders, disintegrating agents, and the like may be used to form oral solid preparations such as powders, capsules and tablets Because of their ease of administration, tablets and capsules are the preferred oral dosage units whereby solid pharmaceutical earners are employed Optionally, tablets may be coated by standard aqueous or nonaqueous techniques A tablet containing the composition of this invention may be prepared by compression or molding, optionally with one or more accessory ingredients or adjuvants Compressed tablets may be prepared by compressing, in a suitable machine, the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubπcant, inert diluent, surface active or dispersing agent. Molded tablets may be made by molding in a suitable machine, a mixture of the powdered compound moistened with an inert liquid diluent Each tablet preferably contains from about lmg to about 500mg of the active ingredient and each cachet or capsule preferably containing from about 1 to about 500mg of the active ingredient Pharmaceutical compositions of the present invention suitable for parenteral administration may be prepared as solutions or suspensions of the active compounds in water. A suitable surfactant can be included such as, for example, hydroxypropylcellulose Dispersions can also be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof in oils. Further, a preservative can be included to prevent the detπmental growth of microorganisms Pharmaceutical compositions of the present invention suitable for injectable use include stenle aqueous solutions or dispersions. Furthermore, the compositions can be in the form of stenle powders for the extemporaneous preparation of such stenle injectable solutions or dispersions. In all cases, the final injectable form must be stenle and must be effectively fluid for easy syπngabihty. The pharmaceutical compositions must be stable under the conditions of manufacture and storage; thus, preferably should be preserved against the contaminating action of microorganisms such as bactena and fungi. The earner can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g. glycerol, propylene glycol and liquid polyethylene glycol), vegetable oils, and suitable mixtures thereof. Pharmaceutical compositions of the present invention can be in a form suitable for topical use such as, for example, an aerosol, cream, ointment, lotion, dusting powder, or the like. Further, the compositions can be m a form suitable for use in transdermal devices. These formulations may be prepared, utilizing a compound represented by Formula I of this invention, or pharmaceutically acceptable salts thereof, via conventional processing methods. As an example, a cream or ointment is prepared by mixing hydrophilic mateπal and water, together with about 5 wt% to about 10 wt of the compound, to produce a cream or ointment having a desired consistency. Pharmaceutical compositions of this invention can be in a form suitable for rectal administration wherein the earner is a solid. It is preferable that the mixture forms unit dose suppositoπes. Suitable earners include cocoa butter and other matenals commonly used m the art. The suppositones may be conveniently formed by first admixing the composition with the softened or melted carner(s) followed by chilling and shaping in moulds. In addition to the aforementioned earner ingredients, the pharmaceutical formulations descnbed above may include, as appropnate, one or more additional earner ingredients such as diluents, buffers, flavonng agents, binders, surface-active agents, thickeners, lubπcants, preservatives (including anti-oxidants) and the like. Furthermore, other adjuvants can be included to render the formulation isotonic with the blood of the intended recipient Compositions containing a compound descπbed by Formula I, or pharmaceutically acceptable salts thereof, may also be prepared in powder or liquid concentrate form Expenmental Protocols Assessing the Activity of Selected Compounds to Inhibit NR1A/2B NMDA Receptor Activation (FLIPR Assay) The activity of selected compounds to inhibit NR1A/2B NMDA receptor activation measured as NR1A/2B receptor-mediated Ca 2+ influx is assessed by the following procedure: NRl A/2B receptor transfected L(tk) cells are plated in 96-well format at 3 x 10 cells per plate and grown for one - two days in normal growth media (Dulbeccos MEM with Na pyruvate, 4500 mgglucose, pen/strep, glutamine, 10% FCS and 0.5mg/ml genetic ). NR1A/2B -expression in these cells is induced by the addition of 4nM dexamethasone in the presence of 500μM ketamine for 16 - 24 hours. After receptor induction cells are washed using a Labsystem Cellwasher two times with assay buffer (Hanks balanced salt solution (HBSS-Mg ++ free) containing 20mM HEPES, 0.1% BSA, 2mM CaCl 2 and 250μM probenecid). The cells of each 96 well cell plate are loaded with the Ca ++ sensitive dye Fluo-3 (Molecular Probes, Inc.) at 4μM in assay buffer containing 0.5% FBS, and 0.04% pluronic F-127 (Molecular Probes, Inc.) for lh at 37 °C avoiding light. The cells are then washed with the Cellwasher four times with assay buffer leaving them in lOOμl buffer. Test compounds in solution are pipetted by FLIPR (Fluorometπc Imaging Plate Reader) into each test well for a 2mιn pretreatment. Duπng this time the fluorescence intensity is recorded (excitation at 488nm and emission at 530nm). The glutamate/glycine 50μl agonist solution (final concentration l μM/lμM) is then added by FLIPR into each well already containing 150μl of buffer (containing the test compound or vehicle) and the fluorescence is continuously monitored for 10mm The endpoint fluorescence values are used to determine an IC 50 value companng the agonist-stimulated signal for the vehicle alone sample and that for the cells incubated with each concentration of test compound Determining the Apparent Dissociation Constant (Ki) of Compounds for Human NR1A/NR2B Receptors (Binding Assay): The radioligand binding assay is performed at room temperature in 96-well microtiter plates with a