FORM 2 The Patents Act, 1970 (39 of 1970) & The Patent Rules, 2003 COMPLETE SPECIFICATION (See section 10 and rule 13) "NOVEL AMIDES USEFUL FOR TREATING PAIN." Abbott Laboratories, a company incorporated in USA having its Registered Office at Dept. 377 Bldg. AP6A-1, 100 Abbott Park Road, Abbott Park, IL 60064-6008, USA. The following specification particularly describes the invention and the manner in which it is to be performed WO 2005/007642 PCTYUS2004/021836 NOVEL AMIDES USEFUL FOR TREATING PAIN 5 TECHNICAL FIELD The present invention relates to compounds of formula (I-VII) that are useful for treating pain, pharmaceutical compositions containing compounds of formula (I-VII) that are useful in treating pain, and methods of treating pain using compounds of formula (T-VTTY 10 BACKGROUND OF INVENTION Pain continues to produce severe distress in people's lives, dominating and disrupting their quality of life. Much of the currently available clinical treatment is only partially effective and may be accompanied by distressing side effects or have abuse potential. The unmet clinical need, the personal suffering, and societal economic costs of pain are 15 substantial. The lack of success in clinical pain therapy exemplifies the need for the discovery of new analgesics. The present invention relates to novel compounds useful as analgesics. SUMMARY OF THE PRESENT INVENTION 20 The present invention discloses novel amides, a method for controlling pain in mammals, and pharmaceutical compositions including those amides. More particularly, the present invention is directed to compounds of general formula (I) R8 (I), 25 or a pharmaceutically acceptable salt or prodrug thereof, wherein A is WO 2005/007642 PCT/US2004/02J836 X2isNorCR2; X3 is 0 or S; R is absent or 0; R1 is hydrogen, lower alkoxy, lower alkenyl, lower alkyl, lower alkylthio, lower 5 alkynyl, lower haloalkoxy, lower haloalkyl, lower haloalkylthio, halogen, hydroxy, mercapto, nitro, RARBNS(0)2- or RARBN-; R2, R3, and R4 are independently hydrogen or halogen; R7 is hydrogen, alkenyl, alkoxy, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkoxycarbonylalkyl, alkylsulfonyl, alkylthio, alkynyl, aryl, arylalkyl, aryloxy, .arylthio, 10 cyanoalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, cycloalkylthio, haloalkoxy, haloalkyl, haloalkylsulfonyl, haloalkylthio, halogen, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, -RCRDN-, (RARBN)carbonyl-, (RARBN)sulfonyI-; orRAS(0)2; R6 and R8 are independently hydrogen, lower alkenyl, lower alkoxy, lower alkyl, 15 lower alkylthio, lower alkynyl, lower haloalkoxy, lower haloalkyl, lower haloalkylthio, halogen, hydroxy, mercapto, orRARBN-;; alternatively, R7 and R$ taken together with the atoms they are attached can form a ring selected from the group consisting of 2,2,3,3-tetrafluoro-2,3-dihydro-ben2o[l,4]dioxinyl; 2,3-tetrahydro-berrzo[l,4]dioxinyI; 2,2-difluoro-benzo[l,3]dioxolyl; and 2,2-dihydro- 20 benzo[l,3]dioxolyl; RA and RB are independently alkyl, hydrogen, haloalkyl, or heterocycle; Re and RD are independently hydrogen, alkenyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkynyl, or (RARBN)carbonyl; L is -Kj> -KJK +Q)* Rft-14 , Rll-14 s ^11-14 -f-N I N-|- -f-N [N-f- 25 Rn-14 » or Rii-i4 > — is absent or a single bond; and Rn, R12, R13, and R]4 are independently hydrogen, alkoxy, alkyl, or hydroxy. 2 WO 2005/007642 PCT/US2004/021836 Also, the present invention is directed to compounds of general formula (III) 5 (III) — is a single bond; X1isCR1; X2 is CR2; Ri is hydrogen, lower haloalkyl or halogen; R2, R3, R4, and R$, are hydrogen; R5 is alkyl, hydrogen, halogen, alkoxy, or haloalkoxy; R7 is alkoxy, alkyl, alkylthio, cycloalkyl, haloalkoxy, haloalkyl, haloalkylsulfonyl, haloalkylthio, halogen, RcRDN-; or RAS(0)2-; R11, R12s Rn, and R14 are hydrogen; and RA, RC and RD are independently hydrogen or alkyl. Also, the present invention is directed to compounds of general formula (VI) 15 \^ wherein X1isNorCR1; X5isNorCR5; 20 X6 is a bond or CR6; X7isNorCR7; X8isNorCR8; X9isNorCR9; 3 WO 2005/007642 PCT/US2004/0218J6 Ri, R5, and R9 are independently selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, haloalkyi and heterocycle; R7 is hydrogen, alkenyl, alkoxy, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkoxycarbonylalkyl, alkylsulfonyl, alkylthio, alkynyl, aryl, arylalkyl, aryloxy, arylthio, 5 cyanoalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, cycloalkylthio, haloalkoxy, haloalkyi, haloalkylsulfonyl, haloalkylthio, halogen, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, RCRDN-, (RARBN)carbonyl-, (RARBN)sulfonyl-; orRAS(0)2-; Rs and R$ are independently hydrogen, lower alkenyl, lower alkoxy, lower alkyl, lower 10 alkylthio, lower alkynyl, lower haloalkoxy, lower haloalkyi, lower haloalkylthio, halogen, hydroxy, mercapto, or RARBN-; RA and RB are independently alkyl, hydrogen, haloalkyi, or heterocycle; and Re and Rp are independently hydrogen, alkenyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkynyl, or (NRARB)carbonyl. 15 DETAILED DESCRIPTION OF THE PRESENT INVENTION (1) Embodiments In the principal embodiment, compounds of formula (I) are disclosed Re O A-lAl I 20 (I), or a pharmaceutically acceptable salt or prodrug thereof, wherein A is X2-X *1 M; NM- #VI- 2Y\I >=N \^p i sn R4 R , R3' , or R3 X1isNorCR1; 25 X2isNorCR2; X3isOorN; R is absent or O; 4 WO 2005/007642 PCT/US2004/021836 Ri is hydrogen, lower alkoxy, lower alkenyl, lower alkyl, lower alkylthio, lower alkynyl, lower haloalkoxy, lower haloalkyl, lower haloalkylthio, halogen, hydroxy, mercapto, nitro, or RARBNS(0)2- or RARBN-; R2> &3> ^d ^4 are independently hydrogen or halogen; 5 R7 is hydrogen, alkenyl, alkoxy, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkxycarbonylalkyl, alkylsulfonyl, alkylthio, alkynyl, aryl, arylalkyl, aryloxy, arylthio, cyanoalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, cycloalkylthio, haloalkoxy, haloalkyl, haloalkylsulfonyl, haloalkylthio, halogen, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, -RCRDN-, 10 (RARBN)carbonyl-, (RARBN)sulfonyl-; or RAS(0)2. R$ and R$ are independently hydrogen, lower alkenyl, lower alkoxy, lower alkyl, lower alkylthio, lower alkynyl, lower haloalkoxy, lower haloalkyl, lower haloalkylthio, halogen, hydroxy, mercapto, or RARBN-; alternatively, R7 and R6 taken together with the atoms they are attached can form a 15 ring selected from the group consisting of 2,2,3,3-tetrafluoro-2,3-dihydro-benzo[l,4]dioxinyl; 2,3-tetrahydro-benzo[l,4]dioxinyl; 2,2-difluoro-benzo[l,3]dioxolyl; and 2,2-dihydro-benzo[l,3]dioxolyI; RA and RB are independently alkyl, hydrogen, haloalkyl, or heterocycle; Re and RD are independently hydrogen, alkenyl, alkoxycarbonyl, alkyl, alkylcarbonyl, 20 alkynyl, or (RARBN)carbonyl; L is -Kj}+ *0)*- -KjD1* Rl1-14 , R11-14 » ^11-14 , s \Z\J s £ \_|V s R11-14 ) or R11-14 ; — is absent or a single bond; and R11' R12, R13, and R14 are independently hydrogen, alkoxy, alkyl, or hydroxy. 25 Another embodiment of the present invention relates to compounds of formula (II) 5 WO 2005/007642 PCT/US2004/021836 & 11 .N R< R11-14 R4 =N ^—^ O R6 R4 (4) R R, R (5> R3 (6) /=Hfi~ *--£>* ^ R'-£KM R4 R^ R=CI, Br, 1 (9) (1) R/ R3—(7 X)^N I NH deprotect^ y-,/ \_L/ (10) + xX —-ML. KIH (10) 0^C'"" (11) "° R<> (12) R1 /R8 R1 /==< (5) R 3 - >=N ^-^ O Rfi 3 (13) Re (14) Amides of general formula (12), wherein Xi, X2, X3, R3, R4, R*> R7, and R$ are as defined in formula (I-IV), can be prepared as described in Scheme 2. tert-Butyl 3,8- 10 diazabicyclo[3.2. l]octane-8-carboxylate, prepared as described in Examples 23A-23I herein, can be treated with 2-halo compounds of general formula (1) as described in Scheme 1 to provide compounds of general formula (9). Compounds of general formula (9) can be deprotected with trifluoroacetic acid in methylene chloride (1:1) or with 4.5N hydrochloric acid in 1,4-dioxane to provide compounds of general formula (10). Compounds of general 22 WO 2005/007042 PCT/US2004/021836 formula (10) can be treated with isocyanates of general formula (11) to provide amides of general formula (12), which are representative of compounds of the present invention. Amides of general formula (13) and amides of general formula (14), wherein X3) R|, R.2, R3, Re, R7, and R8 are as defined in formula (I-IV), can be prepared as described in Scheme 2. Oxazoles or thiazoles of general formula (5) or general formula (7) can be processed in a similar manner as compounds of general formula (1) in Scheme 2 to provide amides of general formula (13) or amides of general formula (14) which are both representative of compounds of the present invention. HN f N 10 / base 3-a . „<]>^ ^ -r^HH )=N X<:L/ O R6 R8 RVX3 _ /-N ^^ O R6 D3 (19) I />-ci R3^N (7) R 23 WO 2005/007642 PCT/US2004/021836 Amides of general formula (17), wherein Xj, X2, X3, R3, R4, R$, R7, and R8 are as defined in formula (I-IV), can be prepared as described in Scheme 3. 8-Benzyl-3,8-diazabicyclo[3.2.1]octane, prepared as described in Examples 23A-23F herein, can be processed as described in Examples 34A-34C to provide tert-butyl 3,8- 5 diazabicyclo[3.2.1]octane-3-carboxylate. tert-Butyl3,8-diazabicyclo[3.2.1]octane-3-carboxylate can be treated with 2-haIo compounds of general formula (1) as described in Scheme 1 to provide compounds of general formula (15). Compounds of general formula (15) can be deprotected with trifluoroacetic acid in methylene chloride (1:1) or with 4.5N hydrochloric acid in 1,4-dioxane to provide compounds of general formula (16). Compounds 10 of general formula (16) can be treated with isocyanates of general formula (11) to provide amides of general formula (17) which are representative of compounds of the present invention. Amides of general formula (18) and amides of general formula (19), wherein X3, Ri, R2, R3, R& R7, and R8 are as defined in formula (I-IV), can be prepared as described in 15 Scheme 3. Oxazoles or thiazoles of general formula (5) or general formula (7) can be processed in a similar manner as compounds of general formula (1) in Scheme 3 to provide amides of general formula (18) or amides of general formula (19) which are representative of compounds of the present invention. Scheme 4 24 WO 2005/007642 PCT/US2004/021836 HN O (20) 0 + C02CH3 (26) (27) Amines of formula (20) when treated with chloropyridines of formula (21), wherein Ri is lower haloalkyl or halogen, in the presence of potassium carbonate in DMSO will provide compounds of formula (22). Compounds of formula (22) when treated with hydrochloric acid will provide compounds of formula (23). Compounds of formula (23.) when treated with lithium diisopropylamine and N-phenyltrifluoromethanesulfonimide will provide compounds of formula (24). Compounds of formula (24) when treated with PdChOPPh^, carbon dioxide, triethylamine in methanol will provide compounds of formula (25). Compounds of formula (25) when treated with sodium hydroxide or lithium hydroxide in alcoholic solvents will provide compounds of formula (26). Compounds of formula (26) when treated with anilines of formula (3) and EDCI will provide compounds of formula (27). Alternatively, compounds of formula (26) when treated with oxalyl chloride followed by treatment with an aniline of formula (3) wherein R«, R7, and R$ are defined in formula I-IV and a base such as triethylamine will provide compounds of formula (27). The preparation of compounds of formula (27) wherein Ri is lower haloalkyl or halogen, particularly trifluoromethane or chloride are representative of compounds of the present invention. Scheme 5 25 WO 2005/007642 a C02Na M 7.34 (m, 2H), 6.86 (dd, 1H), 4.22 (ddd, 1H), 4.05 (m, 1H), 3.96 (m, 1H), 3.02 (m, 1H), 2.94 (m, 1H), 2.42 (m, 1H), 2.14 (m, 1H), 1.96 (m, 1H), 1.30 (s, 9H); MS (ESI, M+H)+ 388. 5 Example 39 l-(3-chloro-2-pyridinvl)4-hydroxy-N-r4-(trifluoromethyl)phenyll-4-piperidinecarboxamide Example 39A 10 methyl 1 -benzyI-4-hydroxy-4-piperidinecarboxylate l-Benzyl-4-hydroxy-4-piperidiDecarbonitrile (30.0 g, 118 mmol) in methanol (590 mL) and concentrated HC1 (590 mL) was heated at reflux for 18 hours. The product was obtained following chromatography (Si02, ethyl acetate:hexane, 1:4). MS (EI, M+H)+ 250. 15 Example 39B methyl 4-hydroxy-4-piperidinecarboxylate Methyl l~benzyM-hydroxy-4-piperidinecarboxylate in methanol was treated with Pd(OH)2 (20% on carbon, 500 mg) under a hydrogen atmosphere. The mixture was allowed to stir at room temperature for 12 hours, filtered, and the filtrate was concentrated under 20 reduced pressure. Example 39C methyl 1 -(3-chloro-2-pyridinyl)-4-hydroxy-4-piperidinecarboxylate Methyl l-benzyl-4-hydroxy-4-piperidinecarboxylate (15.0 g, 77 mmol), 2,3- 25 dichloropyridine (12.0 g, 81 mmol), and potassium carbonate (15.0 g, 108.7 mmol) were combined in DMF (200 mL) and heated at 90 °C for 2 days. The mixture was allowed to cool to room temperature, concentrated, and standard work-up provided a residue that was purified via chromatography (S1O2, ethyl acetate:hexanes, 1:6) to provide the title compound MS(EI,M+H)+271. 30 Example 39D 1 -(3-chloro-2-pyridinyl)-4-hydroxy-4-piperidinecarboxylic acid 44 WO 2005/007642 PCT/US2004/021836 The title compound was prepared using the procedure described in Example 37D substituting methyl l-(3-chloro-2-pyridinyI)-4-hydroxy-4-piperidinecarboxylate for ethyl 1-(3-chloro-2-pyridinyl)-3-hydroxy-4-piperidinecarboxylate. 5 Example 39E l-(3-chloro-2-pyridinvn-4-hvdroxy-N-r4-(trifluoromethyl)phenyl1-4--piperidinecarboxamide l-(3-Chloro-2-pyridinyl)-4-hydroxy-4-piperidinecarboxylic acid, EDCI (525 mg, 2.7 mmol), and 4-(trifluoromethyl)aniline in dichloromethane (10 mL) were combined at room . temperature and stirred overnight. Standard work-up gave a crude product which was 10 purified via chromatography (Si02, ethyl acetate:hexanes, 1:9). !H NMR (500 MHz, CDC13) δ 8.90 (s(br), 1H), 8.20 (dd, 1H), 7.74 (d, 2H), 7.61 (m, 3H), 6.86 (dd, 1H), 3.80 (m, 2H), 3.18 (m, 2H), 2.50 (m, 2H), 1.78 (m, 2H); MS (ESI, M+H)+ 400. Example 40 15 N-(44ert-butylphenyl)0'-(trifluoromethyl)-3,6-dihydro-2H-l,2t-bipyridine-4-carboxamide Example 40A l-[3-(trifluoromethyl)pyridin-2-yl]piperidin-4-one 2-Chloro-3-(trinuoromethyl)pyridine (11.92 g, 65.7 mmol)), K2CO3(19.10 g, 138 20 mmol), and l,4-dioxa-S-azaspiro[4.5]decane (8.85 mL, 69.0 mmol) were combined in DMSO (65 mL) and stirred at 100 °C for 3 hours. The mixture was treated with additional 1,4-dioxa-8-azaspiro[4.5]decane (2.0 mL, 16 mmol), stirred for 2 hours, treated with additional 1,4-dioxa-8-azaspiro[4.5]decane (1.0 mL, 7.8 mmol), and stirred for 1 hour. The mixture was diluted with diethyl ether (200 mL), washed with water (250 mL), washed with brine (100 25 mL), dried (Na2S04), filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in concentrated HC1 (25 mL), stirred for 3 hours, basified with concentrated NH4OH, extracted with CH2CI2, and the phases separated. The organic phase was dried (Na2S04), filtered, and the filtrate concentrated under reduced pressure. The residue was purified via flash chromatography (20% to 40 % diethyl ether/hexanes) to 30 provide the title compound. Example 40B 45 WO 2005/007642 PCT/US2004/021836 methyl 3'-(trifluoromethyl)-3,6-dihvdro-2H-L2'-bir)vridine-4-carboxylate Lithium diisopropyl amide (37.3 mmol) in THF (75 mL) at-78 °C was treated with 1-[3-(trifluoromethyl)pyridin-2-yI]piperidin-4-one (8.30 g, 34.0 mmol) in THF (25 mL) and stirred for 45 minutes. The mixture was treated with solid PhNTf2 (14.0 g, 39.1 mmol), 5 stirred for 1 hour, and concentrated under reduced pressure. The residue was diluted with ethyl aeetate:hexanes (1:1), washed with IN NaOH, dried (Na2S04), filtered through a silica plug, and the filtrate was concentrated under reduced pressure. The residue, triethylamine (14.2 mL, 102 mmol), and PdCl2(PPh3)2 (0.944 g, 1.34 mmol) were combined in methanol (7.00 mL, 173 mmol) and DMF (100 mL) and saturated with carbon monoxide gas (bubbling 10 15 minutes). The mixture was heated at 80 °C under a carbon monoxide atmosphere (1 atn) overnight. The mixture was concentrated to half volume, diluted with diethyl ether, washed with water, brine, dried (Na2S04), filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (6% ethyl acetate/hexanes) to provide the title compound. 