final assay volume of l.OmL in 20mM Hepes buffer (pH 7.4) containing 150mM NaCl. Solutions of test compounds were prepared in DMSO and serially diluted with DMSO to yield 20μL of each of 10 solutions differing by 3-fold in concentration. Non-specific binding (NSB) using hot AMD-1 (lOμM final concentration) and total binding (TB) by using DMSO (2% final concentration). A solution of NR1A/NR2B receptors (40pM final concentration) and tπtiated AMD-2 (InM final concentration) were added to the test compounds. After 3h of incubation at room temperature, samples are filtered through Packard GF/B filters (presoaked in 0.05% PEI, polyethyleninme Sigma P-3143) and washed 10 times with lmL of cold 20mM Hepes buffer per wash. After vacuum drying of the filter plates, 40μL of Packard Mιcroscmt-20 was added and bound radioactivity determined in a Packard TopCount. The apparent dissociation constant (Ki), the maximum percentage inhibition (%Imax tne minimum percentage inhibition (%Imιn) and the hill slope (nH) were determined by a non-linear least squares fitting the bound CPM data to Equation #1 below Equatιon#l. (SB) (%I max - %I mιn ) CPM Bound = + NSB + (SB) (1 %Imax) (1 + ( [Drug] / (Ki [L-844,345]/K D ) ) nH ) where, K D IS the apparent dissociation constant for the radioligand for the receptor as determined by hot saturation and SB is the specifically bound CPM determined from the difference of TB and NSB. AMD-1 AMD-2 Compounds AMD-1 and AMD-2 can be synthesized in accordance with the following general reaction schemes. SCHEME 1 R 3 H la In accordance with scheme 1, hydrogen chlonde is bubbled through a solution of the appropnately substituted benzomtnle 1 in methanol at room temperature. The volatiles are removed under reduced pressure and the resulting residue is tπturated with ether and filtered to yield the desired imidate 2. Imidate 2 is dissolved in methanol at ambient temperature, treated with am e 3 at ambient temperature and stirred under argon. The volatiles are removed under reduced pressure and the residue punfied by preparative HPLC or tπturation with ether to afford amidine la. SCHEME 2 R 2 -C 0 6 alkyl-NR 3 H HCl e AI -*- Me 2 CI AI-NH 2 -C 0 6 alkyl -R 2 3a 6 la In accordance with scheme 2, at room temperature under argon, amine 3a is dissolved in ether and was treated with 1-M hydrogen chloπde in ether (1 equiv.) in a single portion. The resulting precipitate is stirred vigorously for 10 minutes. The volatiles are removed under reduced pressure. The residue is suspended in toluene, cooled to 0°C under argon, treated with 2.0-M tnmethylaluminum (1.05 equiv.) in a dropwise manner, and stirred for 45 minutes at room temperature to afford intermediate 6 (not isolated) Compound 6 is added to a solution of nitπle 1 m toluene. The reaction is heated to 80°C without stirπng in a sealed tube for 18h, cooled to ambient temperature, poured onto a silica gel column and eluted with methanol/dichloromethane to give the amidine 4. Preparation of [ 125 I]AMD-1 ]AMD-1 Tntiated AMD-1 was prepared by the following procedure: A mixture of AMD-1, hydrochloπde salt, (5mg, 0.012mmol) in dioxane (0.2mL) containing tnethylamine (4μL) was treated with hexamethylditin (5μL), a catalytic amount of palladium catalyst and heated at 100°C for 45 minutes. The reaction was cooled to room temperature, filtered through a glass wool plug, πnsed with methanol and concentrated in vacuo to give 10.7mg of a brown oil The oil was dissolved in methylene chlonde and passed through a small silica column eluting with methylene chlonde followed by 5% methanol/methylene chlonde Fractions containing the tnmethylstannane (Rf 0.26 in 10% methanol/methylene chloπde) were pooled and concentrated in vacuo to give 4.5mg of the tnmethylstannane as a clear colorless oil. This matenal was further puπfied by HPLC (C18 Econosil, 10x250mm, 20 minute linear gradient, 30% MeCN:70% H 2 O (0.1% TFA) to 90% MeCN, 3mIJmιn, 254nm, retention time 15 minutes) to give 3mg of the tnmethylstannane. A Na 123 I shipping vial (lOmCi, Amersham) was charged with a stir bar, an iodobead, 50μL of methanol and stirred five minutes at room temperature A solution of the tnmethylstannane (O.lmg) in 50μL of methanol containing 5μL of tπfluoroacetic acid was added and the reaction was stirred for five minutes. The reaction was quenched with 50μL of ammonium hydroxide and punfied by HPLC (C18 Vydac protein and peptide column, 4.6 x 250 mm, 20 minute linear gradient, 30% MeCN:70% H 2 O (0.1% TFA) to 90% MeCN, lmL/min, retention time 1 lmmutes). Fractions containing the radioactive product were pooled and concentrated in vacuo to give 989μCι of [ I] AMD-1 with a specific activity of 898Cι/mmol as measured by UV absorbance at 272nm. Synthesis of Tritiated AMD-2 Tπtiated AMD-2 was prepared by the following procedure: The phenol of AMD-2 (2mg, 0 008mmol) dissolved in dimethylformamide (0.6mL) and potasium carbonate (1.2mg) for lhr. High specific activity tπtiated methyl iodide (50mCι, 0.0006mmol, in toluene lmL, Amencan Radiolabeled Chemicals) was added at room temperature and stirred for 2 hours The reaction mixture was filtered using a Whatman PTFE 0.45μm synngeless filter device to remove any msoluable potassium carbonate, washed with Abs. ethanol (2mL, Pharmco), and the combined filtrates were concentrated to dryness at room temperature using a rotary evaporator; this also removed any unreacted tπtiated methyl iodide The residue was puπfied by HPLC chromatography on a Phenomenx Luna C8 semi-prep column ( Luna 5 micro C8(2), 250x10.0 mm) using a gradient system of 20/80 acetonitnle/water with 0.1% tπfluoroacetic acid to 100% acetronitnle with 0.1% tnfluoroacetic acid m 20mιn. Total activity of the product was 8mCι. Further punfication was effected by absorption onto a Waters C-18 Sep-pak column (Waters Sep-Pak PLUS C18) and elution with water followed by absolute ethanol The product was diluted with absolute ethanol (lOmL) before submission for final analysis. The compounds of this invention exhibit less than 50μM in the FLIBR and binding