15 Example 40C 3'-(trifluoromethyl)-3,6-dihvdro-2H-l,2'-bipyridine-4-carboxyh'cacid Methyl 3’-(trifluoromethyl)-3,6-dihydro-2H-1,2’-bipyridine-4-carboxylate (15 mL) in THF (30 mL) was treated with IN NaOH (27 mL) and stirred for 2 hours. The mixture was 20 treated with additional IN NaOH (16 mL), stirred for 1 hour, treated with IN NaOH (14.5 mL), and stirred for 1 hour. The mixture was diluted with water and extracted with CH2CI2. The aqueous layer was then acidified with concentrated HC1 and extracted with CHCI3. The organic layer was dried (Na2S04), filtered, and the filtrate was concentrated under reduced pressure to provide the title compound. 25 Example 40D N-(4-tert-butylphenyl)-3'-(trifluoromethyl)-3,6-dihydro-2H-1,2’-bipyridine-4-carboxamide 3’-(Trifluromethyl)-3,6-dihydro-2H-1,2’-bipyridine-4-carboxylic acid (0.300 g, 1.10 mmol) and a catalytic amount of DMF were combined in CH2CI2 (4.0 mL) and treated with 30 (COCl)2 (0.14 mL, 1.6 mmol). The mixture was stirred for 90 minutes, diluted with toluene (0.5 mL) and concentrated to dryness. The residue was dissolved in CH2CI2 (4.0 mL) treated with pyridine (0.14 mL, 1.7 mmol), a catalytic amount of DMAP, and 4-tert-butylaniline 46 WO 2005/007642 PCT/US2004/021836 (0.21 mL, 1.3 mmol). After 1 hour, the mixture was diluted with water and extracted with CH2CI2. The organic phase was dried (Na2S04), filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (2.5% ethyl acetate/CH2Cl2) to provide the title compound. ]H NMR (300 MHz, CDC13) δ 8.42 (dd, IH), 5 7.89 (dd, IH), 7.47 (d, 3H), 6.98 (dd, IH), 6.76 (s, IH), 4.06 (q, 2H), 3.53 (t, 2H), 2.67 (m, 2H);MS(m/z)404. Example 41 N-(4-cMorophenyl)-3'-(trifluoromemyl)-3,6-dihvdro-2H-l,2'-bipyridine-4-carboxamide 10 The title compound was prepared using the procedure described in Example 40D using 4-chloroaiuline instead of 4-tert-butylaniline. lK NMR (300 MHz, CDCI3) δ 8.42 (dd, IH), 7.89 (dd, IH), 7.51 (dd, 2H), 7.43 (brs, IH), 7.30 (d, 2H), 6.99 (dd, IH), 6.77 (sept, IH), 4.05 (q, 2H), 3.51 (t, 2H), 2.65 (m, 2H); MS (m/z) 382. 15 Example 42 N-[4-(trifluoromethoxy)phenyll-3'-(trifluoromethyl)-316-dihydro-2H-l,2'-bipyridine-4- carboxamide The title compound was prepared using the procedure described in Example 40D using 4-(trifluoromethoxy)aniline instead of 4-tert-butylaniline. *H NMR (300 MHz, CDC13) 20 5 8.44 (dd, IH), 7.90 (dd, IH), 7.59 (d, 2H), 7.48 (brs, IH), 7.20 (d, 2H), 7.00 (dd, IH), 6.79 (m, IH), 4.07 (q, 2H), 3.53 (t, 2H), 2.67 (m, 2H); MS (m/z) 432. Example 43 3'-(trifluoromemyl)-N-{44(trifluoromemyl)thio1phenyl-3,6-dihydro-2H-l,2'-bipyridine-4- 25 carboxamide The title compound was prepared using the procedure described in Example 40D using 4-[(trifluoromethyl)thio]aniline instead of 4-tert-butylaniline. 'H NMR (300 MHz, CDCI3) δ 8.43 (dd, IH), 7.90 (dd, IH), 7.66 (d, 2H), 7.62 (d, 2H), 7.53 (brs, IH), 7.00 (dd, IH), 6.79 (m, IH), 4.07 (q, 2H), 3.52 (t, 2H), 2.67 (m, 2H); MS (m/z) 448. 30 Example 44 47 WO 2005/007642 PCT/US2004/021836 3'-(trifluoromethyl)-N-M4(trifluoromethyl)sulfonyl]phenyl}-3,6-dihydro-2H-1,2’-bipyridine- 4-carboxamide The title compound was prepared using the procedure described in Example 40D using 4-[(trifluoromethyl)sulfonyl]aniline instead of 4-tert-butyIaniline. *H NMR (300 MHz, 5 CDC13) δ 8.43 (dd, IH), 8.00 (dd, IH), 7.88-7.92 (m, 3H), 7.75 (brs, IH), 7.02 (dd, IH), 6.85 (m, IH), 4.09 (q, 2H), 3.52 (t, 2H), 2.68 (m, 2H); MS (m/z) 480. Example 45 N-(3-fluoro-4-memylphenyl)-3'-(trifluoromethyl)-3,6HiihyoVo-2H-lv2'-bipyridine"4- 10 carboxamide The title compound was prepared using the procedure described in Example 40D using 3-fluoro-4-methylaniline instead of 4-tert-butylaniline. *H NMR (300 MHz, CDCI3) δ 8.42 (dd, IH), 7.88 (dd, IH), 7.47 (dd, IH), 7.40 (brs, IH), 7.05-7.15 (m, 2H), 6.98 (dd, IH), 6.76 (sept, IH), 4.05 (q, 2H), 3.51 (t, 2H), 2.66 (m, 2H); MS (m/z) 380. 15 Example 46 N-(4-chlorophenyl)-l-pyrimidin-2-yl-l,2,3,6-tetrahydropyridine-4-carboxamide Example 46A 20 l-pyrimidin-2-yl-l,2,3,6-tetrahydropyridine-4-carboxylicacid 2-Chloropyrimidine (0.570 g, 4.98 mmol) and l,2,3,6-tetrahydro-4-pyridinecarboxylic acid (1.22 g) were combined in water (7 mL) and heated at 90 °C. After 4 hours, the mixture was treated with additional l,2,3,6-tetrahydro-4-pyridinecarboxyIic acid (0.52 g) and stirred overnight The mixture was diluted with water and extracted with CH2CI2. The aqueous 25 layer was acidified with concentrated HCl (pH~3) and extracted with CHCI3. The organic layer was dried (Na2S04), filtered, and the filtrate was concentrated under reduced pressure to provide the title. Example 46B 30 N"(4-chlorophenyl)-l-pyrimidin-2-yl-l,2,3,6-tetrahydropyridine-4-carboxamide l-Pyrimidin-2-yl-l,2,3,6-tetrahydropyridine-4-carboxyIic acid (55.0 mg, 0.27 mmol) and a catalytic amount of DMF were combined in CH2CI2 (1.5 mL) and treated with (COCl)2 48 WO 2(105/007642 PCT/US2004/021836 (0.033 mL, 0.3Smmol). The mixture was stirred for 90 minutes, diluted with toluene (0.5 mL), and concentrated to dryness under reduced pressure. The residue in CH2CI2 (1.5 mL) was treated with pyridine (0.033 mL, 0.41 mmol), catalytic amount of DMAP, and 4-chloroaniline (41.0 mg, 0.32 mmol). The mixture was stirred for 1 hour, diluted with water, 5 and extracted with CH2CI2. The organic phase was dried (Na2S04), filtered, and the filtrate " was concentrated under reduced pressure. The residure was purified by flash chromatography (15% ethyl acetate/ CH2C12) to provide the tide compound. lH NMR (300 MHz, CDCI3) δ 8.35 (d, 2H), 7.51 (d, 2H), 7.39 (brs, IH), 7.31 (d, 2H), 6.77 (sept, IH), 6.54 (t, IH), 4.43 (q, 2H), 4.03 (t, 2H), 2.58 (m, 2H); MS (m/z) 315. 10 Example 47 l-pyrimidin-2-vl-N-(44(trifluoromemyl)thio]phenyl)-l,236-tetrahydropyridine-4- carboxamide The title compound was prepared using the procedure described in Example 46B 15 using 4-[(trifluoromethyl)thio]aniline instead of 4-chloroaniline. lH NMR (300 MHz, CDCI3) δ 8.35 (d, 2H), 7.64 (s, 4H), 7.50 brs, IH), 6.78 (sept, IH), 6.56 (t, IH), 4.45 (q, 2H), 4.05 (t, 2H), 2.59 (m, 2H); MS (m/z) 381. Example 48 20 l-pyrirmdin-2-yl-N-{44(trifluoromemyl)sulfonyllphenyl-123,6-tetrahydropyridme-4- carboxamide The title compound was prepared using the procedure described in Example 46B using 4-[(trifluorometh}'l)sulfonyl]aniline instead of 4-chloroaniline. *H NMR (300 MHz, CDCI3) δS.36 (d, 2H), 8.00 (d, 2H), 7.90 (d, 2H), 7.72 (brs, IH), 6.84 (m, IH), 6.57 (t, IH), 25 4.48 (q, 2H), 4.06 (t, 2H), 2.61 (m, 2H); MS (m/z) 413. The foregoing is merely illustrative and is not intended to limit the invention to the disclosed compounds. Variations and changes which are obvious to one skilled in the art are to be within the scope and nature of the invention which are defined in the appended claims. 30 Example 49 3'-Trifluoromethyl-3,6-dihydro-2H-[l,2]bipyridinyl-4-carboxylie acid (4-tert-butyl-phenyl)- amide 49 WO 2005/007642 PCT/US2004/02J836 Example 49A 3'-Trifluoromethyl-2,3,5,6-tetrahydro-[l,2'lbipyridinyl-4-one A suspension of K2CO3(19.l0 g, 138 mmol), 2-chloro-3-(trifluoromethyl)p)'ridine 5 (11.92 g, 65.7 mmol)) and l,4-Dioxa-8-aza-spiro[4.5]decane (8.85 mL, 69.0 mmol) in DMSO (65 mL) was stirred at 100 °C for 3 hour. Additional l,4-Dioxa-8-aza-spiro[4.5]decane (2.0 mL, 16 mmol) was added and stirred for an additional 2 hour, followed by another aliquot (1.0 mL, 7.8 mmol) and stirring for 1 hour. .The mixture was diluted with Et20 (200 mL), and washed with water (250 mL), washed with brine (100 mL), and the 10 organic layer dried (Na2S04), filtered and concentrated under reduced pressure. The residue was then dissolved in cone HC1 (25 mL), stirred 3 hour, basified with cone NH4OH, extracted with CH2CI2, and dried (Na2S04) and concentrated. Flash chromatographic purification (20 to 40 % Et20/Hex gradient elution) provided the substituted piperidone as a yellow solid (8.35 g, 34.2 mmol, 52%): 'H NMR (300 MHz, CDC3I) 8 8.46 (d, J=4.6 Hz, IH), 7.92 (d, 15 J=7.6Hz, IH), 7.07 (dd, J=4.6, 7.6 Hz, IH), 3.59 (t J=5.9 Hz, 4H), 2.61 (t, J=5.9 Hz, 4H). Example 49B 3'-Trifluoromethyl-3,6-dihydro-2H-[1,2’]bipyridinyl-4-carboxylicacid methyl ester 20 A.solution of the piperidone (8.30 g, 34.0 mmol) in THF (25 mL) was added to a solution of LDA (lithium diisopropylamine) (37.3 mmol) in THF (75 mL) at -78 °C, and stirred 45 minutes. Solid PhNTf2 (14.0 g, 39.1 mmol) was then added, and stirred for 1 hour. The mixture was concentrated under reduced pressure and diluted with 1:1 EtOAchexane, and washed with 1 N NaOH. The organic layer was dried (Na2S04), and filtered through a 25 silica plug, and concentrated under reduced pressure to provide 14.4 g of a red oil. This residue and Et3N (14.2 mL, 102 mmol) and MeOH (7.00 mL, 173 mmol) were dissolved in DMF (100 mL), and saturated with CO (bubbling 15 minutes). Solid PdCl2(PPh3)2 (0.944 g, 1.34 mmol) was added, and the mixture was heated to 80 °C under CO (1 arm) overnight. The mixture was then concentrated under reduced pressure to half volume, diluted with Et20, 30 washed with water, brine, dried (Na2S04), concentrated under reduced pressure and purified by flash chromatography (6% EtOAc/hexane) to provide the methyl ester as a yellow solid (3.90 g, 13.6 mmol, 40%): 'H NMR (300 MHz, CDCI3) δ 8.40 (dd, J=I.7,4.8Hz, IH), 7.87 50 WO 2005/(107642 PCT/US2004/021836 (dd, J=1.7,7.8 Hz, 1H), 7.01 (sept, J=1.7 Hz, 1H), 6.96 (ddd, J=1.0,4.8,7.8 Hz, 1H), 4.03 (q, J=3.0 Hz, 2H), 3.77 (s, 3H), 3.44 (t, J=5.4 Hz, 2H). 5 Example 49C 3'-Trifluoromethyl-3,6-dihydro-2H-ri,2'lbipyridinvl-4-carboxylicacid The ester was dissolved in MeOH (15 mL) and THF (30 mL), and stirred with 1 N NaOH (27 mL) for 2 hour. Additional 1 N NaOH (16 mL) was added and stirred for 1 hour, followed by another aliquot (14.5 mL) for 1 hour. The mixture was then diluted with water, 10 and extracted with CH2CI2. The aqueous layer was then acidified with cone HCI and extracted with CHCI3. The organic layer was dried (Na2S04) and concentrated under reduced pressure to provide 13c a tan solid (3.00 g, 11.0 mmol, 81%): !H NMR (300 MHz, CD3OD) δ 8.45 (m, 1H)> 7.99 (dd, J=2.4, 7.8 Hz, 1H), 7.11 (m, 1H), 7.02 (sept, J=1.7 Hz, 1H), 3.99 (q, J=3.1 Hz, 2H), 3.39 (t, J=5.6 Hz, 2H), 2.49 (m, 2H). 15 Example 49D 3,-Trifluoromethyl-3,6-dihydro-2H-[l,2']bipyridmyl-4-carboxylic acid (4-tert-butyl-phenyl)- amide 20 To a suspension of 3,-trifluoromethyl-3,6-dihydro-2H-[l ^2']bipyridinyl-4-carboxylic acid (60.4 mg, 0.194 mmol) and DMF (cat) in CH2C12 (1 mL) was added (COCl)2 (0.027 mL, 0.31 mmol). The mixture was stirred for 90 minutes, diluted with PhMe (0.5 mL), concentrated under reduced pressure to dryness, and dissolved in CH2CI2 (1.5 mL). To the solution were added pyridine (0.027 mL, 0.33 mmol), DMAP (cat), and 4-tert-butylaniline 25 (0.037 mL, O.023 mmol). The mixture was stirred 1 hour, diluted with water and extracted with CH2C12, dried (Na2S04), and purified by flash chromatography (7% EtOAc/ CH2C12) to provide as a white solid (54.2 mg, 0.123 mmol, 63%): MS (ESI+) ix/z 404 (M+H)+, m/z 402 (M-H)"; 1H NMR (300 MHz, CHLOROFOia^D) 6 ppm 1.31 (s, 9 H), 2.67 (m, 2 H), 3.53 (t, .7=5.4 Hz, 2 H), 4.07 (q, >2.9 Hz, 2 H), 6.76 (m, 1 30 H), 6.98 (dd, .7=7.5,4.4 Hz, 1 H), 7.36 (m, 3 H), 7.48 (m, 2 H), 7.89 (dd, >7.8,1.7 Hz, 1 H), S^Cdd^J-^l^H^lH). Example 50 51 WO 2005/007(542 PCT/US2004/021836 3’-ChIoro-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylic acid (4-azepan-1-yl-phenyl)-amide The title compound was prepared using the procedure described in Example 49D using 4-Azepan-l-yl-phenylamine instead of 4-tert-butylaniline. MS (ESI+) m/z 411 (M+H)+s m/z 409 (M-H)'; IH NMR (500 MHz, CHLOROFORM-D) δ ppm 1.82 (s, 4 H), 2.09 5 (s, 4 H), 2.71 (d, .7=1.6 Hz, 2 H), 3.63 (m, 4 J©, 3.76 ft >5.6 Hz, 2 H), 4.25 (d, ,7=2.8 Hz, 2 H), 6.77 (s, 1 H), 7.01 (dd, >7.8,5.3 Hz, 1 H), 7.46 (d, .7=9.0 Hz, 2 H), 7.74 (d, .7=9.0 Hz, 2 H), 7.87 (dd, >7.8,1.6 Hz, 1 H), 8.20 (dd, 7=5.3,1.6 Hz, 1 H), 8.59 (s, 1 H). 10 Example 51 3'-Chloro-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylic acid(1-tret-butyl-1H-pyrazol-4-yl) amide The title compound was prepared using the procedure described in Example 49D using4- l-tert-butyl-lH-pyrazoI-4-ylamine instead of 4-tert-butylaniline. 'HNMR(300 15 MHz, DMSO-D6) δ ppm 1.50 (s, 9 H), 2.53 (s, 2 H), 3.45 ft 7=5.6 Hz, 2 H), 3.99 (q, .7=2.7 Hz, 2 H), 6.74 (s, 1 H), 7.00 (dd, 7=7.8,4.7 Hz, 1 H), 7.53 (s, 1 H), 7.82 (dd, 7=7.8,1.7 Hz, 1 H), 7.99 (s, 1 H), 8.22 (m, 1 H), 9.85 (s; 1 H). 20 Example 52 l-Pyrimidm-2-yl-l;23>6-tetrahydro-pyridine-carboxylicacid(4-tert-butyl-phenyl)-amide Example 52A l-Pyrimidin-2-yl-1,2,3,6-terrahydro-pyridine-4'carboxylicacid 25 A mixture of 2-chloropyrimidine (0.570 g, 4.98 mmol), and isoguvacine, sodium salt (1.2 g, 8.2 mmol) in water (7 mL) was heated to 90 °C and stirred for 4 hour. Additional isoguvacine, sodium salt (0.52 g, 3.3 mmol) was then added and stirred overnight. The mixture was diluted with water and extracted with CH2CI2. The aqueous layer was acidified with cone HC1 (pH~3) and extracted with CHC13, The organic layer was dried (Na2S04), 30 filtered and concentrated under reduced pressure to provide l-Pyrirnidin-2-yl-l,2,3,6- tetrahydro-pyridine-4-carboxylic acid a white solid (0.564 g, 2.75 mmol, 55%): lH NMR 52 WO 2005/007642 PCT/US2004/021836 (300 MHz, CD3OD) 6 8.43 (d, J=4.8 Hz, 2H), 7.02 (sept, J=1.7 Hz, IH), 6.74 ft J=4.8 Hz, IH), 439 (q, J=3.0 Hz, 2H), 3.97 ft J=5.8 Hz, 2H), 2.49 (m, 2H). 5 Example 52B l-Pyriirudin-2-yl-l,23,6-tetrahydro-pyridine-4-carboxylic acid(4-tert-butyl-phenyl)-amide To a suspension of l-Pyi±nidin-2-yl-l,2,3)6-tetrahydro-pvridine-4-carboxylic acid (60.4 mg, 0.194 mmol) and DMF (cat) in CH2C12 (1 mL) was added (COCI)2 (0.027 mL, 0.31 mmol). The mixture was stirred for 90 minutes, diluted with PhMe (0.5 mL), concentrated 10 under reduced pressure to dryness, and dissolved in CH2CI2 (1 -5 mL). To the solution were added pyridine (0.027 mL, 0.33 mmol), DMAP (cat), and 4-tert-butylaniline (0.037 mL, 0.023 mmol). The mixture was stirred 1 hour, diluted with water and extracted with CH2CI2, dried (Na2S04), and purified by flash chromatography (7% EtOAc/ CH2CI2) to provide 1-Pyrimidin-2-yl-l,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-te?-/-butyl-phenyl)-amide as a 15 white solid (54.2 mg, 0.123 mmol 63%): MS (ESI+) m/z 337 (M+H)+? m/z 334 (M-H)'; IH NMR (300 MHz, CHLOROFOm-D) δ ppm 1.31 (s, 9 H), 2.59 (m, 2 H), 4.04 ft ^5.6 Hz, 2 H), 4.44 (q, J=3.1 Hz, 2 H), 6.54 ft J=4.7 Hz, 1 H), 6.75 (m, 1 H), 7.36 (m, 3 H), 7.47 (m, 2 H), 8.35 (d, .7=4.7 Hz, 2 H). 20 Example 53 l-Pyrimidin-2-yl-l .2,3?6-tetrahydro-pyridine-4-carboxylic acid (4-chloro-phenyl)-amide The title compound was prepared using the procedure described in Example 52B using 4-chloro-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 315 (M+H)+; IH NMR 25 (300 MHz, CHLOROFORM-D) δ ppm 2.58 (m, 2 H), 4.03 ft .7=5.6 Hz, 2 H), 4.44 (q, J=3.1 Hz, 2 H), 6.54 ft J=4.1 Hz, 1 H), 6.77 (m, 1 H), 7.30 (d, .7=9.2 Hz, 2 H), 7.39 (s, I H), 7.52 (d, .7=8.8 Hz, 2 H), 8.35 (d, 7=4.7 Hz, 2 H). 30 Example 54 l-Pyrirm'dm-2-yl-1.23,6-tetrahydro-pyridtne-4-carboxylicacid(4-trifluoromemyoxy phenyl)-amide 53 WO 2005/007642 PCT/US2004/02183 The title compound was prepared using the procedure described in Example 52B using 4-trifluoromethoxy-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 365 (M+H)+, m/z 363 (M-H)"; IH NMR (300 MHz, CHLOROFORAf-D) 6 ppm 2.59 (m, 2 H), 4.04 (t, 7=5.6 Hz, 2 H), 4.44 (q, 7=3.1 Hz, 2 H), 6.55 (t, 7=4.7 Hz, 1 H), 6.77 (m, 1 H), 7.19 (d, 7=9.2 5 Hz, 2 H), 7.44 (s, 1 H), 7.59 (d, 7-9.2 Hz, 2 H), 8.35 (d, >4.7 Hz, 2 H). Example 55 l-Pyrimidin-2-yl-l,2,3,6-tetrahyfro-pyridme-4-carboxylic acid(4-trifluoromethylsulfanyl- 10 phenyl)-amide The title compound was prepared using the procedure described in Example 52B using 4- trifluoromethylsulfanyl-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 381 (M+H)+, m/z 379 (M-H)*; IH NMR (300 MHz, DMSO-D6) δ ppm 2.47 (s, 2 H), 3.93 (t, 7=5.8 Hz, 2 H), 4.38 (q, 7=2.7 Hz, 2 H), 6.69 (t, 7=4.7 Hz, 1 H), 6.84 (m, I H), 7.66 (d, 7=8.8 15 Hz, 2 H), 7.86 (d, 7=8.8 Hz, 2 H), 8.42 (d, 7=5.1 Hz, 2 H), 10.09 (s, 1 H). Example 56 1 -Pyrimidm-2-yl-l ,2,3.6-tetrahydro-pyridine-4-carboxylic acid (4-trifluoromethanesuIfony]- 20 phenyl)-amide The title compound was prepared using the procedure described in Example 52B using 4- trifluoromethylsulfonyl-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 413 (M+H)+, m/z 411 (M-H)'; IH NMR (300 MHz, CHLOROFOUd-D) δ ppm 2.61 (s, 2 H), 4.06 (t, 7=5.6 Hz, 2 H), 4.49 (q, 7=2.9 Hz, 2 H), 6.57 (t, 7=4.7 Hz, 1 H), 6.84 (s, 1 H), 7.72 (s, 1 25 H), 7.89 (d, 7=8.8 Hz, 2 H), 8.01 (d, 7=8.8 Hz, 2 H), 8.36 (d, 7=4.7 Hz, 2 H). Example 57 3*-CliJoro-3,6-dihydro-2ff-rL2'1bipvridinyl-4-carboxylicacid(,4-bromo-3-fluoro-phenyl)- 30 amide The title compound was prepared using the procedure described in Example 52B using 4-bromo-3-£luoro-aniIine instead of 4-ter-butylaniline. MS (ESI+) m/z 411 (M+H)+, 54 WO 2005/007642 PCT/US2004/021836 '*z 409 (M-H)"; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.55 (d, 7=1 .7 Hz, 2 H), 3.45 (t, 7=5.6 Hz, 2 H), 4.02 (q, J=2.9 Hz, 2 H), 6.82 (s, 1 H), 7.01 (dd, 7=7:8,4.7 Hz, 1 H), 7.47 (dd, 7=8.8,2.4 Hz, 1 H), 7.63 (t, 7=8.8 Hz, 1 H), 7.82 (d, .7=1.4 Hz, 1 H), 7.85 (dd, 7=4.9, 1.9 Hz, 1 H), 8.22 (dd, 7=4.7,1.7 Hz, 1 H), 10.05 (s, 1 H). 5 Example 58 3,-Chloro-3,6-dihydro-2H-[1,2]bipyridiyl-4-carboxylicacid(4-bromo-3-methyl-phenyl)- amide 10 The title compound was prepared using the procedure described in Example 49D using 4- bromo-3-methyl-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 407 (M+H)+, m/z 405 (M-H)'; 1H NMR (300 MHz, DMS0-D6) δ ppm 2.32 (s, 3 H), 2.56 (s, 2 H), 3.44 (t, 7=5.4 Hz, 2 H), 4.01 (q, 7=2.7 Hz, 2 H), 6.79 (s, 1 H), 7.00 (dd, 7=7.8,4.7 Hz, 1 H), 7.49 (s, 2 H), 7.71 (s, 1 H), 7.83 (dd, 7=7.6,1.5 Hz, 1 H), 8.22 (dd, 7=4.7,1.7 Hz, 1 H), 9.78 (s, 1 H). 15 Example 59 3 '-Trifluoromethyl-3,6-dihydro-2H-[1,2’] bipyridinyI-4-carboxylic acid (4-chloro-phenyl)- amide 20 The title compound was prepared using the procedure described in Example 49D using 4- chloro-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 382 (M+H)+, m/z 380 (M-H)*; 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 2.66 (m, 2 H), 3.51 (t, 7=5.6 Hz, 2 H), 4.06 (q, 7=3.1 Hz, 2 H), 6.77 (m, 1 H), 6.99 (dd, >8,1,4.4 Hz, 1 H), 7.30 (m, 2 H), 7.43 (s, 1 H), 7.52 (m, 2 H), 7.89 (dd, 7=7.8, 1.7 Hz, 1 H), 8.42 (dd, 7=4.7, 1.4 Hz, 1 H). 25 Example 60 3'-Trifluoromethyl-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylicacid(4-trifluoromethoxy- phenyl)-amide 30 The title compound was prepared using the procedure described in Example 49D using 4- trifluoromethoxy-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 432 (M+H)+, m/z 430 (M-H)-; 1H NMR (300 MHz, CHLOROFOM4-D) δ ppm 2.67 (m, 2 H), 3.53 (t, 55 WO 2005/007642 PCT/US2004/021836 .7=5.4 Hz, 2 H), 4.08 (q, 7==2.7 Hz, 2 H), 6.79 (s, 1 H), 7.00 (dd, 7=7.8,4.7 Hz, 1 H), 7.20 (d, 7=8.1 Hz, 2 H), 7.48 (s, 1 H), 7.60 (d, 7=9.2 Hz, 2 H), 7.90 (dd, 7=7.8,1.7 Hz, 1 H), 8.43 (dd, 7=4.9,1.2 Hz, 1H). 5 Example 61 3,-Trifluoromethyl-3,6-dihydro-2H-[l,2,]bipyridinyl-4-carboxcylicacid('4-trifluoromethylsulfanyl-phenyl)-amide The title compound was prepared using the procedure described in Example 49D 10 using 4- trifluoromethylsulfanyl-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 448 (M+H)+, m/z 446 (M-H)"; 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 2.66 (m, 2 H), 3.52 (t, 7=5.6 Hz, 2 H), 4.08 (q, 7=2.8 Hz, 2 H), 6.79 (m, 1 H), 7.01 (dd, 7=7.8,4.7 Hz, 1 H), 7.52 (s, 1 H), 7.64 (d, 7=2.4 Hz, 4 H), 7.90 (dd, 7=7.8,1.7 Hz, 1 H), 8.43 (d, 7=3.4 Hz, 1 H). 15 Example 62 3 '-Chloro-3,6-dihydro-2H-[1 ,2]bipyridinyl-4-carboxylic acid (4-bromo-3-chloro-phenyl)- amide The title compound was prepared using the procedure described in Example 49D 20 using 4-bromo-3-chloro-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 427 (M+H)+, m/z 425 (M-H)-; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.55 (m, 2 H), 3.45 (t, 7=5.6 Hz, 2 H), 4.02 (q, 7=2.7 Hz, 2 H), 6.83 (m, 1 H), 7.01 (dd, 7=7.8,4.7 Hz, 1 H), 7.60 (m, 1 H), 7.70 (m, 1 H), 7.83 (dd, 7=7.8,1.7 Hz, 1 H), 8.07 (d, 7=2.4 Hz, 1 H), 8.22 (dd, 7=4.7,1.7 Hz, 1 H), 10.00 (s,lH). Example 63 3 '-Trifluoromethyl-3,6-dihydro-2H-[ 1,2]'Ibipyridinyl-4-carboxylic acid (4-azepan-l-yl- 30 phenyl)-amide The title compound was prepared using the procedure described in Example 49D using 4-azepan-l-yI -aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 445 (M+H)+, m/z 56 /O 2005/007642 PCT7US2004/02I836 (M-H)-; IH NMR (300 MHz, CHLOROFORM-D) δ ppm 1.54 (m, 4 H), 1.78 (s, 4 H), 2.65 (m, 2 H), 3.44 (s, 4 H), 3.52 (t, 7=5.4 Hz, 2 H), 4.05 (d, 7=2.4 Hz, 2 H), 6.65 (d, 7=5.8 Hz, 2 H), 6.73 (s, 1 H), 6.97 (dd, 7=7.8,4.7 Hz, 1 H), 7.22 (m, 1 H), 7.35 (d, 7=8.5 Hz, 2 H), 7.87 (dd, 7=7.8, 2.0 Hz, 1 H), 8.41 (dd, .7=4.7,1.7 Hz, 1 H). 5 Example 64 3,-Chloro-3,6-dihydro-2H-[l,2]bipyridinyl-4-carboxylicacid(4-bromo-3-trifIuoromethyl- phenyl)-amide 10 The title compound was prepared using the procedure described in Example 49D using 4-bromo-3-trifluoromethyl-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 461 (M+H)+, m/z 459 (M-H)*; IH NMR (300 MHz, DMSO-D6) δ ppm 2.56 (br. s, 2 H), 3.46 (t, 7=5.6 Hz, 2 H), 4.03 (q, 7=2.7 Hz, 2 H), 6.86 (m, 1 H), 7.01 (dd, 7=7.8,4.7 Hz, 1 H), 7.82 (d, 7=1.7 Hz, 1 H), 7.S4 (m, 1 H), 7.95 (dd, 7=8.8,2.4 Hz, 1 H), 8.23 (dd, J=4.7,1.7 Hz, 1 H), 15 8.28 (d, 7-2.4 Hz, 1 H), 10.14 (s, 1 H). Example 65 3’-Chloro-3,6-dihydro-2H-[l,2]bipyridinyl-4-carboxylicacid(4-chioro-3-fluor6-phenyl)- 20 amide The title compound was prepared using the procedure described in Example 49D using 4-chloro-3-fluoro-3niline instead of 4-ter-butylaniline. MS (ESI+) m/z 365 (M+H)+, m/z 363 (M-H)'; IH NMR (300 MHz, DMSO-D6) δ ppm 2.55 (br. s, 2 H), 4.02 (q, 7=2.9 Hz, 2 H), 6.82 (m, 1 H), 7.01 (dd, 7=7.8,4.7 Hz, 1 H), 7.52 (m, 2 H), 7.84 (m, 2 H), 8.22 (dd, 25 7=4.7,1.7 Hz, 1 H), 10.05 (s, 1 H). Example 66 3'-Chloro-3,6-dihydro-2H-[l,2]lbipyridinyl-4-carboxylic acid (3,4-dichloro-phenyl)-amide 30 The title compound was prepared using the procedure described in Example 49D using 3,4-dichloro-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 381 (M+H)+; IH NMR (300 MHz, DMSO-D6) δ ppm 2.55 (m, 2 H), 3.45 (t, 7=5.4 Hz, 2 H), 4.02 (q, 7=2.8 Hz, 57 WO 2005/007642 PCT/US2004/02I836 2 H), 6.82 (m, 1 H), 7.01 (dd, .7=7.8,4.7 Hz, 1 H), 7.57 (d, 7=8.8 Hz, 1 H), 7.67 (dd, 7=8.8, 2.4 Hz, 1 H), 7.83 (dd, 7=7.8,1.7 Hz, 1 H), 8.07 (d, 7=2.4 Hz, 1 H), 8.22 (dd, 7=4.7,1.7 Hz, 1 H)? 10.01 (s, 1 H). 5 Example 67 3'-Chloro-3,6-dihydro-2H-[1 ,2]bipyridinyl-4-carboxylic acid (4-chloro-3-methyl-phenyl)- amide The title compound was prepared using the procedure described in Example 49D 10 using 4-chIoro-3-methyl-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 361 (M+H)+, m/z 360 (M-H)"; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.30 (s, 3 H), 2.55 (m, 2 H), 3.46 (t, 7=5.4 Hz, 2 H), 4.01 (q, 7=2.7 Hz, 2 H), 6.79 (m, 1 H), 7.00 (dd, 7=7.8,4.7 Hz, 1 H), 7.33 (d, 7=8.8 Hz, 1 H), 7.55 (dd, 7=8.6,2.5 Hz, 1 H), 7.70 (d, 7=2.7 Hz, 1 H), 7.83 (dd, 7=7.8,1.4 Hz, 1 H), 8.22 (dd, 7=4.7, 1.7 Hz, 1 H), 9.78 (s, 1 H). 15 Example 68 3'-Chloro-3,6-dihydro-2H-[112]bipyridinyl-4-carboxylicacid(4-chloro-3-trifluoromethyl- phenyl)-amide 20 The title compound was prepared using the procedure described in Example 49D using 4-chloro-3-trifluoromethyl-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 415 (M+H)+, m/z 413 (M-H)"; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.56 (m, 2 H), 3.46 (t, 7=5.6 Hz, 2 H), 4.03 (q, 7=2.7 Hz, 2 H), 6.86 (m, 1 H), 7.01 (dd, 7=7.8,4.7 Hz, 1 H), 7.67 (d, 7=8.8 Hz, 1 H), 7.83 (dd, 7=7.8,1.7 Hz, 1 H), 8.02 (dd, 7=8.8,2.7 Hz, 1 H), 8.22 (dd, 7=4.6, 25 1.5 Hz, 1 H), 8.28 (d, 7=2.7 Hz, 1 H), 10.14 (s, 1 H). Example 69 3,-Chloro-3,6-dihydro-2H-[1,2]bipyridmyl-4-carboxyhcacid(4-difluoromethyoxy-phenyl)- 30 amide The title compound was prepared using the procedure described in Example 49D using 4- difluoromethyoxy-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 379 (M+H)+, 58 WO 2005/007642 PCT/US2004/021836 m/z 3V (M-H)"; 1HNMR (300 MHz, DMSO-D6) δ ppm 2.56 (m, 2 H), 3.45 (1,7=5.8 Hz, 2 H), 4.02 (q, 7=2.7 Hz, 2 H), 6.79 (m, 1 H), 7.00 (dd, 7=7.8,4.7 Hz, 1 H), 7.13 (d, 7=8.1 Hz, 2 H), 7.15 (t, 7=45 Hz, 1H), 7.72 (d, 7=9.2 Hz, 2 H), 7.83 (dd, 7=7.8,1.7 Hz, 1 H), 8.22 (dd, 7=4.7,1.4 Hz, 1H), 9.82 (s, 1 H). 5 Example 70 3’-Chloro-3,6-dihydro-2H-[l,2]bipyridinyl-4-carboxylicacid[4-(1,1.2.2-tetrafluoro- ethoxy)-phenyl]-amide 10 The title compound was prepared using the procedure described in Example 49D using 4-(l,l,2,2-tetrafluoro-ethoxy)-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 429 (M+H)+, m/z 427 (M-H)"; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.56 (m, 2 H), 3.46 (t, 7=5.6 Hz, 2 H), 4.02 (q, 7=2.7 Hz, 2 H), 6.79 (m, 1 H), 6.80 (tt, 7=52, 3.1 Hz, 1 H), 7.01 (dd, 7=7.6,4.6 Hz, 1 H)s 7123 (d, 7=9.2 Hz, 2 H), 7.78 (d, 7=9.2 Hz, 2 H), 7.83 (dd, 7=7.8,1.7 Hz, 15 1 H), 8.23 (dd, 7=4.7, 1.7 Hz, 1 H), 9.90 (s, 1 H). Example 71 3,-Chloro-3,6-dihydro-2H"[l,2]bipyridinyl-4-carboxylicacid(3-chloro-4-methyl-phenyl)- 20 amide The title compound was prepared using the procedure described in Example 49D using 3-chloro-4-methyl-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 361 (M+H)+, m/z 360 (M-H)"; 1H NMR (300 MHz, DMS0-D6) δ ppm 2.28 (s, 3 H), 2.55 (m, 2 H), 3.45 (t, 7=5.6 Hz, 2 H), 4.01 (q, 7=2.8 Hz, 2 H), 6.79 (m, 1 H), 7.00 (dd, 7=7.8,4.7 Hz, 1 H), 7.27 (d, 25 7=8.5 Hz, 1 H), 7.52 (dd, 7=8.3,2.2 Hz, 1 H), 7.83 (dd, 7-7.5,1.4 Hz, 1 H), 7.86 (d, 7=2.0 Hz, 1 H), 8.22 (dd, 7=4.7,1.7 Hz, 1 H), 9.81 (s, 1 H). Example 72 30 3’-Chloro-3,6-dihydro-2H,-[l ,2']bipyridinyl-4-carboxylic acid (3-bromo-4-methyl-phenyl)- amide 59 WO 2005/007642 PCT/US2004/021836 The title compound was prepared using the procedure described in Example 49D using 3-bromo-4-methyl-aniIine instead of 4-ter-butylaniline. MS (ESI+) m/z 407 (M+H)+, m/z 405 (M-H)'; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.29 (s, 3 H), 2.55 (m, 2 H), 3.45 (t, 7=5.4 Hz, 2 H), 4.01 (q, J=2.7 Hz, 2 H), 6.79 (m, 1 H), 7.00 (dd, 7=7.8,4.7 Hz, 1 H), 7.28 (d, 5 7=9.2 Hz, 1 H), 7.58 (dd, 7=8.3,22 Hz, 1 H), 7.82 (dd, 7=7.8,1.4 Hz, 1 H), 8.03 (d, 7=2.0 Hz, 1 H), 8.22 (dd, 7=4.7,1.4 Hz, 1 H), 9.80 (s, 1 H). Example 73 10 3,-Chloro-3,6-dihydro-2H-[1,2,]bipyridiny-4-carboxylicacid(4-methyl-3-trifluoromemyl- phenyl)-amide The title compound was prepared using the procedure described in Example 49D using 3-trifluoromethyl-4-methyl-amline instead of 4-ter-butylaniline. MS (ESI+) m/z 396 (M+H)+, m/z 394 (M-H)'; 1H NMR (300 MHz, DMS0-D6) δ ppm 2.39 (d, 7=1.7 Hz, 3 H), 15 2.56 (m, 2 H), 3.46 (t, 7=5.6 Hz, 2 H), 4.02 (q, 7=2.7 Hz, 2 H), 6.83 (m, 1 H), 7.00 (dd, 7=7.8, 4.7 Hz, 1 H), 7.37 (d, 7=8.5 Hz, 1 H), 7.84 (m, 2 H), 8.09 (d, 7=2.4 Hz, 1 H), 8.22 (dd, 7=4.6, 1.5Hz,lH),9.94(s,lH). 20 Example 74 3'-ChIoro-3,6-dihydro-2.H-[l,2']bipyridinyl-4-carboxylic acid (5-fluoro-pyridin-2-yl)-amide The title compound was prepared using the procedure described in Example 49D using 5-fluoro-pyridin-2-ylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 330 (M-H)* (20%) m/z 212 (M-I20)" (100%); 1H NMR (300 MHz, DMSO-D6) δ ppm 2.57 (m, 2 H), 4.00 25 (q, 7=2.8 Hz, 3 H), 6.92 (m, 1 H), 7.00 (dd,7=7.8,4.7 Hz, 1 H), 7.75 (m, 1 H), 7.82 (dd, 7=7.8,1.7 Hz, 1 H), 8.11 (dd, 7=9.3,4.2 Hz, 1 H), 8.22 (dd, 7=4.7,1.7 Hz, 1 H), 8.35 (d, 7=3.4 Hz, 1H), 10.30 (s, 1 H). 30 Example 75 3’-Chloro-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylicacid ("5-chloro-pyridin-2-yl)-amide 60 WO 2005/007642 PCT/US2004/021836 The title compound was prepared using the procedure described in Example 49D using 5-chloro-pyridin-2-ylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 348 (M+H)+, m/z 346 (M-H)' (80%) m/z212 (M-137)" (100%); 1HNMR (300 MHz, DMS0-D6) δ ppm 2.57 (m, 2 H), 3.44 (t, 7=5.4 Hz, 2 H), 4.00 (q, .7=2.9 Hz, 2 H), 6.94 (m, 1 H), 7.00 (dd, 7=7.8, 5 4.7 Hz, 1 H), 7.82 (dd, 7=7.8,1.7 Hz, 1 H), 7.91 (dd, 7=9.0,2.9 Hz, 1 H), 8.11 (d, 7=0.7 Hz, 1 H), 8.22 (dd, 7=4.7,1.4 Hz, 1 H), 8.40 (dd, 7=2.5,0.8 Hz, 1 H), 10.39 (s, 1 H). Example 76 10 3,-Chloro-3,6-dihydro-2H[l,2]bipyridinyl-4-carboxylicacid(5-bromo-pyridin-2-yl)-amide The title compound was prepared using the procedure described in Example 49D using 5-bromo-pyridin-2-ylamine instead of 4-ter-butyIaniline. MS (ESI+) m/z 395 (M+H)+ (60%), m/z 392 (M-H)+ (100%), m/z 392 (M-H)*; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.56 (m, 2 H), 3.44 (t 7=5.6 Hz, 2 H), 4.00 (q, 7=2.7 Hz, 2 H), 6.95 (m, 1 H), 7.00 (dd, 7=7.8, 15 4.7 Hz, 1 H), 7.82 (dd, 7=7.8,1.7 Hz, 1 H), 8.04 (m, 2 H), 8,22 (dd, 7=4.7, 1.7 Hz, 1 H), 8.47 (dd, 7=2.4,0.7 Hz, 1 H), 10.39 (s, 1 H). Example 77 20 3' -Chloro-3,6-dihydro-2H [1,2']bipyridinyl-4-carboxylic acid (5-iodo-pyridin-2-yl)-amide The title compound was prepared using the procedure described in Example 49D using 5-iodo-pyridin-2-ylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 441 (M+H)+ (95%), m/z 436 (M-4)+ (100%), m/z 438 (M-H)* (25%), m/z 211 (M-229)* (100%); 1H NMR (300 MHz, DMSO-D6) δ ppm 2.56 (m, 2 H), 3.99 (q, 7=2.7 Hz, 2 H), 6.94 (m, 1 H), 7.00 (dd, 25 7=7.6,4.6 Hz, 1 H), 7.82 (dd, 7=7.8,1.7 Hz, 1 H), 7.97 (dd, 7=8.8,1.0 Hz, 1 H), 8.12 (dd, 7=8.6,2.2 Hz, 1 H), 8.21 (dd, 7=4.6,1.5 Hz, 1 H), 8.56 (dd, 7=2.4,0.7 Hz, 1 H), 10.33 (s, 1 H). 