assays. Thus, the compounds and pharmaceutical compositions of this invention have been found to exhibit biological activity as NMDA NR2B antagonists. Accordingly, another aspect of the invention is the treatment of pain, migraine, depression, anxiety, schizophrenia, Parkinson's disease, or stroke - maladies that are amenable to amelioration through inhibition of NMDA NR2B receptors - by the administration of an effective amount of the compounds of this invention. The following examples are provided to more fully illustrate the present invention, and are not to be construed as limiting the scope of the claims in any manner. EXAMPLES The compounds of this invention can be prepared by procedures similar to Scheme 1 shown below but modified by the utilization of other reactants in place of l-SEM-benzιmιdole-2-carboxaldehyde. Scheme 1 In Scheme 1 above, in place of the l-SEM-benzιmιdole-2- carboxaldehyde SEM any of the following aldehydes or ketones can be used to prepare the compounds of this invention: KNOWN EXAMPLE 2-(4-BenzyI-piperidin-l-ylmethyl)-lH-benzimidazole Example 1 was prepared by the following procedure. Step 1: l-(2-Trimethylsilylethoxymethyl)-lH-benzoimidazole: A mixture of KH, from 7g of 30% oil dispersion, and 5g of benzimidazole in lOOmL of THF was stirred under nitrogen at room temperature for 18h. To the stirred suspension was added 7 g of 2-tnmethylsιlylethoxymethyl chloπde and the mixture kept at room temperature for 24h, cooled in an ice bath, cautiously quenched with 50mL of water, and extracted into ether. The combined ether extracts were dned over magnesium sulfate and concentrated. Low pressure chromatography over silica gel eluting with a gradient of 3:1 ethyl acetate:hexane to 100% ethyl acetate gave 9.5g of 1-SEM-benzιmιdazole as a colorless oil. Step 2: l-(2-Trimethylsilylethoxymethyl)-lH-benzoimidazole-2-carbaldehyde: To a solution of 40mmole of lithium dnsopropylamide in lOOmL of THF cooled to -78°C was added 5g of 1-SEM-benzιmιdazole in 50mL of THF. After 1.5h at or below -70°C, the red solution was quenched by rapid addition of 6mL of methyl formate. After warming to room temperature over 30mιn, 50mL of water and 200mL of ethyl acetate were added. The organic layer was separated and dned over magnesium sulfate then concentrated under reduced pressure to 5 3g of a thick oil that solidified in the freezer. Step 3: 2-(4-Benzyl-piperidin-l-ylmethyl)-lH-benzimidazoIe: A mixture of 0.5g of 4-benzyl-pιpendme, 0.5g of l-(2- tπmethylsιlylethoxymethyl)-lH-benzoιmιdazole-2-carbaldehyde, 5mL of 1,2- dichloroethane and 0.5g of sodium tπacetoxyborohydnde was stirred at room temperature for 48h. The reaction mixture was diluted with 50mL chloroform and lOmL saturated aqueous Na2CO3 and the layers separated The aqueous layer was extracted with 2X25mL of chloroform and the combined organic layers dned over magnesium sulfate and concentrated under reduced pressure The crude SEM ether was heated to reflux in 50mL of ethanol containing 5mL of 3N HCl for 2h, cooled, concentrated and partitioned between lOmL of saturated aqueous sodium carbonate and 3X25mL of chloroform. The chloroform extracts were dned over magnesium sulfate and concentrated. Punfication by chromatography eluting with 90:10 CHCl3"MeOH gave 0.8g of 2-[4-benzyl-pιpeπdιn-l-ylmethyl]-lH-benzιmιdazole: MS (m+1) = ; *H NMR (400MHz, CDC1 3 ) EXAMPLE 1 2-(4-Benzyl-piperidin-l-ylmethyl)-imidazo[4,5-b]pyridine Example 1 was prepared in a similar manner to the Known Example above, but substituting 3H-ιmιdazo[4,5-b]pyπdιne for benzimidazole m Step 1. Purification by chromatography eluting with 90: 10 CHCl3:MeOH gave 2-(4-benzyl- pιpeπdιn-l-ylmethyl)-ιmιdazo[4,5-b]pyπdιne: MS (m+1) = 307.4, *H NMR (400MHz, CDC1 3 ) 9.75 (br, IH), 8.4 (d, IH), 7.95 (d, IH), 7.3-7.1 (m, 5H), 3.9 (s, 2H), 2.9 (d, 2H), 2.6 (d, 2H), 2.2 (dd, 2H), 1.7 (d, 2H), 1.7 (m, IH), 1 4 (dd, 2H). EXAMPLE 2 8-(4-Benzy 1-piperidin- 1 -ylmethyl)-purine Example 2 was prepared in a similar manner to the Known Example above, but substituting puπne for benzimidazole in Step 1. Punfication by chromatography eluting with 90: 10: 1 CHCl3:MeOH:NH4OH gave 8-(4-benzyl- pιpendιn-l-ylmethyl)-punne: MS (m+1) = 308.4; *H NMR (400MHz, CDCI3) 9.05 (s, IH), 9.0 (s, IH), 7.3-7.1 (m, 5H), 3.9 (s, 2H), 2.9 (d, 2H), 2.6 (d, 2H), 2.2 (dd, 2H), 1.7 (d, 2H), 1.7 (m, IH), 1.4 (dd, 2H). EXAMPLE 3 2-(4-Benzyl-piperidin-l-ylmethyl)-imidazo[4,5-c]pyridine Example 3 was prepared m a similar manner to the Known Example above, but substituting 3H-ιmιdazo[4,5-b]pyπdme for benzimidazole in Step 1. Punfication by chromatography eluting with 90: 10: 1 CHCl3:MeOH:NH4OH gave 2- (4-benzyl-pιpeπdιn-l-ylmethyl)-ιmιdazo[4,5-c]pyndme. MS (m+1) = 307.4; ^H NMR (400MHz, CDCI 3 ) 9.75 (br, IH), 8.4 (d, IH), 7.95 (d, IH), 7.3-7.1 (m, 6H), 3.90 (s, 2H), 2.90 (d, 2H), 2.6 (d, 2H), 2.2 (dd, 2H), 1 7 (d, 2H), 1 7 (m, IH), 1.4 (dd, 2H). EXAMPLE 4 2-[3-(4-Benzyl-piperidin-l-yl)-propyl]-lH-benzimidazole Example 4 was prepared by the following procedure Step 1: 3-(lH-Benzimidazol-2-yl)-propan-l-ol: A mixture of 5.4g of 1,2-phenylenedιamme and 4.5g of dihydro-furan- 2-one in 50mL of 4N hydrochlonc acid was heated to reflux for 20h, 1 teaspoon of decoloπzmg carbon added, and after another 15mm reflux, filtered hot. The filtrate was concentrated under reduced pressure to near dryness, the residue made basic (pH = 8) with saturated sodium bicarbonate and extracted into 3X80mL of ether. The combined extracts were dned over magnesium sulfate and concentrated under reduced pressure. After drying under vacuum, 8.4g of 3-(lH-benzιmιdazol-2-yl)-propan-l-ol was obtained as a solid. Step 2: 3-[2-(3-Hydroxy-propyl)-benzimidazoI-l-yl]-propionitrile: To a stirred solution of 3.8g of 3-(lH-benzιmιdazol-2-yl)-propan-l-ol and 4g dihydropyran in 500mL of THF was added p-toluenesulfonic acid monohydrate until the pH was about 3 (indicator paper) After stirnng overnight, an additional 2mL of dihydropyran was added After 2 additional hours, the conversion was complete. The mixture was concentrated under