30 Example 78 3,-Chloro-3,6-dihydro-2H-[l,2,lbipyridinyl-4-carboxylicacid(4-trifluoromethylsulfanyl- phenyl)-amide 61 WO 2005/007642 PCT/US2004/021836 The title compound was prepared using the procedure described in Example 49D using 5-fluoro-pyridin-2-ylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 413 (M+H)+, m/z 411 (M-H)"; 1HNMR (400 MHz, DMSO-D6) δ ppm 2.57 (m, 2 H), 3.46 (t, 7=5.5 Hz, 2 H), 4.03 (q, 7=2.9 Hz, 2 H), 6.84 (m, 1 H), 7.00 (dd, 7=7.7,4.6 Hz, 1 H), 7.66 (d,7=8.6 Hz, 2 5 H), 7.82 (dd, 7=7.8,1.7 Hz, 1 H), 7.87 (m, 2 H), 8.23 (dd, 7=4.8,1.7 Hz, 1 H), 10.04 (s, 1 H). Example 79 3'-Chloro-3,6-dmydro-2ff-rijnbipyridinyl-4-carboxyilc acid(3-fluoro-4-trifluoromethyl-phenyl)-amide 10 The title compound was prepared using the procedure described in Example 49D using 3-fluoro-4-trifluoromethyI-aniline instead of 4-ter-butylaniline. MS (DCI+) m/z 400 (M+H)+; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.57 (m, 2 H), 3.46 (t, 7=5.4 Hz, 2 H), 4.04 (q, 7=3.1 Hz, 2 H), 6.88 (m51 H), 7.01 (dd, 7=7.6,4.6 Hz, 1 H), 7.70 (m, 2 H), 7.83 (dd, 15 7=7.8, 1.7 Hz, 1 H), 7.91 (d,7=13.6 Hz, 1 H), 8.23 (dd, 7=4.7, 1.4 Hz, 1 H), 10.28 (s, 1 H). Example 80 3'-Crdoro-3,6-dihydro-2H-[l,2]bipyridinyl-4-carboxylicacid(4-bromo-2-chloro-phenyl') 20 amide The title compound was prepared using the procedure described in Example 49D using 2-chloro-4-broroo-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 427 (M+H)+ (80%), m/z 459 (M+32)+ (100%), m/z 426 (M-H)' (90%), m/z 305 (M-122)- (100%); 1H NMR (400 MHz, DMSO-D6) δppm 2.56 (m, 2 H), 3.46 (t, 7=5.5 Hz, 2 H), 4.03 (q, 7=2.8 Hz, 25 2 H), 6.89 (m, 1 H), 7.00 (dd, 7=7.8,4.8 Hz, 1 H), 7.55 (m, 2 H), 7.79 (d, 7=1.8 Hz, 1 H), 7.82 (dd, 7=7.7,1.8 Hz, 1 H), 8.22 (dd, 7-4.8,1.4 Hz, 1 H), 9.45 (s, 1 H). Example 81 30 3'-Chloro-3,6-dihydro-2H"-[l,2']bipyridinyl-4-carboxylicacid(4-bromo-2-fluoro-phenyl)- amide \'0 2005/007642 PCT/US20O4/O21836 The title compound was prepared using the procedure described in Example 49D using 2-fluoro-4-bromo-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 410 (M+H)+ (80%), m/z 407 (M-3)+ (100%), m/z 409 (M-H)*; 1H NMR (400 MHz, DMSO-D6) δ ppm 2.55 (m, 2 H), 3.46 (t, 7=5.5 Hz, 2 H), 4.02 (q, 7-3.0 Hz, 2 H), 6.86 (m, 1 H), 7.00 (dd, 7=7.8, 5 4.8 Hz, 1 H), 7.40 (ddr7=8.6,1.2 Hz, 1 H), 7.54 (t, 7=8.4 Hz, 1 H), 7.59 (dd, 7=10.1,2.1 Hz, 1 H), 7.82 (dd, 7=7.8,1.7 Hz, 1 H), 8.22 (dd, 7=4.6,1.5 Hz, 1 H), 9.60 (s, 1 H). Example 82 10 3' -Chloro-3,6-dihy dro-2ff- [ 1,2 ']bipyridiny1-4-carboxylic acid (4-bromo-2-methyl-phenyl)- amide The title compound was prepared using the procedure described in Example 49D using 2-methyI -4-bromo-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 407 (M+H) , ni/z 405 (M-H)'; 1HNMR (400 MHz, DMSO-D6) δ ppm 2.19 (s, 3 H), 2.57 (m, 2 H), 3.46 (t 15 7=5.5 Hz, 2 H), 4.02 (q, 7=2.9 Hz, 2 H), 6.83 (m, 1 H), 7.00 (dd, 7=7.8,4.8 Hz, 1 H), 7.27 (d, 7=8.6 Hz, 1 H), 7.36 (m, 1 H), 7.46 (d, 7=1.5 Hz, 1 H), 7.82 (dd, 7=7.8,1.7 Hz, 1 H), 8.22 (dd, 7=4.8,1.7 Hz, 1 H), 9.30 (s, 1 H). 20 Example 83 3’-Chloro-3,6-dihydro-2H-[l,2']bipyridinyl-4-carboxylicacid(2-fluoro-4-iodo-phenyl)- amide The title compound was prepared using the procedure described in Example 49D using 2-fluoro-4-iodo-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 457 (M+H)+ 25 (80%), m/z 453 (M-4)+ (100%), m/z 455 (M-H)"; 1H NMR (400 MHz, DMSO-D6) δ ppm 2.54 (m, 2 H), 3.46 (t, 7=5.5 Hz, 2 H), 4.01 (q, 7=2.8 Hz, 2 H), 6.85 (m, 1 H), 7.00 (dd, 7=7.7, 4.6 Hz, 1 H), 7.38 (t, 7=8.3 Hz, 1 H), 7.54 (dd, 7=8.3, 1.2 Hz, 1 H), 7.68 (dd, 7=10.0, 2.0 Hz, 1 H), 7.82 (dd, 7=8.0,1.5 Hz, 1 H), 8.22 (dd, 7=4.6, 1.5 Hz, 1 H), 9.57 (s, 1 H). 30 Example 84 l'-Chloro-3,6-dihydro-2H-[1.2]bipyridiriyl-4-carboxylicacid(4-chloro-2-trifIuoromethyl- 63 WO 2005/007642 PCT/US2004/021836 phenyl)-amide The title compound was prepared using the procedure described in Example 49D using 2-trifluoromethyl-4-chloro-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 417 (M+H)4 (75%), m/z 230 (M-1 %Sf (100%), m/z 414 (M-H)-; IH NMR (400 MHz, DMSO-D6) 5 δ ppm 2.54 (m, 2 H), 3.46 (t, 7=5.4 Hz, 2 H), 4.02 (q, 7=2.8 Hz, 2 H), 6.83 (m, 1 H), 7.00 (dd, 7=7.8,4.8 Hz, 1 H), 7.52 (d, 7=8.3 Hz, 1 H), 778 (dd,7=8.6,2.5 Hz, 1 H), 7.82 (m, 2 H), 8.22 (dd, .7=4.8,1.7 Hz, 1 H), 9.57 (s, 1 H). 10 Example 85 3>-Chloro-3,6-dihydro-2H'-[l,2,]bipyridinyl-4-carboxylicacid(4-chloro-2-fluoro-phenyl)- amide The title compound was prepared using the procedure described in Example 49D using 2-fluoro-4-chloro-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 366 (M+H)+, 15 m/z 365 (M-H)' (80%), m/z 363 (M-3)* (100%); IH NMR (400 MHz, DMSO-D6) δ ppm 2.55 (m, 2 H), 3.46 (t, 7=5.5 Hz, 2 H), 4.02 (q, 7=2.8 Hz, 2 H), 6.86 (m, 1 H), 7.00 (dd, 7=7.7,4.6 Hz, 1 H), 7.28 (m, 1 H), 7.49 (dd, 7=10.4,2.5 Hz, 1 H), 7.58 (t, 7=8.4 Hz, 1 H), 7.82 (dd, 7=7.8, 1.7 Hz, 1 H), 8.22 (d, 7=1.5 Hz, 1 H), 9.60 (s, 1 H). 20 Example 86 3'-Chloro-3,6-dihydro-2H"-[1,2']bipyridinyl-4-carboxyIicacid(2,2-difluoro- benzo[l ,3]dioxol-5-yl)-amide The title compound was prepared using the procedure described in Example 49D 25 using 2,2-difluoro-benzo[l,3]dioxol-5-yl amine instead of 4-ter-butylaniline. MS (ESI+) m/z 216 (M-177)+ (100%), m/z 391 (M-H)*; IH NMR (300 MHz, DMSO-D6) δ ppm 2.56 (m, 2 H), 3.46 (t, 7=5.6 Hz, 2 H), 4.02 (q, 7=2.7 Hz, 2 H), 6.80 (m, 1 H), 7.00 (dd, 7=7.8,4.7 Hz, 1 H), 7.35 (d, 7=8.8 Hz, 1 H), 7.42 (dd, 7=8.8,2.0 Hz, 1 H), 7.83 (m, 2 H), 8.22 (dd, 7=4.7,1.7 Hz, 1 H), 9.94 (s, 1 H). 30 Example 87 64 -WO 2005/007642 PCT/US2004/02183G 3'-Chloro-3,6-dihydro-2.tf-T^2'1bipyridinyl-4-carboxylic acid (3,4-dimethyl-phenylVamide The title compound was prepared using the procedure described in Example 49D using 3,4-dimethyl-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 342 (M+H)+; IH NMR (300 MHz., DMSO-D6) δ ppm 2.17 (s, 3 H), 2.19 (s, 3 H), 2.55 (m, 2 H), 3.46 (t, 7=5.4 5 Hz, 2 H), 4.00 (q, 7=2.7 Hz, 2 H), 6.75 (m, 1 H), 7.00 (dd, 7=7-8,4.7 Hz, 1 H), 7.04 (m, 1 H), 7.39 (dd, 7=8.0,2.2 Hz, 1 H), 7.46 (d, 7=2.0 Hz, 1 H), 7.82 (dd,7=7.8,1.7 Hz, 1 H), 8.22 (dd, 7=4.6,1.5 Hz, 1 H), 9.56 (s, 1 H). 10 Example 88 3,-C.hloro-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylic acid (6-trifluoromemyl-pyridin-3- yl)-amide The title compound was prepared using the procedure described in Example 49D using 6-trifluoromethyl-pyridin-3-yIamine instead of 4-ter-butylaniline. MS (ESI+) m/z 382 15 (M+H)+, m/z 380 (M-H)'; IH NMR (300 MHz, DMSO-DS) δ ppm 2.58 (m, 2 H), 3.47 (t, 7=5.6 Hz. 2 H), 4.05 (q, 7=2.8 Hz, 2 H), 6.92 (m, 1 H), 7.01 (dd, 7=7.8,4.7 Hz, 1 H), 7.84 (dd, 7=7.8, 1.7 Hz, 1 H): 7.88 (d, 7=8.8 Hz, 1 H), 8.23 (dd, 7=4.7,1.7 Hz, 1 H), 8.40 (dd, 7=8.3,2.2 Hz, 1 H),9.0l (d, 7=2.4 Hz, 1 H), 10.32 (s, 1 H). 20 Example 89 3,-Chloro-3,6-dihydro-2H-[l,2]bipyridinyl-4-carboxylicacid(4-tert-butyl-2-fluoro-pbenyl)- amide The title compound was prepared using the procedure described in Example 49D 25 using 4-tert-butyl-2-ftuoro-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 388 (M+H)+, m/z 386 (M-H)"; IH NMR (500 MHz, DMSO-D6) δ ppm 1.28 (s, 9 H), 2.55 (m, 2 H), 3.46 (t, 7=5.5 Hz, 2 H), 4.02 (q, 7=3.1 Hz, 2 H), 6.84 (m, 1 H), 7.01 (dd, 7=7.8,4!7 Hz, 1 H), 7.19 (dd, 7=8.4,2.0 Hz, 1 H), 7.24 (dd, 7=12.8,2.1 Hz, 1 H), 7.42 (t, 7=8.4 Hz, 1 H), 7.84 (dd, 7=7.6,1.5 Hz, 1 H), 8.22 (dd, 7=4.6,1.5 Hz, 1 H), 9.47 (s, 1 H). Example 90 65 WO 2005/007642 PCT/US2004/021836 3'-Chloro-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylic acid(6-chloro-pyridin-3-yl)-amide The title compound was prepared using the procedure described in Example 49D using 6-chloro-pyridin-3-ylamine instead of 4-ter-butylaniline. MS (ESI+) in/z 348 (M+H)+, 7?i/z 346 (M-H)'; IH NMR (300 MHz, DMSO-D6) δ ppm 2.55 (m, 2 H), 3.46 (t, >5.6 Hz, 2 H), 4.03 (q, .7=2.7 Hz, 2 H), 6.86 (m, 1 H), 7.01 (dd, >7.8,4.7 Hz, 1 H), 7.48 (d, >8.5 Hz, 1 H), 7.83 (dd, J=7.8,1.4 Hz, 1 H), 8.17 (dd, J=U, 2.9 Hz, 1 H), 8.23 (dd, 7=4.7,1.7 Hz, 1 H), 8.71 (d, 7=2.4 Hz, 1 H), 10.09 (s, 1 H). 10 Example 91 3,-Chloro-3,6-dihydro-2H-[l,2]bipyridinyl-4-carboxylicacid(4-tert-butyl-3-fluoro-phenyl)- amide The title compound was prepared using the procedure described in Example 49D using 4-tert-butyl-3-fluoro-aniline instead of 4-ter-butylaniline. MS (ESR) JJT/Z 388 (M+H)+, 15 m/z 386 (M-H)-; IH NMR (300 MHz, DMSO-D6) δ ppm 1.32 (s, 9 H), 2.56 (m, 2 H), 3.45 (t, 7=5.6 Hz, 2 H), 4.02 (q, 7=2.7 Hz, 2 H), 6.80 (m, 1 H), 7.00 (dd, 7=7.8,4.7 Hz, 1 H), 7.25 (t, 7=9.5 Hz, 1 H), 7.39 (dd, 7=8.8,2.4 Hz, 1 H), 7.58 (dd, 7=15.4,2.2 Hz, 1 H), 7.83 (dd, 7=7.6, 1.5 Hz, I H), 8.22 (dd, 7=4.7,1.4 Hz, 1 H), 9.85 (s, 1 H). 20 Example 92 3'-Trifluoromethyl-3r6-dihydro-2.H-[1.2']bipyridinyl-4-carboxylicacid[4-(8-aza- bicyclo[3.2.1]oct-8-yl)-phenyl]-amide Example 92A 25 8-Aza-bicyclol[3.2.1]octane To a solution of 8-Methyl-8-aza-bicyclo[3.2.1]octane (19.5 g, 0.156 mol) in DCE (500 mL) at 0 °C was added 1-chloroethyl chloroformate (19.5 mL, 0.179 mol) over 5 min. The mixture was heated to relux for 4 h, concentrated, and filtered through silica (50% Ei20/Hex). The residue was then refluxed in MeOH (150 mL) for 45 min and concentrated 30 under reduced pressure to provide 8-Aza-bicycIo[3.2.1]octane as a light yellow solid (19.2 g, 0.130 mol, 83%)%): 66 WO 2005/007642 PCTAJS2004/02J836 !H NMR (300 MHz, CDC13) 5 9.47 (brs, 2H), 4.03 (m5 2H), 2.18-2.33 (m, 4H), 1.81-1.89 (m, 2H), 1.55-1.77 (m,4H). Example 92B 5 4-f(8-Aza-bicyclo[3.2.1]oct-8-yl)-phenylamine A mixture of 4-fluoro-rritrobenzene (0.72 mL, 6.8 mmol), 8-Aza-bicyclo[3.2.1]octane .(1.01 g, 6.82 mmol), and K2C03 (1.87 g, 13.5 g) in DMSO (7 mL) was heated to 110 °C and stirred for 3 hour. The mixture was diluted with Et20 (60 mL) and washed with water (40 mL) and brine (30 mL). The organic layer was dried (Na2S04), concentrated, and triturated 10 with hexane to provide 1.27 g of a yellow solid. A mixture of the solid, HCO2NH4 (1.45 g, 23.0 mmol), and 10% Pd/C (cat) in MeOH (20 mL) was stirred overnight, filtered, and concentrated. The residue was diluted with sat. aq. NaHC03 (20 mL) and extracted with CH2CI2 (3x10 mL). The organic layer was dried (Na2S04) and concentrated under reduced pressure to provide 4-(8-Aza-bicyclo[3.2.1]oct-8-yl)-phenylamine as a dark solid. 15 'H NMR (300 MHz, CDCI3) δ 6.66 (s, 4H), 4.07 (brs, 2H), 3.14 (brs, 2H), 1.74-2.09 (m, 7H), 1.44 (m, 1H), 1.22(m,2H). Example 92C 20 3,-Trifluoromethyl-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylicacid[4-(8-aza- bicyclo[3.2.1 loct-8-yI)-phenyl]-amide The title compound was prepared using the procedure described in Example 49D using 4-(8-Aza-bicyclo[3.2.1]oct-8-yI)-phenylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 457 (M+H)+; 1H NMR (400 MHz, Methawl-D4) δ ppm 1.29 (m, 2 H), 1.44 (m, 1 H), 25 1.88 (m, 5 H), 2.06 (m, 2 H), 2.61 (m, 2 H), 3.46 (t, J=S.5 Hz, 2 H), 4.01 (q, >2.9 Hz, 2 H), 4.17 (s, 2 H), 6.72 (m, 1 H), 6.80 (d, >8.9 Hz, 2 H), 7.11 (dd, J=7.8,4.8 Hz, 1 H), 7.39 (d, .7=8.9 Hz, 2 H), 8.00 (dd, >7.8,1.7 Hz, 1 H), 8.45 (d, .7=4.9 Hz, 1 H). 30 Example 93 3'-Trifluoromethyl-3,6-dihydro-2H-[1,2']bipyridinyl-4-carboxylicacid [4-(8-aza-bicyclo|3.2.1]oct-8-yl)-3-fluoro-phenyl]arnide 67 WO 2005/007642 PCT/US2004/02I836 The title compound was prepared using the procedure described in Example 49D using 4-(8-aza-bicyclo[3.2.1]oct-8-yl)-3-fluoro-phenyIamine instead of 4-ter-butylaniline. MS (ESI+) m/z 475 (M+H)*, m/z 473 (M-H)'; IH NMR (400 MHz, Metiumol-D4) δ ppm 1.44 (nC3 H), 1.87 (m, 7 H), 2.60 (m, 2 H), 3.45 (t, 7=5.5 Hz, 2 H), 4.00 (q,7=3.0 Hz, 2 H), 5 4.13 (s, 2 H), 6.72 (m, 1 H), 6.89 (t, 7=9.8 Hz, 1 H), 7.10 (dd, 7=7.8,4.8 Hz, 1 H), 7.20 (dd, 7=8.7,2.3 Hz, 1 H), 7.42 (dd, 7=15.6,2.5 Hz, 1 H), 7.99 (dd, 7=7.8,1.7 Hz, 1 H), 8.44 (dd, 7=4.6,1.2 Hz, IH). 10 Example 94 3'-Trifluoromethyl-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylicacid |4-(8-aza-bicyclo[3.2.11oct-8-yl)-3,5-difluoro-phenyflamide The title compound was prepared using the procedure described in Example 49D using 4-(8-aza-bicyclo[3.2.1]oct-8-yl)-3,5-difluoro-phenylarnine instead of 4-ter-butylaniline. 15 MS (ESI+) m/z 493 (M+H)+, m/z 491 (M-H)'; IH NMR (400 MHz, Methanol-D4) δ ppm 1.50 (m: 3 H), 1.86 (m, 7 H), 2.59 (m, 2 H), 3.44 (t,7=5.5 Hz, 2 H), 4.00 (q,7=3.1 Hz, 2 H), 4.03 (s, 2 H), 6.71 (m, 1 H), 7.10 (dd, 7-7.8,4.8 Hz, 1 H), 7.21 (d, 7=12.9 Hz, 2 H), 7.99 (dd, 7=7.8, 1.7 Hz, I H), 8.44 (dd,7=4.6, 1.2 Hz, 1 H). 20 Example 95 3 '-Trifluoromethyl-3,6-dihydro-2H-[1 ,2]bipyridinyl-4-carboxylic acid (4-chloro-3-fluoro- phenyl)-amide The title compound was prepared using the procedure described in Example 49D 25 using 3-fluoro-4-chloro-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 400 (M+H)+> m/z 398 (M-H)'; IH NMR (400 MHz, CHLOROFORM-D) δ ppm 2.64 (m, 2 H), 3.50 (t, . 7=5.5 Hz, 2 H), 4.05 (q, 7=3.1 Hz, 2 H), 6.77 (m, 1 H), 6.99 (dd, 7=7.8,4.8 Hz, 1 H), 7.16 (m, 1 H),7.31 (t, 7=8.9 Hz, 1 H),7.58(s, 1 H), 7.66 (dd, 7=11.0,2.5 Hz, 1 H),7.88(dd, 7=7.7, 1.8 Hz, 1 H), 8.42 (dd, 7=4.6,1.5 Hz, 1 H). Example 96 68 WO 2005/007642 PCT/US2004/021836 3,-TrifluoTomethyl-3,6-dihydro-2H"-[1,2']bipyridinyl-4-carboxylicacid(4-tert-butyl-3- fluoro-phenyl)-amide The title compound was prepared using the procedure described in Example 49D using 3-fluoro-4-tert-butyl-aniline instead of 4-ter-butylaniline. MS (ESR) m/z 422 (M+H)+, 5 m/z 420 (M-H)-; IH NMR (400 MHz, CHLOROFORIid-D) δ ppm 1.36 (s, 9 H), 2.65 (m, 2 H), 3.51 (t, 7=5.5 Hz, 2 H), 4.05 (q, 7=3.1 Hz, 2 H), 6.76 (m, 1 H), 6.98 (dd, 7=7.4, 5.2 Hz, 1 H), 7.11 (m, 1 H), 7.23 (t, 7=8.7 Hz, 1 H), 7.44 (m, 2 H), 7.88 (dd, 7=8.0,1.8 Hz, 1 H), 8.42 (dd, 7=4.6,1.2Hz, IH). 10 Example 97 3'-Trifluorornethyl-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylic acid ["4-( 1-hydroxy-1- methyl-ethyl)-phenyl]-amide 15 The title compound was prepared using the procedure described in Example 49D using 4-(l-hydroxy-l-methyl-ethyl)-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 406 (M+H)+ (80%), m/z 38S (M-17)+ (100%), m/z404 (M-H)"; 1HNMR (400 MHz, CHLOROFORM-D) δ ppm 1.57 (s, 6 H), 2.65 (m, 2 H), 3.49 (t, 7=5.4 Hz, 2 H), 4.03 (q, .7=3.0 Hz, 2 H), 5.29 (s, 1 H), 6.75 (m, 1 H), 6.98 (dd,7=7.4,4.3 Hz, 1 H), 7.44 (m, 2 H), 20 7.51 (m, 2 H), 7.54 (s, I H), 7.88 (dd, 7=7.8, 1.7 Hz, 1 H), 8.41 (dd, 7=4.8,1.4 Hz, 1 H). Example 98 2-Methyl-2-{4-[(33-trifluoromethyl-3,6-dihydro-2H-[l,2]bipyridinyl-4-carbonyn-amino1- 25 phenyl}-propionic acid methyl ester The title compound was prepared using the procedure described in Example 49D using 2-(4-Amino-phenyl)-2-methyl-propionic acid methyl ester instead of 4-ter-butylaniline. MS (ESI+) m/z 448 (M+H)+, m/z 446 (M-H)"; IH NMR (400 MHz, CHLOROFORM-D) δ ppm 1.57 (s, 6 H), 2.65 (m, 2 H), 3.50 (t, 7=5.4 Hz, 2 H), 3.64 (s, 3 H), 4.04 (q, 7=3.1 Hz, 2 30 H), 6.75 (m, 1 H), 6.98 (dd, 7=7.4, 5.2 Hz, 1 H), 7.30 (m, 2 H), 7.51 (m, 3 H), 7.88 (dd, 7=7.7, 1.8 Hz, 1 H), S.41 (dd, 7=4.9,1.2 Hz, 1 H). 69 WO 2005/007642 PCT/US2004/02J836 Example 99 l'Pyrimidin-2-yl-l,23,64etrahydro-pyridine-4-carboxylicacidr4-(8-aza-bicyclor3.2.11oct-8- yl)-fluoro-phenyl]-amide 5 The title compound was prepared using the procedure described in Example 52B using 4~(8-aza-bicycIo[3.2.1]oct-8-yl)-3-fluoro-phenylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 408 (M+H)+, m/z 406 (M-H)'; 1H NMR (400 MHz, DMSO-D6) δ ppm 1.42 (m, 3 H), 1.76 (m, 5 H), 1.94 (m, 2 H), 2.44 (m, 2 H), 3.91 (t, 7=5.7 Hz, 2 H), 4.14 (s, 2 H), 4.35 (qs .7=2.8 Hz, 2 H), 6.67 (t, 7=4.8 Hz, 1 H), 6.74 (m, 1 H), 6.97 (t, 7=9.5 Hz, 1 H), 7.31 10 (dd, 7=8.6,2.1 Hz, 1 H), 7.57 (dd, 7=16.0,2.5 Hz, 1 H), 8.41 (d, 7=4.6 Hz, 2 H), 9.69 (s, 1 H). Example 100 15 l-Pyrimidin-2-yl-l,2.3,6-tetrahydro-pyridine-4-carboxylicacid [4-(8-aza-bicyclo|"3.2.11oct-8- yl)-3,5-difluoro-phenyl1-amide The title compound was prepared using the procedure described in Example 52B using 4-(8-aza-bicyclo[3.2.1]oct-8-yl)-3,5-difluoro-phenylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 426 (M+H)+, m/z 424 (M-H)'; 1H NMR (400 MHz, DMSO-D6) 5 ppm 1.46 20 (m, 3 H), 1.74 (m, 5 H), 1.91 (m, 2 H), 2.44 (m, 2 H), 3.91 (t, 7=5.7 Hz, 2 H), 3.97 (m, 2 H), 4.35 (q, 7=2.8 Hz, 2 H), 6.67 (t, 7=4.8 Hz, 1 H), 6.76 (m, 1 H), 7.35 (d, 7=13.5 Hz, 2 H), 8.40 (d, 7=4.9 Hz, 2 H), 9.78 (s, 1 H). 25 Example 101 l-Pyrimidin-2-yl-l,23.6-tetrahydro-pyridine-4-carboxylic acid(4-azepan-1-yl-phenyl)-amide The title compound was prepared using the procedure described in Example 52B using 4-azapan-l-yl-phenylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 378 (M+H)+, m/z 376 (M-H)-; 1H NMR (400 MHz, DMO-D6) δ ppm 1.50 (s, 4 H), 1.75 (s, 4 H), 2.45 (m, 30 2 H), 3.45 (m, 4 H), 3.91 (t, 7=5.7 Hz, 2 H), 4.33 (q, J=2.8 Hz, 2 H), 6.67 (t, 7=4.6 Hz, 1 H), 6.73 (m, 3 H), 7.46 (d, 7=8.9 Hz, 2 H), 8.40 (d, 7=4.6 Hz, 2 H), 9.46 (s, 1 H). 70 WO 2005/007642 PCT/US2004/021836 Example 102 3'-Chloro-3,6-dihyto-2H-[l,2]bipyridinyl-4—carboxylic acid(2,2,3,3-tetrafluoro-2,3- dihydro-ben2Qfl,4]dioxin-6-yl)-amide 5 The title compound was prepared using the procedure described in Example 49D using 2,2,3,3-tetrafluoro-2,3-dihydro-benzo[l,4]dioxin-6-ylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 444 (M+H)+ (40%), m/z 330 (M-l 13)+ (100%), m/z 442 (M-H)'; 1H NMR (400 MHz, DMSO-D6) δ ppm 2.56 (m, 2 H), 3.46 (t, 7-5.5 Hz, 2 H), 4.03 (q, 7=2.9 Hz, 2 H), 6.82 (m, 1 H), 7.00 (dd, 7=7.7,4.6 Hz, 1 H), 7.43 (m, 1 H), 7.57 (dd, 7=9.2,2.5 Hz, 10 1 H), 7.82 (dd, 7=7.7,1.5 Hz, 1 H), 7.87 (d, 7=2.5 Hz, 1 H), 8.22 (dd, 7=4.8,1.7 Hz, 1 H), 10.03 (s, 1 H). Example 103 15 1 -Pyrimidin-2-yl-l ,2,3.6-tetrahydro-pyridine-4-carboxylic acid (4-tert-butyl-3-fluoro- phenyl)-amide The title compound was prepared using the procedure described in Example 52B using 4-tert-butyl-3-fluoro-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 355 (M+H) (90%), m/z 114 (M-240)4" (100%), m/z 353 (M-H)"; 1H NMR (300 MHz, DMSO-D6) δ ppm 20 1.32 (s, 9 H), 2.45 (m, 2 H), 3.91 (t, 7=5.6 Hz, 2 H), 4.36 (q, 7=2.4 Hz, 2 H), 6.67 (t, 7=4.7 Hz, 1 H), 6.78 (m, 1 H), 7.25 (m, 2 H), 7.38 (dd, 7=8.5,2.0 Hz, 1 H), 7.57 (dd, 7=15.3,2.0 Hz, 1 H), 8.40 (d, 7=4.7 Hz, 1 H), 9.85 (s, 1 H). 25 Example 104 3'-Trifluoromethyl-3.6-dihydro-2if-|"l,2,1bipyridinyl-4-carboxylicacid [4-(2-hydroxy-l,1- dimethyl-ethyl)-phenyl]amide The title compound was prepared using the procedure described in Example 49D using 4-(2-hydroxy-1.1 -dimethyl-ethyl)-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 30 420 (M+H)+, m/z 418 (M-H)"; 1H NMR (300 MHz, CHLOROFORM-D) 5 ppm 1.33 (s, 6 H), 2.04 (s, 1 H), 2.67 (m. 2 H), 3.53 (t, 7=5.4 Hz, 2 H), 3.60 (s, 2 H), 4.07 (q, 7=2.8 Hz, 2 H), 71 WO 2005/007642 PCT/US2004/021836 6.77 (m, 1 H), 6.99 (dd, 7=7.8, 4.7 Hz, 1 H), 7.36 (d, 7=8.5 Hz, 2 H), 7.41 (s, 1 H), 7.53 (d, 7=8.8 Hz, 2 H), 7.89 (dd, 7=7.8,1-7 Hz, 1 H), 8.43 (d, .7=4.7 Hz, 1 H). 5 Example 105 1 -Pyrimidin-2-yl-l ,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-trifluoromethyl-phenyl)- amide The title compound was prepared using the procedure described in Example 52B using 4-trifluoromethyl-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 348 (M+H)+ 10 (40%), m/z 367 (M+19)+ (100%), m/z 346 (M-H)"; IH NMR (300 MHz, DMSO-D6) δ ppm 2.48 (m, 2 H), 3.93 ft .7=5.8 Hz, 2 H), 4.38 (q, 7=2.7 Hz, 2 H), 6.67 ft 7=4.7 Hz, 1 H), 6.84 (m, 1 H), 7.68 (d, .7=8.8 Hz, 2 H), 7.91 (d, 7=8.5 Hz, 2 H), 8.41 (d, 7=4.7 Hz, 2 H), 10.10 (s, 1 H). Example 106 l-Pyriniidin-2-yl-l,2.3.6-tetrahydro-pyridine-4-carboxylicacid(4-chloro-3-fluoro-phenyl)- amide The title compound was prepared using the procedure described in Example 52B 20 using 4-chloro-3-fluoro-aniline instead of 4-ter-butylaniline. MS (DCI+) m/z 333 (M+H)+; IH NMR (300 MHz, DMSO-D6) δppm 2.47 (m, 2 H), 3.92 (t, 7=5.6 Hz, 2 H), 4.37 (q, 7=2.9 Hz, 2 H), 6.67 ft 7=4.7 Hz, 1 H), 6.81 (m, 1 H), 7.52 (m, 2 H), 7.85 (m, 1 H), 8.40 (d, 7=4.7 Hz, 2 H), 10.05 (s J H). 25 Example 107 2-Methyl-2-{4-rn-pyrimidin-2-yl-l,2,3,6-tetrahydro-pyridine-4-carbonyn-amino1-phenyl)- propionic acid methyl ester The title compound was prepared using the procedure described in Example 52B 30 using 4- propionic acid methyl ester-aniline instead of 4-ter-butylaniline. MS (DCI+) m/z 381 (M+H)+; IH NMR (300 MHz, DMSO-D6) δ ppm 1.48 (s, 6 H), 2.45 (m, 2 H), 3.58 (s, 3 72 WO 2005/007642 PCT/US2004/021836 H), 3.91 (t, 7-5.6 Hz, 2 H), 4.35 (q, 7=2.9 Hz, 2 H), 6.67 (t, 7=4.7 Hz, 1 H), 6.77 (m, 1 H), 7.24 (d, 7-8.8 Hz, 2 H), 7.62 (d, 7=8.8 Hz, 2 H), 8.40 (d, 7=4.7 Hz, 2 H), 9.73 (s, 1 H). 5 Example 108 3'-Chloro-3,6-dihydro-2H-ri,2']bipyridinyl-4-carboxylic acid K-(ethyl-isopropyl-amino)- phenyl]-amide hydrochloride The title compound was prepared using the procedure described in Example 49D using 4-(ethyl-isopropyl-amino)-phenylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 10 399 (M+H)+, m/z 397 (M-H)"; IH NMR (300 MHz, DMSO-D6) δ ppm 0.99 (t, 7=7.1 Hz, 3 H), 1.11 (d, 7=6.1 Hz, 3 H), 1.35 (d, 7=5.8 Hz, 3 H), 2.57 (s, 2 H), 3.61 (m, 2 H), 3.86 (s, 1 H), 4.03 (q, 7=2.7 Hz, 2 H), 6.84 (m, 1 H), 7.01 (dd, 7=7.8,4.7 Hz, 1 H), 7.66 (d, 7=8.8 Hz, 2 H), 7.84 (dd, 7=7.8,1.7 Hz, 1 H), 7.90 (d, 7=8.8 Hz, 2 H), 8.23 (dd, 7=4.7,1.4 Hz, 1 H), 10.07 (s, IH), 11.94 (s, IH). 15 Example 109 3’-Trifluoromethyl-3,6-dLhydro-2H-[1,2]bipyridinyl-4-carboxylic acid (4-trifluoromethyl- phenyl)-amide 20 The title compound was prepared using the procedure described in Example 49D using 4-trifluoromethyl-aniline instead of 4-ter-butylaniline. MS (ESI+) m/z 416 (M+H)+, m/z 414 "(M-H)"; IH NMR (300 MHz, CHLOROFORM-D) δ ppm 2.68 (m, 2 H), 3.52 (t, 7=5.6 Hz, 2 H), 4.08 (q, 7=3.1 Hz, 2 H), 6.81 (m, 1 H), 7.00 (dd, 7=7.8, 4.7 Hz, 1 H), 7.54 (s, 1 H), 7.60 (d, 7=8.5 Hz, 2 H), 7.70 (d, 7=8.5 Hz, 2 H), 7.89 (dd, 7=7.8,1.7 Hz, 1 H), 8.43 (dd, 25 7=4.7, 1.4 Hz, 1 H). Example 110 3'-Trifluoromethyl-3,6-dmydro-2J?-[l,2]bipyridinyl-4-carboxylicacid (4-acetyl-phenyl)- 30 amide The title compound was prepared using the procedure described in Example 49D using 4-acetyl-phenylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 390 (M+H)+, m/z 73 WO 2005/007642 PCT/US2004/021836 388 (M-H)"; 1HNMR (300 MHz, CHLOROFORhd-D) δ ppm 2.59 (s, 3 H), 2.68 (m, 2 H), 3.52 (t, 7=5.4 Hz, 2 H), 4.08 (q, 7=3.1 Hz, 2 H), 6.81 (m, 1 H), 7.00 (dd, 7=7.1,4.7 Hz, 1 H), 7.59 (s, 1 H), 7.68 (d, 7=8.8 Hz, 2 H), 7.90 (dd, 7=7.8,1.7 Hz, 1 H), 7.97 (d, 7=8.5 Hz, 2 H), 8.43 (dd, 7=4.7,1.4 Hz, 1 H). 5 Example 111 4-f(3'-Trifluoromemyl-3,6-dihydro-2H-[1,2]bipyridiny-4-carbonyl)-amino]-benzoic acid methyl ester 10 The title compound was prepared using the procedure described in Example 49D using 4-benzolic acid methyl ester-phenylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 406 (M+H)+, m/z 404 (M-H)"; 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 2.68 (m, 2 H), 3.52 (t, 7=5.4 Hz, 2 H), 3.90 (s, 3 H), 4.08 (q, 7=3.1 Hz, 2 H), 6.80 (m, 1 H), 7.00 (dd, 7=7.8, 5.8 Hz, 1 H), 7.56 (s, 1 H), 7.66 (dt, 7=9.0,2.4,2.2 Hz, 2 H), 7.89 (dd,7=7.8,1.7 Hz, 1 15 H), 8.03 (dt, 7=9.0,2.4,2.2 Hz, 2 H), 8.43 (dd, 7=4.7,1.4 Hz, 1 H). Example 112 3'-Chloro-3,6-dihydro-2H-[1,2]bipyridinyl-4-Carboxylic acid (3,4,5,6-tetrahydro-2H- 20 [l,2]bipyridinyl-5-yl)-amide The title compound was prepared using the procedure described in Example 49D using 3,4,5,6-tetrahydro-2H-[l;2']bipyridinyl-5,-ylamine instead of 4-ter-butylaniline. MS (ESI+) m/z 398 (M+H)+. m/z 396 (M-H)' (30%), m/z 213 (M-186)- (100%); 1H NMR (300 MHz, DMSO-D&) δ Ppm 1.65 (s, 6 H), 2.55 (m, 2 H), 3.46 (t, J=5A Hz, 2 H), 3.65 (s, 4 H), 25 4.04 (q, 7=2.7 Hz, 2 H), 6.89 (m, 1 H), 7.01 (dd, 7=7.6,4.6 Hz, 1 H), 7.45 (d, 7=9.8 Hz, 1 H), 7.83 (dd, 7=7.6,1.5 Hz, 1 H), 8.18 (dd, 7=10.0,2.5 Hz, 1 H), 8.22 (dd, 7=4.7,1.7 Hz, 1 H), 8.51 (d, 7=2.4 Hz, 1 H); 10.08 (s, 1 H). 30 Example 113 3'-Chloro-3,6-dihydro-2H"-[l.2']bipyridinyl"4-carboxylicacid(6-azepan-l-yl-pyridin-3-yl)- amide 74 VO 2005/007642 PCT/US2004/021836 The title compound was prepared using the procedure described in Example 49D using 6-azepan-l-yl-pyridin-3-ylarnine instead of 4-ter-butylaniline. MS (ESI+) m/z 412 (M+H)+>™/z410(M-Hy; 1H NMR (300 MHz, DMSO-D6) δ ppm 1.52 (m,4H), 1.77 (s, 4 H), 2.55 (m, 2 H), 3.46 (t, 7=5.4 Hz, 2 H), 3.69 (m, 4 H), 4.03 (q, 7=2.7 Hz, 2 H), 6.89 (m, 1 5 H), 7.01 (dd, 7=7.8, 4.7 Hz, 1 H), 7.35 (d, 7=9.5 Hz, 1 H), 7.83 (dd, 7=7.8,1.7 Hz, 1 H), 8.18 (dd, 7=10.0, 2.5 Hz, 1 H), 8.22 (dd, 7=4.7,1.7 Hz, 1 H), 8.51 (d, 7=2.4 Hz, 1 H), 10.08 (s, f H). 10 Example 114 3'-Chloro-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylic acid (4-cyclopropyl-phenyl)-amide The title compound was prepared using the procedure described in Example 49D using 4-cyclopropane-aniline instead of 4-tert-butylaniline. MS (ESI+) m/z 354 (M+H)4", m/z 352 (M-HV; 1H NMR (300 MHz, DMSO-D6) δ ppm 0.61 (m, 2 H), 0.90 (m, 2 H), 1.86 (m, 1 15 H), 2.55 (m, 2 H), 3.45 (t, 7=5.4 Hz, 2 H), 4.00 (q, .7=2.5 Hz, 2 H), 6.76 (m, 1 H), 7.00 (m, 3 H), 7.55 (m, 2 H), 7.82 (dd, 7=7.8,1.7 Hz, 1 H), 8.22 (dd, 7=4.7,1.7 Hz, 1 H), 9.63 (s, 1 H). Example 115 20 l-Pyrimidin-2-yl-1,2.3.6.-tetrahydro-pyridine-4-carboxylic acid(6-trifluoromethyl-pyridin-3- yl)-amide The title compound was prepared using the procedure described in Example 49D using 6-trifluoromethyl-pyridin-3-ylarnine instead of 4-tert-butylaniline. MS (DCI+) m/z 350 (M+H)+; 1H NMR (300 MHz, DMSO-D6) δ ppm 2.48 (m, 2 H), 3.93 (t, 7=5.8 Hz, 2 H), 4.40 25 (q, 7=2.9 Hz, 2 H), 6.68 (t, 7=4.7 Hz, 1 H), 6.91 (m, 1 H), 7.88 (d, 7=8.5 Hz, 1 H), 8.40 (m, 3 H), 9.00 (d, 7=2.4' Hz, 1 H), 10.32 (s, 1 H). Example 116 30 1 -Pyrimidin-2-yl-1.2.3,6-tetrahydro-pyridine-4-carboxylic acid (4-acetyl-phenyl)-amide The title compound was prepared using the procedure described in Example 52B using 4-acetyl-aniline instead of 4-tert-butylaniline. MS (DC1+) m/z 323 (M+H)+; 1H NMR 75 WO 2005/007642 PCT/US200-i/021837.8,4.7 Hz, 1 H), 7.22 (m, 2 H), 7.73 (dd, >7.8,1.7 Hz, 1 H), 8.16 (dd, J=4.7J.7Hz,lH). Example 132 10 3'-Trifluoromethyl-3,6-dihydro-2H-[ 1,2]bipyridmyl-4-carboxylic acid (4-tert-butyl-2- chloro-phenyl)amide The title compound was prepared using the procedure described in Example 49D using 2-chloro-44ert-butyl-phenylarnine instead of 4-tert-butylaniline. MS (ESI+) m/z 438 (M+H)\ vi/z 436 (M-H)'; 1HNMR (300 MHz, CHLOROFORM-D) δ ppm 1.30 (s, 9 H)5 2.69 15 (m, 2 H), 3.55 (t, J=5.4 Hz, 2 H), 4.10 (q, J=3.1 Hz, 2 H), 6.86 (m, 1 H), 6.98 (dd, J=7.3, 5.3 Hz, 1 H), 7.31 (dd, >8.S, 2.4 Hz, 1 H), 7.38 (d, >2.4 Hz, 1 H), 7.89 (dd, J=7.8,1.7 Hz, 1 H), 7.97 (s, 1 H), 8.34 (d, .7=8.8 Hz, 1 H), 8.43 (dd, J=4.9, 1.5 Hz, 1 H). 20 Example 133 l-Thiazol-2-yl-l,2,3.6-tetrahydro-pyridine-4-carboxylicacid(4-trifluoromethanesulfonyl- phenyl)-amide 25 Example 133 A 1 -Thiazol-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid A mixture of 2-bromooxazole (4.98 mmol), and isoguvacine, sodium salt (1.2 g. 8.2 mmol) in water (7 mL) was heated to 90 °C and stirred for 4 hour. Additional isoguvacine, sodium salt (0.52 g, 3.3 mmol) was then added and stirred overnight. The mixture was 30 diluted with water and extracted with CH2CI2. The aqueous layer was acidified with cone HC1 (pH-3) and extracted with CHCI3. The organic layer was dried (Na2SO4) and 81 WO 2005/007642 PCT/US2004/021836 concentrated under reduced pressure to provide l-Thiazol-2-yl-l,2,3,6-tetrahydro-p)Tidine-4- carboxylic acid a solid. Example 133B 5 l-Thiazol-2-yl-l,23t6-tetrahydro-pyridine-4-carboxylicacid(4-trifluoromethanesulfonyl- Phenyl)-amide The title compound was prepared using the procedure described in Example 52D using 4-trifluoromethanesulfonyl-phenyIamine instead of 4-tert-butylaniline. MS (DCI+) m/z 418 (M+H)+ (40%), m/z 243 (M-174)+ (100%); IHNMR (300 MHz, DMSO-D6) δ ppm 2.55 10 (m, 2 H), 3.63 (t, 7=5.8 Hz, 2 H), 4.15 (q, J=2.S Hz, 2 H), 6.87 (d, 7=3.4 Hz, 2 H), 7.20 (d, 7=3.4 Hz, 1 H), 8.10 (m, 4 H), 10.52 (s, 1 H). Example 134 15 1 -Thiazol-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-terf-butyl-phenyl)-amide The title compound was prepared using the procedure described in Example 52D. MS (DCI+) m/z 342 (M+H)+; 1H NMR (300 MHz, DMSO-D6) δ ppm 1.26 (s, 9 H), 2.53 (m, 2 H), 3.62 (t, 7=5.8 Hz, 2 H), 4.10 (q,7=2.7 Hz, 2 H), 6.74 (m, 1 H), 6.86 (d, 7=3.7 Hz, 1 H), 7.20 (d, 7=3.7 Hz, 1 H), 7.32 (d, 7=8.8 Hz, 2 H), 7.58 (d, 7=8.8 Hz, 2 H), 9.71 (s, 1 H). 20 Example 135 3,-Trifluoromemyl-3,6-dmydro-2H-[l,2,lbipyridinyl-4-carboxylic acid (4- dimethylsulfamoyl-phenyl)-amide 25 The title compound was prepared using the procedure described in Example 52D using 4-dimethylsulfamoyl-phenylamine instead of 4-tert-butylaniiine. MS (ES1+) m/z 455 (M+H)+, m/z453 (M-H)-; IHNMR (300 MHz, CHLOROFORM-D) δppm 2.68 (m, 2 H), 2.71 (s, 6 H), 3.53 (t, 7=5.4 Hz, 2 H), 4.09 (q, 7=2.9 Hz, 2 H), 6.83 (m, 1 H), 7.02 (dd, 7=7.8, 4.7 Hz, 1 H), 7.65 (s, 1 H), 7.76 (s, 4 H), 7.91 (dd, 7=7.8,1.7 Hz, 1 H), 8.44 (dd, 7=4.6,1.5 30 Hz, 1 H). 82 WO 2005/007642 PCT/US2004/021836 Example 136 3,-Trifluoromethyl-3,6-dihydro-2H-[l,2'1bipyridinyl-4-carboxylicacid[4-(piperidine-l- sulfonyl)-phenyl]-amide The title compound was prepared using the procedure described in Example 52D 5 using 4-(piperidine-l-sulfonyl 4-(piperidine-"r-sulfonyl -phenylamine instead of 4-tert-butylaniline. MS (ESI+) m/z 495 (M+H)+, m/z 493 (M-H)'; 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.44 (m, 2 H), 1.64 (m, 4 H), 2.68 (m, 2 H), 2.98 (t, 7=5.4 Hz, 4 H),'3.54 (t, 7=5.6 Hz, 2 H), 4.10 (q, 7=2.8 Hz, 2 H), 6.82 (m, 1 H), 7.02 (dd, 7=7.5,4.4 Hz, 1 H), 7.67 (m, 1 H), 7.74 (s, 4 H), 7.92 (dd, 7=7.8,1.7 Hz, 1 H), 8.44 (dd, 7=5.1,1.4 Hz, 1 H). 