reduced pressure and partitioned between 250mL of IN NaOH and 2X250mL of ether. After drying over magnesium sulfate the combined extracts were concentrated to dryness. To a solution of the resulting crude oily 2-[3-(tetrahydro-pyran-2- yloxy)-propyl]-lH-benzιmιdazole (14g) in 250mL of acetonitπle was added 5 L of acrylonitπle, 2 drops of IM tetrabutylammonium fluonde in THF and 1 drop ION NaOH After heating to 85°C for 16h, conversion was complete (TLC elution with 90:10 methylene chloπde:methanol). After concentration under reduced pressure, the residue was partitioned between 2X200mL of ethyl acetate and 200mL of water The combined extracts were dned over magnesium sulfate and concentrated under reduced pressure.. The crude 3-{2-[3-(tetrahydro-pyran-2-yloxy)-propyl]-benzιmιdazol-l- yl}-propιonιtπle was stirred in 250mL of methanol with sufficient p-toluenesulfonic acid monohydrate to make the solution acidic (pH = 1-2). After stirnng overnight, the solution was concentrated under reduced pressure, made basic (pH = 8) with IN sodium hydroxide and extracted into 8X50mL of ethyl acetate. The aqueous layer was saturated with NaCl to aid in extraction of the product The combined extracts were dned over magnesium sulfate and concentrated under reduced pressure Chromatography using a gradient of ethyl acetate then 10% methanol in ethyl acetate followed by tnturation with ether-hexane gave 4.8g of 3-[2-(3-hydroxy-propyl)- benzιmιdazol-l-yl]-propιonιtπle as a solid. Step 3: 3-[2-(3-Oxo-propyl)-benimidazol-l-yI]-propionitrile: To a stirred solution of 0.5g of oxalyl chloπde in 15mL of methylene chloπde cooled to -78°C was added lmL of anhydrous DMSO After 15 min, a solution of lg of 3-[2-(3-hydroxy-propyl)-benzιmιdazol-l-yl]-propιonιtnle in 50mL of methylene chlonde and lOmL of anhydrous DMSO was added while keeping the temperature below - 50°C. There was considerable precipitate which redissolved on warming to 0°C over 20 min. After cooling back down to -50°C, 5mL of tπethyl amine was added and the mixture allowed to warm to room temperature After 15mm, the mixture was diluted with 250mL of water, shaken and separated The organic layer was dned over magnesium sulfate and concentrated under reduced pressure. The crude 3-[2-(3-oxo-propyl)-benιmιdazol-l-yl]-propιonιtnle was an amber resin (lg), and contained only traces of the starting alcohol by TLC (90.10 methylene chloπde:methanol). Step 4: 3-{2-[3-(3-Benzyl-8-aza-bicyclo[3.2.1]oct-8-yl)-propyl]-benzimidazoI-l-yl}- propionitrile: A mixture of 0.25g of 4-benzyl-pιpendιne, 0.4g of l-3-[2-(3-oxo- propyl)-benιmιdazol-l-yl]-propιonιtπle, 5mL of 1,2-dιchloroethane and 0.3g of sodium tπacetoxyborohydπde was stirred at room temperature for 24h. The reaction mixture was diluted with 50mL chloroform and lOmL saturated aqueous Na 2 CO 3 and the layers separated. The aqueous layer was extracted with 2X25mL of chloroform and the combined organic layers dned over magnesium sulfate and concentrated under reduced pressure Low pressure chromatography eluting with a gradient of 70.30 ethyl acetate:methanol to 70:30:5 ethyl acetate:methanol:tnethylamιne gave 400mg of 3-{2-[3-(4-benzyl-pιpeπdιn-l-yl)-propyl]-benzoιmidazol-l-yl}- propionitπle as a gum. Step 5: 2-[3-(3-Benzyl-8-aza-bicyclo[3.2.1]oct-8-yl)-propyl]-lH-benzimidazole: A mixture of 0.4g of 3-{2-[3-(4-benzyl-pιpeπdm-l-yl)-propyl]- benzoιmιdazol-1-y] }-propιonιtnle, 20mL of isopropanol and 2mL of 0.4 M sodium in isopropanol was heated to reflux for 2h. Conversion was complete by TLC (80:20:1 ethyl acetate:methanol:tπethylamme). The mixture was cooled, diluted with lOmL of saturated sodium bicarbonate and concentrated. The residue was partitioned between 3X100mL of chloroform and 50mL of water. After drying over magnesium sulfate and concentration under reduced pressure, the residue was punfied by preparative TLC eluting with 400: 100:25 ethyl acetate:methanol:tπethylamιne. The major band (UV visualization) was 2-[3-(4-benzyl-pιpeπdιn-l-yl)-propyl]-lH-benzιmιdazole (220 mg): MS (m+1) = 334.2; l H NMR (400MHz, CDC1 3 ) 7 4 (d, 2H), 7.32 (m, 2H), 7.25 (m,lH), 7.2 (m, 4H), 3.1 (m, 4H), 2.65 (m, 2H), 2.6 (m, 2H), 2.1 (m, 2H), 2.0 (m, 2H), 1.8 (m, 2H), 1.7 (m, IH), 1.5 (m, 2H). EXAMPLE 5 2-[3-(4-Benzyl-piperidin-l-yl)-propyI]-imidazo[4,5-b]pyridine Example 5 was prepared by the following procedure. Step 1: 4-Bromo-butyric acid benzyl ester: To an ice cold solution of 5g of 4-bromobutync acid and 5.5g of benzylchloroformate in lOOmL of dichloromethane was added 5mL of tπethylamme and then 700mg of 4-dιmethylamιnopyndιne. A vigorous exothermic reaction ensued with evolution of carbon dioxide After stirnng for 3h, the mixture was diluted with lOOmL of dichloromethane and washed with 200mL of saturated sodium bicarbonate, dned over magnesium sulfate, and concentrated to an oil. Azeotropic drying with toluene gave 8g of 4-bromobutyπc acid benzyl ester as a clear oil. Step 2: 4-(4-Benzyl-piperidin-l-yl)-butyric acid: A mixture of 0.9g of 4-bromobutyπc acid benzyl ester, 0.5g of 4- benzylpipeπdine, 0.6mL of N,N-dnsopropylethylamιne and 20mL of acetonitπle was heated to 80°C for 4h The mixture was cooled, concentrated under reduced pressure and partitioned between chloroform and saturated sodium carbonate After drying over magnesium sulfate the extracts were concentrated to a thick oil, 1.4g, which was a mixture of the benzyl ester of 4-(4-benzyl-pιpeπdιn-l-yl)-butyπc acid, benzyl 4- bromobutyrate and butyrolactone. Hydrogenation over 0.5g of palladium on carbon in lOOmL of ethanol under latm of hydrogen overnight gave 0.9g of 4-(4-benzyl- pιpeπdιn-l-yl)-butyπc acid after drying under vacuum at 100°C overnight which was homogeneous by TLC (90: 10: 1 chloroform, methanol: ammonium hydroxide). Step 4: 2-[3-(3-Benzyl-8-aza-bicyclo[3.2.1]oct-8-yl)-propyl]-3H-imidazo[4,5-b]pyridine: A mixture of 0.6g of 4-(4-benzyl-pιpendιn-l-yl)-butyπc acid, 0.25g of 1,2-dιamιnopyndιne and 6g of polyphosphoπc acid was heated to 185°C for 2h. The mixture was cooled and stirred with lOOmL of 3N sodium hydroxide for lh after becoming homogeneous. The solution was extracted with 5X100mL of chloroform and the combined extracts washed 3X50mL of dilute ammonium hydroxide, heated with lg of decoloπz g carbon for 10 min, cooled, filtered and concentrated. Punfication of the residue by chromatography, eluting with 400: 100.25 ethyl acetate:methanol:tnethylamιne gave 210mg of 2-[3-(4-benzyl-pιpeπdιn-l-yl)-propyl]- ιmιdazo[4,5-b]pyπdιne: MS (m+1) = 335.2; 1H NMR (400MHz, CDC1 3 ) 8.36 (d, IH), 7.8 (d, IH), 7.6 (d, 0.5H), 7.3-7.1 (complex, 5.5H), 6.85 (d, 0.5H). 6.6 (dd, 0 5H), 3.12 (dd, 2H), 3.0 (d, 2H), 2 6 (d, 2H), 2.55 (dd, 2H), 2.0 (m, 4H), 1.7 (d, 2H), 1.6 (m, IH), 1.5 (m, 2H). EXAMPLE 6 2-[3-(4-Benzyl-piperidin-l-yl)-propyl]-5-fluoro-lH-benzimidazole Example 6 was prepared by the following procedure. Step 1: 5-[2-(4-Benzyl-piperidin-l-yl)-ethyl]-2,2-dimethyl-[l,3]dioxane-4,6-dione: Following the procedure descπbed in S.Danishefsky and R.K.Singh, J. American Chemical Society, 97:3239-3241(1975), a mixture of 0.5g of 4- benzylpipeπdine, lOmL of toluene, and 0.5g of 6,6-dιmethyl-5,7-dιoxa- spιro[2.5]octane-4,8-dιone was stirred for 20h, cooled, and the white solid product collected by filtration and dned under vacuum The yield of 5-[2-(4-benzyl-pιpeπdιn- l-yl)-ethyl]-2,2-dιmethyl-[l,3]dιoxane-4,6-dιone was 0.94 g. Step 2: 2-[3-(4-Benzyl-piperidin-l-yl)-propyI]-5-fluoro-lH-benzimidazole: A mixture of 0.08g of 5-[2-(4-benzyl-pιpeπdιn-l-yl)-ethyl]-2,2- dιmethyl-[l,3]dιoxane-4,6-dιone, lOmL of diglyme and 4 drops of cone hydrochloπc acid was heated to reflux for 18h. The mixture was cooled, and partitioned between dilute aqueous ammonium hydroxide and dichloromethane The combined extracts were dned over magnesium sulfate and concentration under reduced pressure. The residue was punfied by preparative TLC elutmg with 70:30 chloroform:methanol. The major band (UV visualization) was 2-[3-(4-benzyl-pιpeπdιn-l-yl)-propyl]-5- fluoro-lH-benzimidazole (80 mg): MS (m+1) = 352.4; ^H NMR (400MHz, CDC1 3 ) 9.2 (br, IH), 7.32 (m, 2H), 7.25 (m, 2H), 7.2 (m, 2H), 7.15 (m, IH), 6.9 (dd, IH), 3.1 (m, 4H), 2.65 (m, 2H), 2.6 (m, 2H), 2.1 (m, 2H), 2.0 (m, 2H), 1.8 (m, 2H), 1.7 (m, IH), 1.5 (m, 2H). EXAMPLE 7 2-{3-[4-(4-Chloro-benzyl)-piperidin-l-yl]-propyl}-lH-benzimidazole Example 7 was prepared by the following procedure. Step 1: 4-(4-Chloro-benzyIidene)-piperidine-l-carboxylic acid tert-butyl ester: To a stirred solution of 2g of 4-oxo-pιpeπdιne-l -carboxylic acid tert- butyl ester and 3.5g of diethyl 4-chlorobenzylphosphonate in lOmL of 1,3-dιmethyl- 2-ιmιdazohdιnone dned over 4A mol sieves was added 0 50g of 60% sodium hydnde oil dispersion. The mixture was allowed to stir overnight, diluted with 200mL of water and extracted with 3X100mL of ether. Combined extracts were dned over magnesium sulfate and concentrated under reduced pressure. Low pressure chromatography over silica gel eluting with a gradient of 5 95 ethyl acetate:hexane to 1:5 ethyl acetate:hexane gave 2g of 4-(4-chloro-benzyhdene)-pιpeπdme-l -carboxylic acid tert-butyl ester as a colorless oil. Step 2: 5-(4-Chloro-benzyl)-2-aza-bicyclo[2.2.2]octane-2-carboxylic acid ethyl ester: A solution of 2g of 4-(4-chloro-benzylιdene)-pιpendιne-l -carboxylic acid tert-butyl ester and 0.5g of 5% platinum on carbon in lOOmL of ethanol was allowed to stir overnight under latm of hydrogen The catalyst was filtered off and the solution concentrated to give 2g of 4-(4-chloro-benzyl)-pιpeπdιne-l -carboxylic acid tert-butyl ester as an oil. Step 3: 4-(4-Chloro-benzyl)-piperidine: A mixture of 2g of 4-(4-chloro-benzyl)-pιpeπ dine- 1 -carboxylic acid tert-butyl ester, dioxane (1.5mL), and 3N hydrochloπc acid (LOmL, 4equιv ) was heated at reflux for 3.5 hours. The cooled mixture was made basic with saturated sodium carbonate solution and extracted with chloroform (3xl0mL). The combined extracts were dned over magnesium sulfate and concentrated under reduced pressure The crude product (1.2g) was an oil Step 4 and 5: 2-{3-[4-(4-Chloro-benzyl)-piperidin-l-yl]-propyl}-lH-benzimidazole: Steps 4 and 5 were performed in a similar manner to Example 4, but substituting 4-(4-chloro-benzyl)-piperidine for 4-benzylpiperidine in Step 4. Purification by chromatography eluting with 90: 10 CHCl3:MeOH gave 2-{3-[4-(4- chloro-benzyl)-piperidin-l-yl]-propyl}-lH-benzimidazole: MS (m+1) = 369; *H NMR (400MHz, CDC1 3 ) 9.75 (br, IH), 7.7 (br, IH), 7.5 (br, IH), 7.4 (d, 2H), 7.32 (d, 2H), 7.2 (d, 2H), 3.1 (m, 4H), 2.65 (m, 2H), 2.6 (m, 2H), 2.1 (m, 2H), 2.0 (m, 2H), 1.75 (d, 2H), 1.7 (m, IH), 1.5 (m, 2H). EXAMPLE 8 2-{3-[4-(4-Methyl-benzyl)-piperidin-l-yl]-propyl}-lH-benzimidazole Example 8 was prepared in a similar manner to Example 6, but substituting 4-(4-methyl-benzyl)-piperidine for 4-(4-chloro-benzyl)-piperidine in Step 4. Purification by chromatography eluting with 90: 10 CHCl3:MeOH gave 2-{3-[4- (4-methyl-benzyl)-piperidin-l-yl]-propyl }-lH-benzimidazole: MS (m+1) = 348.5; ^H NMR (400MHz, CDCI3) 9.75 (br, IH), 7.7 (br, IH), 7.5 (br, IH), 7.4 (m, 2H), 7.3-7.2 dd, 4H), 3.1 (m, 4H), 2.65 (m, 2H), 2.6 (m, 2H), 2.4 (s, 3H), 2.1 (m, 2H), 2.0 (m, 2H), 1.8 (d, 2H), 1.7 (m, IH), 1.5 (m, 2H). EXAMPLE 9 2- [3-(4-Benzyl-piperidin- 1 -yl)- 1-methy 1-propyl] - lH-benzimidazole Example 9 was prepared by the following procedure. Step 1: 3-(lH-Benzimidazol-2-yl)-butan-l-ol: Following the general procedure descπbed in A.R.Fπedman, D.S.Payne and A.R.Day, J. Heterocyclic Chemistry, 3:257-259(1966), a mixture of 9g of 1,2-phenylenedιamιne dihydrochlonde and 7g of 2-methylbutyrolactone in 60mL of 4N hydrochloπc acid was heated to reflux for 4 days, 1 teaspoon of decoloπzmg carbon added, and after another 15mm reflux, filtered hot. The filtrate was concentrated under reduced pressure to near dryness, the residue made basic (pH = 8) with ammonium hydroxide and extracted into 3X100mL of ethyl acetate.. The combined extracts were dned over magnesium sulfate and concentrated under reduced pressure. After drying under vacuum, 12g of 3-(lH-benzιmιdazol-2-yl)-butan-l-ol was obtained as a