10 Example 137 3,-Trifluorornethyl-3,6-dihydro-2-H-[l,2']bipyridinyl-4-carboxylicacid(5-iodo-pyridin-2-yl)- amide 15 The title compound was prepared using the procedure described in Example 52D using 5-iodo-pyridin-2-ylamine instead of 4-tert-butylaniIine. MS (ESI+) m/z 475 (M+H)+, m/z 473 (M-H)-; 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 2.67 (m, 2 H), 3.51 (t, 7=5.4 Hz, 2 H), 4.07 (q,7=3.1 Hz, 2 H), 6.86 (m, 1 H), 6.99 (dd, 7=7.8,4.7 Hz, 1 H), 7.89 (dd, 7=7.8,2.0 Hz, 1 H), 7.98 (dd, 7=8.8,2.4 Hz, 1 H), 8.15 (m, 2 H), 8.42 (dd, 7=4.7,1.4 Hz, 20 1 H), 8.47 (d, 7=1.7 Hz, 1 H). Example 138 3,-Trifluoromethyl-3,6-dihydro-2H-[1,2']bipyridinyl-4-carboxylicacid(3,4-difluoro- 25 phenyl)-amide The title compound was prepared using the procedure described in Example 52D using 3,4-difluoro-phenylamine instead of 4-tert-butylaniline. MS (ESI+) m/z 384 (M+H)+, m/z 382 (M-H)"; 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 2.65 (m, 2 H), 3.52 (t, 7=5.6 Hz, 2 H), 4.07 (q, 7-3.1 Hz, 2 H), 6.78 (m, 1 H), 7.00 (dd, 7=7.8,4.7 Hz, 1 H), 7.12 30 (m, 2 H), 7.41 (s, 1 H), 7.68 (m, 1 H), 7.90 (dd, 7=7.8,1.7 Hz, 1 H), 8.43 (dd, 7=4.7,1.4 Hz, 1H) 83 WO 2005/007642 PCT/US2004/021836 Example 139 3 '-Chloro-3 .6-dihydro-2H-[1, 2]bipyridinyl-4-carboxylic acid (4-methanesulfonyl-phenyl)- amide 5 The title compound was prepared using the procedure described in Example 49D using 4-methanesulfonyl-phenylamine instead of 4-tert-butylaniIine. MS (DCI+) m/z 392 (M+H)+ (20%), m/z 206 (M-l 85)+ (100%); 1H NMR (300 MHz, DMS0-D6) δ ppm 2.57 (m, 2 H), 3.17 (s, 3 H), 3.46 ft J=5A Hz, 2 H), 4.04 (q, >2.8 Hz, 2 H), 6.87 (m, 1 H), 7.01 (dd, J=7.8,4.7 Hz, 1 H), 7.85 (m, 4 H), 7.96 (dt, J^9.0,2.4,2.2 Hz, 2 H), 8.23 (dd, J*=4.6,1.5 Hz, 10 1H). Example 140 3 ‘-DimethylsuIfamoyl-3,6-dihydro-2H-[1,2']bipyridinyl-4-carboxyIic acid (4-ferf-butyI- 15 phenyl)-amide Example 140A 2-Chloro-pyridine-3-sulfonic acid dimethylamide 20 A solution of Me2NH in THF (2M, 8 mL, 16 mmol) was added to 3-(2- chloropyridyl)suIfonyl chloride (J. Med. Chem. 1980,23,1376) (2.1 g, 9.9 mmol) in THF (10 mL), and stirred 10 hours, quenched with sat aq NH4CI, extracted with EtOAc, and purified by flash chromatography (30% EtOAc/Hex) to provide sulfonamide as a red oil 25 Example 140B l-Thiazol-2-yl-l,2,3,6-tetrahydro-pyridine-4-carboxylicacid A solution of 2-chIoro-pyridine-3-sulfonic acid dimethylamide (1.18 mmol) and isoguvacine, sodium salt (2.19 mmol) in THF (0.5 mL) and water (2 mL) was stirred at 90 °C for 22 hours, acidified (pH~l) with TFA, and extracted with CH2CI2. The organic layer was 30 dried (Na2S04), concentrated, and purified by flash chromatography (5% MeOH/CH2Cl2) and trituration (Et20) to provide as a white solid. *H NMR (300 MHz, CD3OD) δ 8.47 (dd, 84 WO 2005/007642 PCT/US2004/021836 J=1.7,4.8 Hz, IH), 8.22 (dd, J=1.7,7.8 Hz, IH), 7.22 (dd, J-4.8,7.8 Hz, IH), 7.03 (sept, J=1.7 Hzs IH), 3.99 (q, J=3.0 Hz, 2H), 3.40 (t, J=5.6 Hz, 2H), 2.73 (s, 6H), 2.56 (m, 2H). 5 Example 140C 3'-Dimethylsulfamoyl-3,6-dihydro-2.H-[l,2']bipyridinyl-4-carboxyIicacid('4-tert-butyl- phenyl)-amide The title compound was prepared using the procedure described in Example 52D using 4-tert-butylaniline. MS (ESI+) m/z 443 (M+H)+, m/z 441 (M-H)'; IH NMR (300 MHz, 10 CHLOROFOUd-D) δ ppm 1.31 (s, 9 H), 2.73 (s, 2 H), 2.77 (s, 6 H), 3.56 (t, 7=5.6 Hz, 2 H), 4.08 (q, .7=2.9 Hz, 2 H), 6.84 (m, 1 H), 7.10 (dd, 7=7.8,4.7 Hz, 1 H), 7.36 (m, 2 H), 7.39 (d, 7=2.0 Hz, 1 H), 7.49 (m, 2 H), 8.18 (dd, 7=8.0,1.9 Hz, 1 H), 8.45 (dd, .7=4.7,2.0 Hz, 1 H). 15 Example 141 3’-Dimethylsulfamoyl-3,6-dihydro-2H-[l ,2]bipyridinyl-4-carboxylic acid (4-chloro-phenyI)- amide The title compound was prepared using the procedure described in Example 52D using 4-chloro-phenylarnine instead of 4-tert-butylaniline. MS (ESI+) m/z 421 (M+H)+, t)i/z 20 419 (M-H)"; IH NMR (300 MHz, CHLOROFORM-D)δppm 2.72 (s, 2 H), 2.77 (s, 6 H), 3.56 (t,7=5.4 Hz, 2 H), 4.08 (d, 7=2.4 Hz, 2 H), 6.86 (s, 1 H), 7.10 (dd, 7=8.0,4.6 Hz, 1 H), 7.31 (ds 7=8.8 Hz, 2 H), 7.43 (s, 1 H), 7.54 (d, 7=9.2 Hz, 2 H), 8.17 (dd, 7=7.8,1.4 Hz, 1 H), 8.45 (dd, 7=4.6,1.5 Hz, 1 H). 25 Example 142 3'-Dimethylsulfamoyl-3,6-dihydro-2H[1,2,]bipyridinyl-4-carboxylicacid(4- trifluoromethoxy-phenyl)-amide The title compound was prepared using the procedure described in Example 52D 30 using 4-trifluoromethoxy-phenylamine instead of 4-tert-butylaniline. MS (ESI+) m/z 471 (M+H)\ m/z 469 (M-H)-; IH NMR (300 MHz, CHLOROFOMd-D) δ ppm 2.72 (s, 2 H), 2.77 (s, 6 H), 3.57 (t, 7=5.3 Hz, 2 H), 4.09 (s, 2 H), 6.87 (s, I H), 7.11 (dd, 7=7.8,4.4 Hz, 1 H), 85 WO 2005/007642 PCT/US2004/02183(1 7.20 (d, .7=8.1 Hz, 2 H), 7.48 (s, 1 H), 7.62 (d, ,7=8.8 Hz, 2 H), 8.18 (d, >7.5 Hz, 1 H), 8.46 (d,J=3.7Hz,lH). (5) Biological Data 5 (a) In Vitro Data - Determination of Inhibition Potencies Dulbecco's modified Eagle medium (D-MEM) (with 4.5 mg/mL glucose) and fetal bovine serum were obtained from Hyclone Laboratories, Inc. (Logan, Utah). Dulbecco's phosphate-buffered saline (D-PBS) (with 1 mg/mL glucose and 3.6 mg/1 Na pyruvate, without phenol red), L-glutamine, hygromycin B, and Lipofectamine™ were obtained from 10 Life Technologies (Grand Island, NY). G418 sulfate was obtained from Calbiochem-Novabiochem Corp. (San Diego, CA). Capsaicin (8-methyl-N-vanillyl-6-nonenamide) was obtained from Sigma-AIdrich, Co. (St. Louis, MO). Fluo-4 AM (N-[4-[6-[(acet'loxy)methoxy]-2,7-difluoro-3-oxo-3H-xanthen-9-yl]-2-[2-[2-[bis[2-[(acetyloxy)methoxy]-2-oxyethyl]amino]-5-methylphenoxy]ethoxy]phenyl]-N-[2- 15 [(acetyloxy)methoxy]-2-oxyethyl]-glycine, (acetyloxy)methyl ester) was purchased from Molecular Probes (Eugene, OR). The cDNAs for the human VR1 receptor were isolated by reverse transcriptase-polymerase chain reaction (RT-PCR) from human small intestine poly A+RNA supplied by Clontech (Palo Alto, CA) using primers designed surrounding the initiation and termination 20 codons identical to the published sequences (Hayes et al Pain Vol. 88 pages 205-215, 2000). The resulting cDNA PCR products were subcloned into pCIneo mammalian expression vector (Promega) and fully sequenced using fluorescent dye-terminator reagents (Prism, Perkin-Elmer Applied Biosystems Division) and a Perkin-Elmer Applied Biosystems Model 3 73 DNA sequencer or Model 310 genetic analyzer. Expression plasmids encoding 25 the hVRl cDNA were transfected individually into 1321N1 human astrocytoma cells using Lipofectamine™. Forty-eight hours after transfection, the neomycin-resistant cells were selected with growth medium containing 800μ.g/mL Geneticin (Gibco BRL). Surviving individual colonies were isolated and screened for VR1 receptor activity. Cells expressing recombinant homomeric VR1 receptors were maintained at 37 °C in D-MEM containing 4 30 mM L-glutaraine, 300 u-g/mL G418 (Cal-biochem) and 10% fetal bovine serum under a humidified 5% CO2 atmosphere. 86 WO 2005/007642 PCT/US2004/02J836 The functional activity of compounds at the VR1 receptor was determined with a Ca influx assay and measurement of intracellular Ca2+ levels ([Ca2+]i). All compounds were tested over an 11-point half-log concentration range. Compound solutions were prepared in D-PBS (4x final concentration), and diluted serially across 96-well v-bottom tissue culture 5 plates using a Biomek 2000 robotic automation workstation (Beckman-Coulter, Inc., Fullerton, CA). A 0.2 μM solution of the VR1 agonist capsaicin was also prepared in D-PBS. The fluorescent Ca2+ chelating dye fluo-4 was used as an indicator of the relative levels offCa24] i in a 96-well format using a Fluorescence Imaging Plate Reader (FLIPR)(Molecular Devices, Sunnyvale, CA). Cells were grown to confluency in 96-well black-walled tissue 10 culture plates. Then, prior to the assay, the cells were loaded with 100 μL per well of fluo-4 AM (2 δM, in D-PBS) for 1-2 hours at 23 °C. Washing of the cells was performed to remove extracellular fluo-4 AM (2x1 mL D-PBS per well), and afterward, the cells were placed in the reading chamber of the FLIPR instrument. 50 μL of the compound solutions were added to the cells at the 10 second time mark of the experimental run. Then, after a 3 minute time 15 delay, 50 μL of the capsaicin solution was added at the 190 second time mark (0.05 μM final concentration)(final volume = 200 μL) to challenge the VR1 receptor. Time length of the experimental run was 240 seconds. Fluorescence readings were made at 1 to 5 second intervals over the course of the experimental run. The peak increase in relative fluorescence units (minus baseline) was calculated from the 190 second time mark to the end of the 20 experimental run, and expressed as a percentage of the 0.05 μM capsaicin (control) response. Curve-fits of the data were solved using a four-parameter logistic Hill equation in GraphPad Prism® (GraphPad Software, Inc., San Diego, CA), and IC50 values were calculated. The compounds of the present invention were found to be antagonists of the vanilloid receptor subtype 1 (VR1) receptor with IC505 from about 2200 nM to about 0.5 nM. In a 25 preferred range, compounds tested had ICsos from about 200 nM to about 1.0 nM. (a) In Vivo Data - analgesic effects Experiments were performed on 400 adult male 129J mice (Jackson Laboratories, Bar Harbor, ME), weighing 20-25 g and male Sprague-Dawley rats (Charles River, Wilmington, MA) weighing 200-300 grams were utilized. Animals were kept in a vivarium, maintained at 30 22 °C= with a 12 hour alternating light-dark cycle with food and water available ad libitum. All experiments were performed during the light cycle. Animals were randomly divided into separate groups of 6 animals each. Each animal was used in one experiment only and was 87 WO 2005/007642 PCT/US2004/02I836 sacrificed immediately following the completion of the experiment. All animal handling and experimental procedures were approved by an IACUC Committee. The antinociceptive test used was a modification of the abdominal constriction assay described in Collier, et al., Br. J. Pharmacol. Chemother. 32 (1968) 295-310. Each animal 5 received an intraperitoneal (i.p.) injection of 0.3 mL of 0.6% acetic acid in normal saline to evoke writhing. Animals were placed separately under clear cylinders for the observation and quantification of abdominal constriction. Abdominal constriction was defined as a mild constriction and elongation passing caudally along the abdominal wall, accompanied by a slight twisting of the trunk and followed by bilateral extension of the hind limbs. The total 10 number of abdominal constrictions was recorded from 5 to 20 minutes after acetic acid injection. The EDsos were determined based on the i.p. injection. The other antinociceptive test used was Complete Freund's Adjuvant-induced Thermal Hyperalgesia (CFA) assay described in Pircio et al (Eur J Pharmacol. Vol. 31(2) pages 207-15,1975). Chronic inflammatory hyperalgesia was induced in one group of rats 15 following the injection of complete Freund's adjuvant (CFA, 50%, 150 μl) into the plantar surface of the right hindpaw 48 hours prior to testing. Thermal nociceptive thresholds were measured in three different groups of rats. The EDsos were determined based on the oral administration.. The compounds of the present invention tested were found to have antinociceptive 20 effects with ED505 from about 1 mg/kg to about 500 mg/kg. The in vitro and in vivo data demonstrates that compounds of the present invention antagonize the VRI receptor and are useful for treating pain. Compounds of the present invention are also useful for ameliorating or preventing additional disorders such as, but not limited to, infammatory thermal hyperalgesia, bladder 25 overactivity, and urinary incontinence as described by Nolano, M. et al., Pain 81 (1999) 135; Caterina, M.J. and Julius, D., Annu. Rev. Neurosci. 24, (2001) 487-517; Caterina, M.J. et al., Science 288 (2000) 306-313; Caterina, MJ. et al., Nature 389 (1997) 816-824; Fowler, C. Urology 55 (2000) 60; and Davis, J. et al., Nature 405 (2000) 183-187. The present invention also provides pharmaceutical compositions that comprise 30 compounds of the present invention. The pharmaceutical compositions comprise compounds of the present invention formulated together with one or more non-toxic pharmaceutically acceptable carriers. 88 WO 2005/007642 PCT/US2004/021836 The pharmaceutical compositions of this invention can be administered to humans and other mammals orally, rectally, parenterally, intracistemally, intravaginally, topically (as by powders, ointments or drops), bucally or as an oral or nasal spray. The term "parenterally," as used herein, refers to modes of administration, which include intravenous, 5 intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion. The term "pharmaceutically acceptable carrier," as used herein, means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. Some examples of materials which can serve as pharmaceutically acceptable 10 carriers are sugars such as, but not limited to, lactose, glucose and sucrose; starches such as, but not limited to, com starch and potato starch; cellulose and its derivatives such as, but not limited to, sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as, but not limited to, cocoa butter and suppository waxes; oils such as, but not limited to, peanut oil, cottonseed oil, safflower oil, 15 sesame oil, olive oil, corn oil and soybean oil; glycols; such as propylene glycol; esters such as, but not limited to, ethyl oleate and ethyl laurate; agar; buffering agents such as, but not limited to, magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as, but not limited to, sodium lauryl sulfate and 20 magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. Pharmaceutical compositions of this invention for parenteral injection comprise pharmaceutically acceptable sterile aqueous or nonaqueous solutions, dispersions, 25 suspensions or emulsions as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), vegetable oils (such as olive oil), injectable organic esters (such as ethyl oleate) and suitable mixtures thereof. Proper fluidity 30 can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. 89 WO 2005/007642 PCT/US2004/021836 These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid and the like. It may also be desirable to include isotonic 5 agents such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the inclusion of agents, which delay absorption such as aluminum monostearate and gelatin. In some cases, in order to prolong the effect of the drug, it is desirable to slow the absorption of the drug from subcutaneous ,or intramuscular injection. This can be 10 accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. 15 Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in 20 liposomes or microemulsions that are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium just prior to use. 25 Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound may be mixed with at least one inert, pharmaceutically acceptable carrier or excipient, such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, 30 polyvinylpyrrolidone, sucrose and acacia; c) humectants such as glycerol; d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) solution retarding agents such as paraffin; f) absorption 90 WO 2(105/007642 PCT/US2004/021836 accelerators such as quaternary ammonium compounds; g) wetting agents such as cetyl alcohol and glycerol monostearate; h) absorbents such as kaolin and bentonite clay and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the 5 dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such carriers as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The solid dosage forms of tablets, dragees, capsules, pills and granules can be 10 prepared with coatings and shells such as enteric coatings and other coatings well-known in the pharmaceutical formulating art. They may optionally contain opacifying agents and may also be of a composition such that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. 15 The active compounds can also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned carriers. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for 20 example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan and mixtures thereof. 25 Besides inert diluents, the oral compositions may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring and perfuming agents; Suspensions, in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, 30 microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, tragacanth and mixtures thereof. Compositions for rectal or vaginal administration are preferably suppositories which 91 WO 2005/007642 PCT/US2004/021836 can be prepared by mixing the compounds of this invention with suitable non-irritating carriers or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. 5 Compounds of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals which are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. The present 10 compositions in liposome form can contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients and the like. The preferred lipids are natural and synthetic phospholipids and phosphatidyl cholines (lecithins) used separately or together. Methods to form liposomes are known in the art. See, for example, Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 et 15 seq. Dosage forms for topical administration of a compound of this invention include powders, sprays, ointments and inhalants. The active compound may be mixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives, buffers or propellants that may be required. Opthalmic formulations, eye ointments, powders and 20 solutions are also contemplated as being within the scope of this invention. Actual dosage levels of active ingredients in the pharmaceutical compositions of this invention can be varied so as to obtain an amount of the active compound(s) which is effective to achieve the desired therapeutic response for a particular patient, compositions and mode of administration. The selected dosage level will depend upon the activity of the 25 particular compound, the route of administration, the severity of the condition being treated and the condition and prior medical history of the patient being treated. When used in the above or other treatments, a therapeutically effective amount of one of the compounds of the present invention can be employed in pure form or, where such forms exist, in pharmaceutically acceptable salt, ester or prodrug form. The phrase 30 "therapeutically effective amount" of the compound of the invention means a sufficient amount of the compound to treat disorders, at a reasonable benefit/risk ratio applicable to any medical treatment It will be understood, however, that the total daily usage of the 92 JVO 2005/007642 PCT/US2004/021836 expounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgement. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of the specific compound 5 employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts. 10 The term "pharmaceutically acceptable salt," as used herein, means salts derived from • inorganic or organic acids. The salts can be prepared in situ during the final isolation and purification of compounds of formula (I-VII) or separately by reacting the free base of a compound of formula (I-VII) with an inorganic or organic acid. Representative acid addition salts include, but are not limited to, acetate, adipate, alginate, citrate, aspartate, benzoate, 15 benzenesulfonate, bisulfate, butyrate, camphorate, camphorsufonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, dihydrochloride, hydrobromide, hydroiodide, 2-hydroxyethansulfonate (isethionate), lactate, maleate, fumarate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, sulfate, (L) 20 tartrate, (D) tartrate, (DL) tartrate, thiocyanate, phosphate, glutamate, bicarbonate, p-toluenesulfonate, and undecanoate. The term "pharmaceutically acceptable ester," as used herein, means esters of compounds of the present invention which hydrolyze in vivo and include those that break down readily in the human body to leave the parent compound or a salt thereof. Examples of 25 pharmaceutically acceptable, non-toxic esters of the present invention include Ci-to-Ce alkyl esters and C5-10-C7 cycloalkyl esters, although Ci-to-C4 alkyl esters are preferred. Esters of the compounds of formula (I-VII) may be prepared according to conventional methods. The term "pharmaceutically acceptable amide," as used herein, means to non-toxic .amides of the present invention derived from ammonia, primary Cj-to-Cg alkyl amines and 30 secondary Cj-to-Ce dialkyl amines. In the case of secondary amines, the amine may also be in the form of a 5- or 6-membered heterocycle containing one nitrogen atom. Amides derived from ammonia. Cj-to-C3 alkyl primary amides and Cj-to-C2 dialkyl secondary 93 WO 2005/007642 PCT/US2004/021836 amides are preferred. Amides of the compounds of formula (I-VII) may be prepared according to conventional methods. The term "pharmaceutically acceptable prodrug" or "prodrug,"as used herein, represents those prodrugs of the compounds of the present invention which are, within the 5 scope of sound medical judgement, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like. Prodrugs of the present invention may be rapidly transformed in vivo to compounds of formula (I-VII), for example, by hydrolysis in blood. The present invention contemplates compound of formula (I-VII) formed by 10 synthetic means or formed by in vivo biotransformation. The compounds of the invention can exist in unsolvated as well as solvated forms, including hydrated forms, such as hemi-hydrates. In general, the solvated forms, with pharmaceutically acceptable solvents such as water and ethanol among others are equivalent to the unsolvated forms for the purposes of the invention. 15 The total daily dose of the compounds of this invention administered to a human or lower animal may range from about 0.01 to about 150 mg/kg/day. For purposes of oral administration, more preferable doses can be in the range of from about 0.1 to about 150 mg/kg/day. If desired, the effective daily dose can be divided into multiple doses for purposes of administration; consequently, single dose compositions may contain such 20 amounts or submultiples thereof to make up the daily dose. 21 22 23 94 WO 2005/007642 PCT/US2004/02183f> WHAT IS CLAIMED IS: 1. A compound of formula (I) H 5 (I), or a pharmaceutically acceptable salt or prodrug thereof, wherein A is XiisNorCRi; 10 X2isNorCR2; X3isS,OorN; R is absent or O; R] is hydrogen, lower alkoxy, lower alkenyl, lower alkyl, lower alkylthio, lower alkynyl, lower haloalkoxy, lower haloalkyl, lower haloalkylthio, halogen, hydroxy, mercapto, 15 nitro, RARBNS(0)2- or RARBN-; R2, R3, and R4 are independently hydrogen or halogen; R7 is hydrogen, alkenyl, alkoxy, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkoxycarbonylalkyl. alkylsulfonyl, alkylthio, alkynyl, aryl, arylalkyl, aryloxy, arylthio, cyanoalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, cycloalkylthio, haloalkoxy, haloalkyl, 20 haloalkylsulfonyl, haloalkylthio, halogen, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, -RCRDN-, (RARBN)carbonyl-, (RARBN)sulfonyI-; or RAS(0)>; R6 and R8 are independently hydrogen, lower alkenyl, lower alkoxy, lower alkyl, lower alkylthio, lower alkynyl. lower haloalkoxy, lower haloalkyl, lower haloalkylthio, 25 halogen, hydroxy, mercapto, or RARBN~; alternatively, R7 and Re taken together with the atoms they are attached can form a ring selected of 2;2;3;3-teti-afluoro-2,3-dihydro-benzo[l,4]dioxinyl;fromthe group consisting 2;2;3;3-teti-afluoro-2,3-dihydro-benzo[l,4]dioxinyl;fromthe group consisting 95 WO 2005/007642 PCT/US2004/021836 2,3-tetrahydro-berizo[l,4]dioxinyl; 2,2-difluoro-benzo[l,3]dioxolyl; and 2,2-dihydro-benzo[l,3]dioxolyl; RA and RB are independently alkyl, hydrogen, haloalkyl, or heterocycle; Re and RD are independently hydrogen, alkenyl, alkoxycarbonyl, alkyl, alkylcarbonyl, 5 alkynyl, or (NRARB)carbonyl; Lis 10 -j-N Rl1-14 , RlM4 > R11-14 , Rn-14 > or "11-14 » — is absent or a single bond; and Ri i, R12, Ru, and RJ4 are independently hydrogen, alkoxy, alkyl, or hydroxy. The compound according to claim 1 of formula (II) 'Xl- ^ 14 fYl Rs O R4 00, or a pharmaceutically acceptable salt or prodrug thereof. 15 3. The compound according to claim 2 wherein — is a single bond; XiisCR,; X2 is CR2; 20 R] is lower haloalkyl, halogen, or RARBNS(0)2-; R2, R3; and R4 are hydrogen; 96 WO 2005/007642 PCT/US2004/021836 R7 is alkoxy, alkyl, alkylthio, alkylcarbonyl, hydroxyalkyl, alkylcarbonylalkyl, cycloalkyl, haloalkoxy, haloalkyl, haloalkylsulfonyl, haloalkylthio, halogen, RCRDN-; or RAS(0)2-; R11, R12, R13, and RH are hydrogen; and 5 Re and RD are independently hydrogen or alkyl. 4. The compound according to claim 3 that is N-(4-tert-but}'lphenyl)-3,-chloro-3,6-dihydro-2H-l,2,-bipyridine-4-carboxamide; 3'-chloro-N-(4-methylphenyl)-3,6-dihydro-2H-l,2'-bipyridine-4-carboxamide; 10 3,-chIoro-N-(4-methoxyphenyI)-3,6-dmydro-2H-l,2'-bipyridine^-carboxarnide; 3'-chloro-N-(4-fluorophenyl)-3,6-dihydro-2H-l,2,-bipyridirje-4-carboxamide; N-(4-bromophenyl)-3'-chloro-3]6-dihydro-2H-l,2'-bipyridine-4-carboxamide; 3'-chloro-N-[4-(trifluoromethoxy)phenyl]-3,6-dihydro-2H-l,2,-bipyridine-4- carboxamide; 15 3'-chloro-N-(4-ethylphenyl)-3,6-dihydro-2H-l ,2'-bipyridine-4-carboxamide; 3'-chloro-N-(4-isopropylphenyl)-3J6-dihydro-2H-1.2'-bipyridine-4-carboxamide; 3'-chloro-N-(4-propoxyphenyl)-3,6-dihydro-2H-l,2,-bipyridine-4-carboxamide; 3'-cliloro-N44-(methylthio)phenyl]-3,6-dihydro-2H-l,2'-bipyridine-4-carboxamide; chloro-N-(3-fluoro-4-methylphenyl)-3,6-dihydro-2H-1,2-bipyridine-4- 20 carboxamide; 3'-chloro-N-[4-(trifluoromethylJphenylj-S^-dihydro^H-l^'-bipyridine^-carboxamide; 3,-chloro-N-[4-(dimemylamino)phenyl]-3,6-dihydro-2H-l,2,-bipyridine-4- carboxamide; 25 3'-cUoro-N-[4-(diethylamino)phenyl]-3J6-dmydro-2H-l,2,-bipyridine-4^arboxarriide; N-(4-tert-butylphenyl)-l-(3-chloro-2-pyridinyl)-(cis)-3-hydroxy-4-piperidinecarboxamide; N-(4-tert-butylphenyl)-l-(3-chIoro-2~pyridinyl)-(trans)-3-hydroxy-4' piperidinecarboxamide; 30 l-(3-chloro-2-pyridinyl)-4-hydroxy-N-[4-(trifluoromethyl)phenyl]-4- piperidinecarboxamide. 97 WO 2005/007642 PCT/US2004/021836 N-(4-tert-butylphenyl)-3'-(trifluoromethyl)-3)6-dihydro-2H-l,2'-bipyridine-4-carboxamide; N-(4-chlorophenyl)-3'-(trifluoromethyl)-356-dihydro-2H-1..2'-bipyridine-4- carboxamide; 5 N-[4-(trifluoromethoxy)phenyl]-3,6-dihydro-2H-1,2-bipyridine-4- 4-carboxamide; 3'-(trifiuoromethyI)-N-{44(trifluoromethyl)thio]phenyl}-3,6-dihydro-2H-ls2,-bipyridine-4-carboxamide; 3'-(trifluoromethyl)-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-3)6-dihydro-2H-l,2'-10 bipyridine-4-carboxamide; N-(3-fIuoro4-me%lphenyl)0'-(trifluoromethyl)-3,6-dihydro-2H-U2'-bipyrid]me-4-carboxamide; 3'-Chloro-3.,6-dihydro-2i/-[l ,2']bipyridiiiyl-4-carboxylic acid (4-bromo-3-fluoro- phenyl)-amide; 15 3'-Chloro-3,6-dihydro-2i/-[l)2,]bipyridinyl-4-carboxylicacid(4-bromo-3-methyl- phenyl)-amide; 3'-Trifluoromethyl-3,6-dihydro-2H-[la2']bipyridinyl-4-carboxylicacid (4-chloro-phenyl)-amide; 3,-Trifluoromethyl-3>6-dihydro-2H-[l}2,]bipyridmyl-4-carboxylicacid(4- 20 trifluoromethylsulfanyl-phenyl)-amide; 3'-Trifluoromethyl'3,6-dihydro-2H-[1,2,]bipyridinyl-4-carboxylicacid(4-trifluoromethoxy-phenyl)-amide; 3,-Chloro-3)6-dihydro-2ii/-[l,2']bipyridinyl-4-carboxylicacid(4-bromo-3-chloro- phenyl)-amide; 25 3'-CMoro-3,6-dihydro-2#41,2']bipyridinyl-carboxylic acid (4-bromo-3- trifluoromethyl-phenyl)-amide; 3'-Chloro-3s6-dihydro-2//-[l 52']bipyridinyl-4-carboxylic acid (4-chloro-3-fluoro-phenyl)-amide; 3'-Chloro-3)6-dihydro-2if-[lJ2']bipyridinyl-4-carboxylicacid(3,4-dichJoro-phenyl)-30 amide; 3,-Chloroo;6-dihydro-2if-[l)2,]bipyridinyl-4-carboxylicacid(4-chloro-3-methyl-phenyl)-amide; 9B WO 2005/007642 PCT/US2004/021836 3'-Chloro-3,6-dihydro-2H-[l ,2]bipyridinyl-carboxylic acid (4-chloro-3-trifluororaethyl-phenyl)-amide; 3'-Chloro-3J6-dihydro-2if-[l,2']bipyridinyl-4-carboxylicacid(4-difluoromethyoxy- phenyl)-amide; 5 3'-ChIoro-3,6-dihydro-2//-[l)2']bipyridiiiyl-4-carboxylicacid[4-(l)l,2s2-tetrafluoro- ethoxy)-phenyl]-amide; 3,-Chloro-3,6-dihydro-2if-fl,2,]bipyridinyl-4-carboxylicacid(3-chloro-4-methyl-phenyl)-amide; 3*-Chloro-3)6-dihydro-2H-[l,2,]bipyridinyl-4-carboxylicacid(3--bromo-4-methyl- 10 phenyl)-amide; 3-Chloro-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylic acid (4-methyl-3-trifluorornethyl-phenyl)-amide; 3-Chloro-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylic acid (4- trifluoromethylsulfanyl-phenyl)-amide; 15 3,-Chloro-3!6-dihydro-2H-[1,2']bipyridinyl-4-carboxylic acid (3-fluoro-4- trifluoromethyl-phenyl)-amide 3'-Chloro-3;6'dihydro-2H-[l ,2']bipyridinyl-4-carboxylic acid (3,4-dimethyl-phenyI)-amide; 3'-Chloro-3,6-dihydro-2H-[l,2]bipyridinyl-carboxylic acid (4-ter/-butyl-3-fluoro-20 phenyl)-amide; 3'-Trifluoromethyl-3,6-dihydro-2H-[1,2]bipyridinyl-carboxylic acid (4-chloro-3-f!uoro-phenyl)-amide; 3'-Trifluoromethyl-3;6-dihydro-2//-[U2,]bipyridinyl-4-carboxylicacid(4-re;-/-butyl- 3-fluoro-phenyl)-amide; 25 3'-TrifluoromethyI-3,6-dihydro-2H-[1.2,]bipyridinyl-4-carboxylic acid [4-(l- hydroxy-1 -methyl-ethyl)-phenyl]-amide; 3,-Ch]oro-3J6-dihydro-2H-[l,2,]bipyridinyl-4-carboxylicacid [4-(ethyl-isopropyl-amino)-phenyl]-amide hydrochloride; 3'-Chloro-3J6-diliydro-2//-[l,2,]bipyridinyl-4-carboxylicacid(4-cyclopropyl- 30 phenyl)-amide; 3'-Chloro-3J6-dihydro-2H-[L2']bipyridinyl-4-carboxylicacid[4-(2s2)2-trifluoro-l-hydioxy-1 -trifluoromethyI-ethyl)-phenyl]-amide; 99 WO 2005/007642 PCT/US2O04/O2183fi Chloro-3,6-dihydro-2H-[l)2']bipyridinyl-4-carbox7licacid[4-(2,2-dichJoro-l-methyI-cyclopropyl)-phenyl]-amide; 3,-Trifluoromethyl-3s6-dihydro-2i/-[l,2>]bipyridinyl-4-carboxylic acid (3,4- difluorophenyl)-amide; 5 2-Methyl-2-{4-[(3'4rifluoromethyl-3,6-dihydro-2H-[1,2]bipyridinyl-4-carbonyl)- amino]-phenyl}-propionic acid methyl ester; 3,-TrifluoromethyI-3,6-dihydro-2//-[l32']bipyridinyl-4-carboxyb'cacid[4-(2-hydroxy-1,1 -dimethyl-ethyl)-phenyl]-amide; 3,-Trifluoromethyl-3s6-dihydro-2i/-[l^,]bipyridinyl-4-carboxylicacid(4-acetyl- 10 phenyl)-amide; 44(3'-Trifluoromethyl-3,6-dihydro-2//'-[l,2i]bipyridinyM-caitonyl)-amino]-benzoic acid methyl ester; 3,-Trifluoromethyl-3J6-dihydro-2//-[l,2']bipyridinyl--4-carboxylicacid(4- trifluoromethyI-phenyl)-amide; 15 3-Trifluoromethyl-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylic acid (4-tert- butylsulfanyl-phenyl)-amide; 3'-Trifluoromethyl-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylicacid [4-(2-methyI-propane-2'SuIfonyl)-phenyl]-amide; 3'-Chloro-3,6-dihydro-2#-[l)2']bipyridinyl-4-carboxylic acid (4- 20 trifluoromethanesulfonyl-phenyl)-amide; 3-Chloro-3,6-dihydro-2H-[1,2]bipyridinyl-4-carboxylic acid[4-(cyano-dimethyl-methyl)-phenyl]-amide; 3,-Trifluoromethyl-3,6-dihydro-2^/"-[lJ2,]bipyridinyl-4-carboxylicacid [4-(cyano- dimethyl-methyl)-phenyl]-amide; 25 3'-Trifluoromethyl-3,6-dihydro-2/f-[lJ2']bipyridmyl-4-carboxylic acid (3-chJoro-4- trifluoromethylsulfanyl-phenyl)-amide; 3 '-Trifluoromethy]-3,6-dihydro-2#-[l ^'JbipyridinyM-carboxylic acid (4-dimethylsulfamoyl-phenyl)-amide; 3,-Trifluoromethyl-3J6-dihydro-2^-tl,2,]bipyridinyl-4-carboxyIicacid [4- 30 (piperidine-l-sulfonyI)-phenyl]-amide; 3'-Chloro-3>6-dihydro-2i/-[l,2']bipyridinyl-4-carboxylie acid (4-methanesulfonyl-phenyl)-amide; 100 WO 2005/007642 PCT/US2004/02J836 3'-Dimethylsulfamoyl-3J6-dihydro-2^41,2,]bipyridmyl-4-carboxylicacid(4-i'e/-N butyl-phenyl)-amide; 3,-Dimethylsulfamoyl-3s6-dihydro-2//-[l,2']bipyridinyl-4-carboxylicacid(4~chloro- phenyl)-amide; or 5 3,-Dimethylsulfain-oyJ.