resin. Step 2: 3-[2-(3-Hydroxy-l-methyl-propyl)-benzimidazol-l-yI]-propionitrile: A mixture of 6g of 3-(lH-benzιmιdazol-2-yl)-butan-l-ol, 20mL of acetic acid and 5mL of acetic anhydnde was heated to reflux for 4h. The mixture was cooled, concentrated, added lOOmL of methanol and again concentrated under reduced pressure. Azeotropically dned under reduced pressure with 200mL of toluene, then under vacuum overnight To a stirred solution of the crude acetate of 3- (lH-benzιmιdazol-2-yl)-butan-l-ol, 8.3g, in 250mL of acetomtπle was added 5mL of acrylonitπle, 2 drops of IM tetrabutylammonium fluonde in THF and dropwise ION NaOH until basic. After heating to 85°C for 16h, the mixture was cooled, concentrated under reduced pressure, and partitioned between 2X300mL of ethyl acetate and lOOmL of water The combined extracts were dned over magnesium sulfate and concentrated under reduced pressure The residue was tπturated with 25mL of ethyl acetate, cooled in an ice bath and filtered The resulting white solid, 3.0g, was 3-[2-(3-hydroxy-l-methyl-propyl)-benzιmιdazol-l-yl]-propιonιtnle. Step 3: 3-[2-(l-Methyl-3-oxo-propyl)-benzoimidazol-l-yl]-propionitrile: To a stirred solution of LOmL of oxalyl chloπde in 20mL of methylene chloπde cooled to -78°C was added 2mL of anhydrous DMSO. After 15mm, a solution of lg of 3-[2-(3-hydroxy-l-methyl-propyl)-benzoιmιdazol-l-yl]-propιonιtnle in 20mL of anhydrous DMSO and 50mL of methylene chlonde was added keeping the temperature below -50°C. After lOmin, lOmL of tnethyl amine was added and the mixture allowed to warm to room temperature. After 15mm, the mixture was diluted with 250mL of water, shaken and separated. The organic layer was dned over magnesium sulfate and concentrated under reduced pressure. The crude 3-[2-(3-oxo- propyl)-benzιmιdazol-l-yl]-propιonιtnle was an amber resin (1.2g), and contained only traces of the starting alcohol by TLC (90:10 methylene chloπde:methanol) Step 4: 3-{2-[3-(4-Benzyl-piperidin-l-yl)-l-methyl-propyl]-benzimidazol-l-yl}- propionitrile: A mixture of 0.3g of 4-benzyl-pιpendιne, 0.2g of 3-[2-(3-oxo-propyl)- benzιmιdazol-l-yl]-propιonιtπle, 5mL of 1,2-dιchloroethane and 0.3g of sodium tπacetoxyborohydπde was stirred at room temperature for 24h. The reaction mixture was diluted with 50mL chloroform and lOmL saturated aqueous Na 2 CO3 and the layers separated. The aqueous layer was extracted with 2X25mL of chloroform and the combined organic layers dned over magnesium sulfate and concentrated under reduced pressure. Low pressure chromatography eluting with a gradient of 70:30 ethyl acetate: methanol to 80:20:2 ethyl acetate:methanol tπethylamine gave 205mg of 3-{2-[3-(4-benzyl-pιpendιn-l-yl)-l-methyl-propyl]-benzιmιdazol-l-yl}-propιonιtπle as a gum. 2-[3-(3-Benzyl-8-aza-bicyclo[3.2.1]oct-8-yl)-propyl]-lH-benzimidazole: A mixture of 0.2g of 3-{2-[3-(4-benzyl-pιpendιn-l-yl)-l-methyl- propyl]-benzιmιdazol-l-yl }-propιonιtπle, lOmL of tert-butanol and lg of potassium tert-butoxide was heated to reflux for 10 min Conversion was complete by TLC (80.20:1 ethyl acetate:methanol:tπethylamιne) The mixture was cooled, diluted with lOmL of saturated sodium bicarbonate and concentrated The residue was partitioned between 3X100mL of chloroform and 50mL of water After drying over magnesium sulfate and concentration under reduced pressure, the residue was puπfied by preparative TLC eluting with 450:50:10 chloroform:methanol:ammonιurn hydroxide The major band (UV visualization) was 2-[3-(4-benzyl-pιpeπdιn-l-yl)-l-methyl- propyl]-lH-benzιmιdazole (82 mg): MS (m+1) = 348.5, 1H NMR (400MHz, CDC1 3 ) 7.42 (s, 2H), 7.3 (m, 2H), 7.25 (m, IH), 7.2 (m, 4H), 3.25 (m, IH), 3.08 (m, 2H), 2.65 (d, 2H), 2.6 (m, IH), 2.5 (m, IH), 2.1 (m, 2H), 1.95 (m, 2H), 1.8 (d, 2H), 1.7 (m, IH), 1.5 (d, 3H), 1.5 (m, IH). EXAMPLE 10 2-[3-(4-Benzyl-piperidin-l-yI)-butyl]-lH-benzimidazole Example 10 was prepared by the following procedure. 4-(lH-Benzimidazol-2-yl)-butan-2-ol: A mixture of 8g of 1,2-phenylenedιamιne and 6.6g of 4-pentenoιc acid in 50mL of 4N hydrochloπc acid was heated to reflux for 18 hours, cooled in an ice bath, made basic (pH = 8) with ammonium hydroxide and extracted into 3X100mL of ethyl acetate. The combined extracts were dned over magnesium sulfate and concentrated under reduced pressure. After drying under vacuum, 10g of 4-(lH- benzιmιdazol-2-yl)-butan-2-ol was obtained as a thick oil which slowly crystallized. Acetic acid 3-[l-(2-cyano-ethyl)-lH-benzoimidazol-2-yl]-l-methyl-propyl ester: A mixture of 6g of 4-(lH-benzιmιdazol-2-yl)-butan-2-ol, 20mL of acetic acid and 5mL of acetic anhydnde was heated to reflux for 6h The mixture was cooled, concentrated, added lOOmL of methanol and again concentrated under reduced pressure. Azeotropic drying under reduced pressure with 200mL of toluene, then under vacuum overnight gave 8.3g of the acetate of 4-(lH-benzιmιdazol-2-yl)- butan-2-ol as a crystalline solid To a stirred solution of 7.5g of the acetate of 4-(lH- benzιmιdazol-2-yl)-butan-2-ol in 250mL of acetomtnle was added 5mL of acrylonitπle, 2 drops of IM tetrabutylammonium fluonde in THF and dropwise ION NaOH until basic. After heating to 85°C for 46h, the mixture was cooled, concentrated under reduced pressure, and partitioned between 2X300mL of ethyl acetate and lOOmL of water. The combined extracts were dned over magnesium sulfate and concentrated under reduced pressure. Punfication of the residue by low pressure chromatography eluting with ethyl acetate gave 9.2g of the acetate ester of 3- [2-(3-hydroxy-butyl)-benzιmιdazol-l-yl]-propιonιtπle as a resin 3-[2-(3-Hydroxy-butyl)-benzimidazol-l-yl]-propionitrile: A mixture of 8.1g of the acetate ester of 3-[2-(3-hydroxy-butyl)- benzιmιdazol-l-yl]-propιonιtπle (Product of Step 2), lOOmL of methanol, 25mL of water and 1.2g of lithium hydroxide monohydrate was stirred for 12h at room temperature, concentrated under reduced pressure diluted with 50mL of water and extracted with 3X100mL portions of ethyl acetate. Combined extracts were dned over magnesium sulfate, concentrated under reduced pressure and dned azeotopically with toluene. Drying under vacuum gave 7.6g of 3-[2-(3-hydroxy-butyl)- benzιmιdazol-l-yl]-propιonιtnle as a thick oil. Step 4: 3-[2-(3-Oxo-butyl)-benzimidazol-l-yl]-propionitrile: To a stirred solution of LOmL of oxalyl chloride in 30mL of methylene chloride cooled to -78°C was added 2mL of anhydrous DMSO. After lOmin, a solution of 2.1 g of 3-[2-(3-hydroxy-butyl)-benzimidazol-l-yl]-propionitrile in 150mL of dichloromethane was added keeping the temperature below -50°C. After lOmin, lOmL of triethyl amine was added and the mixture allowed to warm to room temperature. After 15min, the mixture was diluted with 250mL of water, shaken and separated. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. Drying under vacuum gave 2.2g of 3-[2-(3-oxo-butyl)- benzimidazol-l-yl]-propionitrile as an amber resin. 3-{2-[3-(4-Benzyl-piperidin-l-yl)-butyl]-benzimidazol-l-yI}-propionitrile: A mixture of 0.3g of 4-benzyl-piperidine, 0.24g of 3-[2-(3-oxo-butyl)- benzimidazol-l-yl]-propionitrile, 5mL of 1,2-dichloroethane and 0.3g of sodium triacetoxyborohydride was stirred at room temperature for 3 days. The reaction mixture was diluted with 50mL chloroform and lOmL saturated aqueous Na 2 CO 3 and the layers separated. The aqueous layer was extracted with 2X25mL of chloroform and the combined organic layers dried over magnesium sulfate and concentrated under reduced pressure. Low pressure chromatography eluting with a gradient of 80:20 ethyl acetate:methanol to 80:20:5 ethyl acetate:methanol:triethylamine gave 320mg of 3-{ 2-[3-(4-benzyl-piperidin-l-yl)-butyl]-benzimidazol-l-yl }-propionitrile as a resin. 2-[3-(4-Benzyl-piperidin-l-yl)-butyl]-lH-benzimidazole: A mixture of 0.32g of 3-{2-[3-(4-benzyl-pιpendιn-l-yl)-butyl]- benzιmιdazol-l-yl }-propιonιtπle, lOmL of tert-butanol and lg of potassium tert- butoxide was heated to reflux for 10 mm. Conversion was complete by TLC (80:20: 1 ethyl acetate:methanol:tπethylamme). The mixture was cooled, diluted with lOmL of saturated sodium bicarbonate and concentrated. The residue was partitioned between 3X100mL of chloroform and 50mL of water. After drying over magnesium sulfate and concentration under reduced pressure, the residue was puπfied by preparative TLC eluting with 90: 10:2 chloroform:methanol:ammonιum hydroxide. The major band (UV visualization) was 2-[3-(4-benzyl-pιpeπdιn-l-yl)-butyl]-lH-benzιmιdazole (250 mg): MS (m+1) = 348.5; l H NMR (400MHz, CDC1 ) 7.42 (s, 2H), 7.3 (m, 2H), 7.25 (m, IH), 7.2 (m, 4H), 3.25 (m, IH), 3.0 (m, 2H), 2.8 (d, 2H), 2.65 (m, 2H), 2.5 (m, 2H), 2.1 (m, 2H), 1.6 (d, 2H), 1.3 (m, IH), 1.2 (d, 3H), 1.0 (m, IH). EXAMPLE 11 2-[3-(4-Benzyl-3-methyl-piperidin-l-yl)-propyl]-lH-benzimidazole Example 11 was prepared by the following procedure. Step 1: l-Benzyl-4-benzylidene-3-methyl-piperidine: To a stirred solution of 2.1g of l-benzyl-3-methyl-pιpendιn-4-one and 2 5g of diethyl benzylphosphonate in 5mL of l,3-dιmethyl-2-ιmιdazohdιnone dned over 4A mol sieves was added 0.50g of 60% sodium hydnde oil dispersion. The mixture was allowed to stir 2 days, diluted with 400mL of water and extracted with 3X50mL of ether Combined extracts were dned over magnesium sulfate and concentrated under reduced pressure. Low pressure chromatography over silica gel elutmg with a gradient of 5-95 ethyl acetate: hexane to L4 ethyl acetate: hexane gave 2.7g of l-benzyl-4-benzyhdene-3-methyl-pιpendιne as a colorless oil. Step 2: 4-Benzyl-3-methyl-piperidine: A solution of 2.7g of l-benzyl-4-benzyhdene-3-methyl-pιpeπdιne and 2g of 20% palladium hydroxide on carbon m 125mL of ethanol was shaken 3 days under 55psι of hydrogen The catalyst was filtered off and the solution concentrated to give 2g of a mixture of cis and trøn.s-4-benzyl-3-methyl-pιpendιne as an oil Step 4 and 5: 2-[3-(4-Benzyl-3-methyl-piperidin-l-yl)-propyl]-lH-benzimidazole: Steps 4 and 5 were performed a similar manner to Example 5, but substituting 4-benzyl-3-methyl-pιpendιne for 4-benzylpιpeπdιne in Step 4 Punfication by chromatography elutmg with 225:20:5 chloroform:methanol:ammonιum hydroxide gave cis and trans 2-[3-(4-benzyl-3- methyl-pιpendιn-l-yl)-propyl]-lH-benzιmιdazole as close moving bands: MS (m+1) = 348.5; IH NMR (400MHz, CDCI 3 ) 7.58 (d, 2H), 7.2- 7.0 (m, 7H), 3.0 (m, 4H), 2.5 (m, 4H), 2.0 (m, 2H), 1.6 (m, 2H), 1.1 (2 x d, 3H), 1.0 (m, 2H). EXAMPLE 12 N-[2-(4-Benzyl-piperidin-l-ylmethyl)-3H-benzoimidazol-5-yl]- methanesulfonamide. Example 12 was prepared by the following general procedure. To a solution of 4-benzylpiperidine (l.Og, 5.7mmol) in DMF (20mL) was added ethylbromoacetate (637μL, 5.7mmol) and the reaction mixture was stirred at room temperature for 4h The reaction mixture was partitioned between EtOAc and aqueous NaHCO,, the organic layer was dned over Na,S0 4 , filtered and concentrated The crude oil was punfied by silica gel chromatography (gradient elution, 4: 1 hexanes:EtOAc to EtOAc) to give the ethyl ester The ethyl ester (700mg, 2.6mmol) was dissolved in 6N HCl (5mL) and heated to reflux for lh. The reaction mixture was cooled and concentrated to give (Intermed. 15) Intermed. 15 as a white solid. To a solution of carboxylic acid Intermed. 15 (117 mg, 0.5mmol) in DMF (3mL) was added EDC (96mg, 0.5mmol), HOBt (68mg, 0.5mmol), and N-(3,4- dιammo-phenyl)-methanesulfonamιde (lOOmg, 0.5mmol). The reaction mixture was stirred at room temperature for lh followed by quenching with aqueous ΝaHCO, and EtOAc. The layers were separated and the organic was washed twice with water, dned over Νa_,SO 4 , filtered and concentrated. The crude oil was dissolved in AcOH and heated to reflux for 15mm. The reaction mixture was cooled, concentrated and punfied by reverse-phase HPLC to give N-[2-(4-Benzyl-pιpendιn-l-ylmethyl)-3H- benzoιmιdazol-5-yl]-methanesulfonamιde (90 mg): Η ΝMR (300MΗz, CDOD) δ 7.82 (d, 1 H), 7.77 (s, 1 H), 7.49 (d, 1 H), 7.32-7.17 (m, 5 H), 4.92 (s, 2 H), 3.70 (d, 2 H), 3.02 (s, 2 H), 2.60 (d, 2 H), 2 00-1.88 (m, 3 H), 1 70 (m, 2 H); mass spectrum m/z 399 [(M+H) + ; calcd for C 21 H, 7 Ν 4 O 2 S: 399].

Claims: WHAT IS CLAIMED IS 1. A compound having the formula: (I) or a pharmaceutically acceptable salt thereof, wherein Rj is 1) 2-benzιmιdazole, 2-ιmιdazopyndιne, 2-mdole, punne, or 2- quinazohne, each optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cj-C4alkyl, tπfluoromethyl, C\- C4alkylsulfonamιde, hydroxy, or carboxy; or n) phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cι-C4alkyl, tπfluoromethyl, Ci-C4alkylsulfonamιde, hydroxy, or carboxy; R2 is a) 2-benzιmιdazole, 2-ιmιdazopyndme, 2-ιndole, puπne, or 2- quinazoline, each optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cι-C4alkyl, tnfluoromethyl, Ci- C4alkylsulfonamιde, hydroxy, or carboxy; or b) phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cj-C4alkyl, tπfluoromethyl, Cι -C4alkylsulfonamιde, hydroxy, or carboxy, When Rj is l, then R2 is b; when Ri is n, then R2 is a; When R or R2 is 2-benzιmιdazole, respective Lj or L2 is not Ci- C2alkyl, except when Ri or R2 is hydroxy-substituted 2-benzιmιdazole, respective Lj or L2 includes Cj-C2alkyl Lj and L2 are independently Cj-C4alkyl, Cι-C4alkenyl, C\- C4alkynyl, Cι-C4alkoxy, amιnoCι-C4alkyl, hydroxyCi-C4alkyl, carbonyl, cycloC3- C6alkyl or aminocarbonyl; and optionally substituted at any of the 2, 3, 5, or 6 positions independently with X, wherein X is hydroxy, amino, Cj-C4alkylamιno, dι(Ci-C4)alkylamιno, Ci- C4alkyl, ester, carbamate, carbonate, or ether. 2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein Rj IS 2-ιmιdazopyπdιne, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cj-C4alkyl, tnfluoromethyl, Ci-C4alkylsulfonamιde, hydroxy, or carboxy; R2 is phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Ci-C4alkyl, tπfluoromethyl, Cι -C4alkylsulfonamιde, hydroxy, or carboxy; Lj and L2 are independently Cj-C4alkyl, Ci-C4alkenyl, Cj- C4alkynyl, Cι-C4alkoxy, amιnoCι -C4alkyl, hydroxyC -C4alkyl, carbonyl, cycloC3- Cόalkyl or aminocarbonyl; and optionally substituted at any of the 2, 3, 5, or 6 positions independently with X, wherein X is hydroxy, amino, C -C4alkylamιno, dι(Cι-C4)alkylamιno, C - C4alkyl, ester, carbamate, carbonate, or ether. 3. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein Rj is punne, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cι -C4alkyl, tπfluoromethyl, Ci-C4alkylsulfonamιde, hydroxy, or carboxy; R2 is phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cι -C4alkyl, tnfluoromethyl, Cι-C4alkylsulfonamιde, hydroxy, or carboxy, Li and L2 are independently Cι -C4alkyl, Cj-C4alkenyl, Ci- C4alkynyl, Ci-C4alkoxy, amιnoCι-C4alkyl, hydroxyC -C4alkyl, carbonyl, cycloC3- Cόalkyl or aminocarbonyl; and optionally substituted at any of the 2, 3, 5, or 6 positions independently with X, wherein X is hydroxy, amino, Cι-C4alkylammo, dι(Cι-C4)alkylamιno, Ci- C4alkyl, ester, carbamate, carbonate, or ether. 4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein Rj IS 2-benzιmιdazole, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, C]-C4alkyl, tnfluoromethyl, Ci-C4alkylsulfonamιde, hydroxy, or carboxy; R2 is phenyl, optionally substituted with one to five substituents, each substituent independently being chloro, fluoro, bromo, Cj-C4alkyl, tnfluoromethyl, Cι-C4alkylsulfonamιde, hydroxy, or carboxy; Li is not Cj-C2alkyl, except when Rj is hydroxy-substituted 2- benzimidazole, Lj includes Cj-C2alkyl; L] and L2 are independently Ci -C4alkyl, C -C4alkenyl, Ci- C4alkynyl, Ci-C4alkoxy. amιnoCι-C4alkyl, hydroxyCι-C4alkyl, carbonyl, cycloC3- Cόalkyl or aminocarbonyl; and optionally substituted at any of the 2, 3, 5, or 6 positions independently with X, wherein X is hydroxy, amino, Ci-C4alkylammo, dι(Cι-C4)alkylammo, Ci- C4alkyl, ester, carbamate, carbonate, or ether 5. The compound according to claim 1, wherein said compound is 2-(4-Benzyl-pιpendm-l-ylmethyl)-ιmιdazo[4,5-b]pyπdιne, 8-(4-Benzyl-pιpendιn-l-ylmethyl)-punne; 2-(4-Benzyl-pιpeπdιn-l-ylmethyl)-ιmιdazo[4,5-c]pyπdιne; 2-[3-(4-Benzyl-pιpendιn-l-yl)-propyl]-lH-benzιmιdazole; 2-[3-(4-Benzyl-pιpendm-l-yl)-propyl]-ιmιdazo[4,5-b]pyπdιne; 2-[3-(4-Benzyl-pιpeπdιn-l-yl)-propyl]-5-fluoro-lH-benzιmιdazole, 2-{3-[4-(4-Chloro-benzyl)-pιpeπdιn-l-yl]-propyl }-lH-benzιmιdazole; 2-{ 3-[4-(4-Methyl-benzyl)-pιpendm-l-yl]-propyl}-lH-benzιmιdazole; 2-[3-(4-Benzyl-pιpeπdm-l-yl)-l-methyl-propyl]-lH-benzιmιdazole; 2-[3-(4-Benzyl-pιpendιn-l-yl)-butyl]-lH-benzιmιdazole, 2-[3-(4-Benzyl-3-methyl-pιpeπdm-l-yl)-propyl]-lH-benzιmιdazole; or N-[2-(4-Benzyl-pιpeπdιn-l-ylmethyl)-3H-benzoιmιdazol-5-yl]-methanesulfonamιde. 6. The compound according to claim 1, wherein said compound is or 7. A pharmaceutical composition compπsing an inert earner and an effective amount of a compound according to claim 1. 8. The pharmaceutical composition according to claim 7 useful for the treatment of pain. 9. The pharmaceutical composition according to claim 7 useful for the treatment of migraine, depression, anxiety, schizophrenia, Parkinson's disease, or stroke. 10. A method of treating pain compnsing a step of administeπng to one in need of such treatment an effective amount of a compound according to claim 1. 11 A method of treating migraine, depression, anxiety, schizophrenia, Parkinson's disease, or stroke compnsing a step of administeπng to one in need of such treatment an effective amount of a compound according to claim 1

Inventors: CLAREMON DAVID A, HUSCROFT IAN, KULAGOWSKI JANUSZ, MUNSON PETER M, THOMPSON WAYNE, WHITTER WILLIE, CLAREMON, DAVID, A., HUSCROFT, IAN, KULAGOWSKI, JANUSZ, MUNSON, PETER, M., THOMPSON, WAYNE, WHITTER, WILLIE
Applicants: CLAREMON DAVID A, HUSCROFT IAN, KULAGOWSKI JANUSZ, MERCK & CO INC, MERCK SHARP & DOHME, MUNSON PETER M, THOMPSON WAYNE, WHITTER WILLIE, CLAREMON, DAVID, A., HUSCROFT, IAN, KULAGOWSKI, JANUSZ, MERCK & CO., INC., MERCK SHARP & DOHME LIMITED, MUNSON, PETER, M., THOMPSON, WAYNE, WHITTER, WILLIE
Application year: 2000
Main classification: C07D
IPC codes: A61K31, A61P9, A61P25, A61P43, C07D401, C07D471, C07D473, C07D487