-3,6-dihydro-2K-[l)2,]bipyridinyl-4-carboxylicacid(4- trifluoromethoxy-phenyl)-amide. 5. The compound according to claim 3 that is 3'-chloro-N-(4-chlorophenyl)-3,6-dihydro- 2H-1,2'-bipyridine-4-carboxamide. 10 6. The compound according to claim 2 wherein — is a single bond; Xi is CRi; X2 is CR2; 15 R| is lower haloalkyl or halogen; R2s R3, and R4 are hydrogen; R7 is aryl or aryloxy; and R11, R12, Rn: and R!4 are hydrogen. 20 7. The compound according to claim 6 that is 3,-chloro-N-(4-phenoxyphenyl)-3,6-dihydro-2H-l,2,-bipyridine-4-carboxamide; or N-lsr-biphenyl-4-yl-3'-chloro-3J6-dihydro-2H-lJ2'-bipyridine-4-carboxamide. 25 8. The compound according to claim 2 wherein — is a single bond; XiisCRi; X2 is CR2; Ri, is lower haloalkyl or halogen; 30 R2, R3, and R4 are hydrogen; R7 is heterocycle; and Rn, R]2j R13, and R14 are hydrogen. 101 WO 2005/007642 PCT/US2004/021836 9. The compound according to claim 8 that is 3'-cMoro-N-[4-(l-piperidinyl)phenyl]-3,6-o^ya^o-2H-l)2'-bipyridine-4-carboxamide; 3'-chloro-N-[4-(4-morpholinyl)phenyI]-336-dihydro-2H-l,2l-bipyridine-4- 5 carboxamide; N44-(l-a2epanyl)phenyl]-3'-cMom-3?6-dihydro-2H-l,2r-bipyridine-4-carboxamide; 3*-Chloro-3)6-dihydro-2i:/-[l,2']bipyridinyl-4-carboxylicacid(4-a2epan-l-y]-phenyl)-amide; 3'-Trifluoromemyl-336-o^ydro-2i/-[l,2']bipyridinyl-4-carboxylicacid(4-azepan-l-10 yl-phenyl)-amide; S'-Trifluoromemyl-3,6-dihydro-2H-[1,2]bipyridinyl-4--carboxylicacid [4-(8-aza-bicyclo[3.2.1]oct-8-yl)-phenyl]-amide; 3'-Trifluoromethyl-3,6-dihydro-2i/-[l,2']bipyridinyl-4-carboxylicacid[4-(8-aza- bicyclo[3.2.1]oct-8-yl)-3-fluoro-phenyl]amide; 15 3'-Trifluoromethyl-3,6-dihydro-2#-[l ^']bipyridinyl-4-carboxylic acid [4-(8-aza- bicyclo[3.2.1 ]oct-8-yl)-3,5-difluoro-phenyl]amide; or 3'-Chloro-3,6-dihydro-2/f-[ls2']bipyridinyl-4-carboxylicacid [4-(8-aza-bicyclo[3.2.1Joct-S-yl)-3,5-difluoro-phenyl]-amide. 20 10. The compound according to claim 2, wherein R7 and R8 taken together with the atoms they are attached can form a ring selected from the group consisting of 2J2,3,3-tetrafluoro-2,3-dihydro-benzo[l,4]dioxinyl; 2,3-tetrahydro-benzo[l,4]dioxinyl; 2,2-difluoro-benzo[l,3]dioxolyl; and 2,2-dihydro-benzo[l,3]dioxolyl. 25 11. The compound according to claim 10 that is 3'-CMoro-3J6-dihydro-2i/-[l,2,]bipyridinyl-4-carboxylicacid(2J2)3;3-tetrafluoro-2.3-dihydro-benzo[l,4]dioxin-6-yl)-amide; 3'-Trifluoromethyl-3,6-dihydro-2//-[l,2']bipyridinyl-4-carboxylic acid (2,2-difluoro- benzo[l,3]dioxoI-5-yl)-amide; 30 3,-ChIoro-3)6-dihydro-2^-[lJ2,]bipyridinyl-4-^-rboxyhcacid(2,2-difluoro- benzo[l,3]dioxol-5-yl)-amide. 102 WO 2005/007642 PCT/US2004/021836 "2: The compound according to claim 2 wherein — is a single bond; XiisCRi; X2 is CR2; 5 R.! is lower haloalkyl or halogen; R2, &3> and R4 are hydrogen; R6 is lower alkyl, lower haloalkyl, or halogen; and R7, R8, R11, Rj2, Ri3, and Ri4 are hydrogen. 10 13. The compound according to claim 12 that is N-(3-tert-butylphenyl)-3'-chloro-3,6-dihydro-2H-l,2-bipyridine-4-carboxamide; or 3,-chloro-N-(3-fluorophenyl)-3.6-dihydro-2H-l,2'-bipyridine-4-carboxamide. 15 14. The compound according to claim 2 wherein — is a single bond; XiisN; X2 is CR2; R2, R3, and R4 are hydrogen; 20 R7 is alkoxy, alkyl, alkylthio, haloalkoxy, haloalkyl. haloalkylsulfonyl, haloalkylthio, halogen, or RCRDN-; RH, R]2, R-13, and R14 are hydrogen; and Re and RD are independently hydrogen or alkyl. 25 15. The compound according to claim 12 that is N-(4-chlorophenyl)-l-pyrimidin-2-yl-l,2,3,6-tetrahydropyridine-4-carboxamide; l-pynmidm-2-yl-N-{4-[(trifluoromemyl)mlo]phenyl}-l,2,3)6^etrahydropyridine-4-carboxamide; l-pyrimidm-2-yl-N-{4-[(tTifluoromemyl)sulfonyl]phenyl}-lJ2,3,6-tetrahydropyridme-30 4-carboxamide; l-pyrimidin-2-yl-l ,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-/e/-/-butyl-phenyI)-amide; 103 WO 2005/007642 PCT/US2004/023836 1 -pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-chloro-phenyl)-amide; l-pyrimidin-2-yl-l,233)6,etrahydr(>-pyridine-4-carbox7licacid(4-trifluoromethyoxy- phenyl)-amide; 5 l-pyrimidin-2-yI-l,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4- trifluoromethyIsuifanyI-phenyl)-amide; l-pyrimidin-2-yl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4- trifluoromethanesulfonyl-phenyl)-amide; 1 -pyrimidin-2-yl-1 ,2,3?6-tetrahydro-pyridine-4- carboxylic acid (4-ferr-butyl-3-fluoro-phenyl)-amide; 10 1 -pyrimidin-2-yI- l,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-trifluoromethyl- phenyl)-amide; l-pyrimidk-2-yl-I^,3s6-tetraJiydro-pyridine-4-carboxylicacid(4-chloro-3-fluoro-phenyl)-amide; 2-Methyl-2-{4-[(l-pyrimidin-2-yI-l;2,3»6-tetrahydro-pyridine-4-carbonyl)-amino]- 15 phenyl}-propionic acid methyl ester; 1 -pyrimidin-2-yl-l ,2,3,6-tetrahydro-p>Tidine-4-carboxyIic acid (4-acetyI-phenyl)-amide; 4-[(l-Pyrimidin-2-yl-l,2,3)6-tetrahydro-pyridme4-carbonyI)-amino]-ben2oicacid methyl ester; 20 l-pyrimidin-2-yl-l,2,3,6-tetrahydro-pyridine-4-carboxylic acid [4-(2-methyl-propane- 2-sulfonyl)-phenyI]-amide; l-pyrimidin-2-yl-l?2,3,6-tetrahydro-pyridine-4-carboxylicacid(4-rerr-butylsulfanyl-phenyl)-amide; or 1 -(4-Methoxy-pyrimidin-2-yl)-1,2,3s6-tetrahydro-pyridine-4-carboxylic acid (4- 25 trifluoromethyl-phenyl)-amide. 16. The compound according to claim 2 wherein — is a single bond; XjisN; 30 X2 is CR2; R2. R3, and Rj are hydrogen; R? is heterocycle; 104 WO 2005/007642 R11, R12, P-13, and R14 are hydrogen; and Re and RD are independently hydrogen or alky]. PCT/US2004/021836 17. The compound according to claim 16 that is 5 l-Pyrimidin-2-yl-l,2s3,6-tetrahydro-pyridine-4-carboxylic acid [4-(8-aza- bicyclo[3.2.1]oct-8-yl)-3-fluoro-phenyl]-amide; 1 -Pyrimidin-2-yl-1,2,3 ,6-tetrahydro-pyridine-4-carboxylic acid [4-(8-aza-bicyclo[3.2.1]oct-8-yl)-3,5-difluoro-phenyl]-amide;or l-Pyrimidin-2-yl-l)2,3,6-tetrahydro-pyridine-4-carboxylic acid (4-azepan-l-yl- 10 phenyl)-amide. 18. A compound of formula (III) 15 20 25 (III) — is a«single bond; X, is CRi; X2 is CR2; Ri is hydrogen, lower haloalkyl or halogen; R2, R3, R4, and R& are hydrogen; Rs is alkyl, hydrogen, halogen, alkoxy, or haloalkoxy; R5 is alkoxy, alkyl, alkylthio, cycloalkyl, haloalkoxy, haloalkyl, haloalkylsulfonyl, haloalkylthio, halogen, RCRDN-; or RAS(0)2-; R] u R12, R]3) and R14 are hydrogen; and RA, RC and RD are independently hydrogen or alkyl. 19. The compound according to claim 18 that is 105 WO 2005/007642 PCT/US2004/02I836 3'-ChIoro-3,6-dihydro-2^-[l,2']bipyridinyl-4-carboxylicacid(4-bromo-2-chloro- phenyl)-amide; 3,-Chloro-3,6-dihydro-2i/-[lJ2']bipyridinyl-4-carboxyIicacid(4-bromo-2-fluoro- phenyl)-amide; 5 3,-ChIoro-336-dihydro-2//'-[l,2']bipyridinyl-4-carboxylic acid (4-bromo-2-methyl- phenyl)-amide; 3,-Chloro-3,6-dihydro-2/f-[l,2']bipyridinyl-4-carboxyIicacid(2-fluoro-4-iodo-phenyl)-amide; 3,-Chloro-3)6-dihydro-2//"-[l,2']bipyridinyl-4-carboxyIicacid(4-chloro-2- 10 trifluoromethyl-phenyl)-amide; 3,-Trifluorome%l-3)6-dihydro-2i/-[l,2']bipyridinyl-4-carboxylicacid(4-terr-butyl-2-chJoro-phenyl)-amide; 3,-Chloro-3,6-dihydro-2/r-[ls2s]bipyridinyI-4-carboxylicacid(4-^^-butyJ-2-fiuoro- phenyl)-amide; or 15 3,-ChIoro-3s6-dihydro-2H-[3,2']bipyridinyI-4-carboxyIicacid(4-ch]oro-2-fluoro- phenyl)-amide. 20. The compound according to claim 1 of formula (IV) Rs X,XYN-V H Rr<*H Rl1"14 R4 20 (IV), or a.pharmaceutically acceptable salt or prodrug thereof. 21. The compound according to claim 20 wherein X1 is CRi; 25 X2 is CR2; Ri is lower haloalkyl or halogen; R2, R3, and R4 are hydrogen; 106 WO 2005/007642 PCT/US2004/021836 R7 is alkoxy, alkyl, alkylthio, haloalkoxy, haloalkyl, haloalkylthio, halogen, or RCRDN-; R11, Ri2, R13, and R14 are hydrogen; and Re and RD are independently hydrogen or alkyl. 5 22. The compound according to claim 21 that is N-(4-tert-butylphenyl)-3-(3-chloro-2-pyridinyl)-3,8-dia2abicyclo[3.2.1]octane-8- carboxamide; 3-(3-chloro-2-pyridinyl)-N-(3,4-dichlorophenyl)-3s8-diazabicyclo[3.2.1]octane-8- 10 carboxamide; 3-(3-chIoro-2-pyridinyl)-N-[4-(trifluoromethyl)phenyl]-3)8-diazabicyclo[3.2.1 ]octane-8.-carboxamide; 3-(3-chIoro-2-pyridinyl)-N-(4-fluorophenyl)-3s8-diazabicyclo[3.2.1]octane-8- carboxamide; 15 N-(4-chlorophenyl)-3-(3-chIoro-2-pyridinyl)-358-diazabicyclo[3.2.1]octane-8- carboxamide; N-(4-bromophenyl)-3-(3-chloro-2-pyridinyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxamide; 3-(3-chloro-2-pyridinyl)-N-(4-iodophenyI)-3s8-diazabicyclo[3.2.1]octane-8- 20' carboxamide; N-(4-butylphenyl)"3-(3-chloro-2-pyridinyl)-3)8-diazabicyclo[3.2.1]octane-8-carboxamide; 3-(3-chloro-2-pyridinyI)-N-(4-isopropylphenyl)-3)8-diazabicyclo[3.2.1]octane-8- carboxamide; or 25 3-(3-chloro-2-pyridinyl)-N-{4-[(trifluoromethyl)thio]phenyl}-3,8- diazabicyclo[3.2.1 ]octane-8-carboxamide. 23. The compound according to claim 20 wherein XiisCRi; 30 X2 is CR2; Ri is lower haloalkyl or halogen; R2s R3, and R4 are hydrogen; 107 WO 2005/007642 PCT/US2004/021836 R$ is lower alkyl, lower haloalkyl, or halogen; and R7, R8 R11, R12, R13, and Ku are hydrogen. 24. The compound according to claim 23 that is 3-(3-chloro-2-pyridinyl)-N-[3- 5 (trifluoromethyl)pheny l]-3,8-diazabicyclo[3.2.1 ]octane-8-carboxamide. 25. The compound according to claim 1 of formula (V) N N' ^ "Re *V^ H I J. K11-1 Re R_—\ ^jN 14 R4 (V), 10 or a pharmaceutically acceptable salt or prodrug thereof. 26. The compound according to claim 25 wherein XiisCRi; X2 is CR2: 15 Ri is lower alkyl or halogen; R2, R3, and R4 are hydrogen; R7 is alkoxy, alkyl, alkylthio, haloalkoxy, haloalkyl, haloalkylthio, halogen, or RCRDN-; R11, R12, R13 and R14 are hydrogen; and 20 Re and RD are independently hydrogen or alkyl. 27. The compound according to claim 26 that is N-(4-tert-buri4phenyl)-8-(3-chloro-2-pyridinyl)-3,8-diazabicyclo[3.2.1]octane-3- carboxamide; or 25 3-chloro-2-p3ddmyI)-N-[4-(rrifluoromethyl)phenyl]-3,8-diazabicyclo[3.2.1]octane-3- carboxamide. 108 WO 2005/007642 PCT/US2004/021836 28. The compound according to claim 1 of formula (VI) RT^X: wherein 5 X3 is S; R2, and R3 are independently hydrogen or halogen; R7 is hydrogen, alkenyl, alkoxy, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkoxycarbonylalkyl, alkylsulfonyl, alkylthio, alkynyl, aryl, arylalkyl, aryloxy, arylthio, cyanoalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, cycloalkylthio, haloalkoxy, haloalkyl, 10 haloalkylsulfonyl, haloalkylthio, halogen, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, RCRDN-, (RARBN)carbonyl-, (RARBN)sulfonyl-; or RAS(0)2-; R6 and R8 are independently hydrogen, lower alkenyl, lower alkoxy, lower alkyl, lower alkylthio, lower alkynyl, lower haloalkoxy, lower haloalkyl, lower haloalkylthio, 15 halogen, hydroxy, mercapto, or RARBN-; and RA and RB are independently alkyl, hydrogen, halogen, haloalkyl, or heterocycle. 29. The compound according to claim 28 that is l-Thia2ol-2-yl-l,2,3,6-tetrahydro-pyridine-4-carboxylic acid (4- 20 trifluoromethanesulfonyl-phenyl)-amide; or l-Thiazol-2-yl-l,2,3)6-tetraliydro-pyridine-4-carboxylicacid (4-terM>utyl-phenyI)-amide. 30. A compound of formula (VII) 31. 109 WO 2005/007642 PCT/US2004/021836 \^ o XcT x7 (vn) wherein Xi isNorCRi; 5 X5 is N or CR5; Xs is a bond or CR$; X7 is N or CR7; X8 is N or CRs; XgisNorCRg; 10 R1s R5, and R9 are independently selected from the group consisting of hydrogen, alkyl. alkoxy, halogen, haloalkyl and heterocycle; R? is hydrogen, alkenyl, alkoxy, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkoxycarbonylalkyl, alkylsulfonyl, alkylthio, alkynyl, aryl, arylalkyl, aryloxy, arylthio, cyanoalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, cycloalkylthio, haloalkoxy, haloalkyl, 15 haloalkylsulfonyl, haloalkylthio, halogen, heteroaryl, heteroarylalkyl, heteroaryloxy, heteroarylthio, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, RCRDN-, (RARBN)carbonyl-, (RARBN)sulfonyI-; orRAS(0)2-; R6 and R8 are independently hydrogen, lower alkenyl, lower alkoxy, lower alkyl, lower alkylthio, lower alkynyl, lower haloalkoxy, lower haloalkyl, lower haloalkylthio, halogen, 20 hydroxy, mercapto, or RAR@N-; RA and RB are independently alkyl, hydrogen, haloalkyl, or heterocycle; and Re and RD are independently hydrogen, alkenyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkynyl, or (NRARB)carbonyl. 25 31. A compound according to claim 30, wherein XjisCR,; X5 is CR5; 110 WO 2005/007642 PCT/US2004/02J836 X6 is CR«; X7 is CR7; X8 is CRg; X9isNorCR9; 5 R7 and R8 are independently selected from the group consisting of hydrogen, alkyl, and halogen. 32. A compound according to claim 31 that is 3,-ChJoro-3s6-dihydro-2//-[l,2']bipyridinyl4-carboxylicacid(5-fluoro-pyridin-2-yl)-10 amide; 3,-CWorO-3,6-dihydro-2i/-[l?2']bipyridinyl-4-carboxylicacid(5-chloro-pyridin-2-yl)-amide; 3,-CWoro-3s6-dihydro-2H-[l,2']bipyridinyl-4-carboxylicacid(5-bromo-pyridin-2- yl)-amide; 15 3?-Chloro-3,6-dihydro-2//-[l;2']bipyridinyl-4-carboxylic acid (5-iodo-pyridin-2-yl)- amide; or 3'-Trifluoromethyl-3,6-dihydro-2/f-[l.-2']bipyridinyl-4-carboxylicacid (5-iodo-pyridin-2~yl)-amide. 20 33. The compound according to claim 30, wherein X, isCRj; X5 is CR5; X6 is CR^; X7 is CR7; 25 X8isN; X9 is CR9; Rs, R& R9 and Rj, axe independently selected from the group consisting of hydrogen, alkyl, haloalkyl. and halogen: R7 is hydrogen, alkenyl. alkoxy, alkoxycarbonyl, alkoxysulfonyl, alkyl, alkylcarbonyl, 30 alkoxycarbonylalkyl, alkylsulfonyl, alkylthio, alkynyl, aryl, arylalkyl, aryloxy, arylthio, cyanoalkyl, cycloalkyl. cycloalkylalkyl, cycloalkyloxy, cycloalkylthio, haloalkoxy, haloalkyl, haloalkylsulfonyl, haloalkylthio, halogen, heteroaryl, heteroarylalkyl, heteroaryloxy. 111 WO 2005/007642 PCT7US2004/02183(1 heteroarylthio, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, RCRDN-, (RARBN)carbonyl-, (RARBN)suifonyl-; 0r RAS(0)2S RA and RB are independently alkyl, hydrogen, haloalkyl, or heterocycle; and Re and RD are independently hydrogen, alkenyl, alkoxycarbonyl, alkyl, alkylcarbonyl, 5 alkynyl, or (NRARB)carbonyl-. 34. A compound according to claim 33 that is 3*-Chloro-3,6-diliydro-2//'-[l,2,]bipyridinyl-4-carboxylie acid (6-trifluoromethyl- pyridin-3-yl)-amide; 10 3'-Chloro-3>6-dihydro-2//-[l,2']bipyridinyl-4-carboxyh'c acid (6-chloro-pyridin-3- yl)-amide; 3'-ChloroO,6-dihydro-2/^[l,2']bipyridinyN4-carboxylicacid(3s4,5,6-terrahydro-2^-[l,2']bipYridinyl-5s-yI)-amide; 3' -ChIoro-3,6-dihydro-2.tf-[ 1,2 ']bipyridinyl-4-carboxylic acid (6-azepan-1 -yl-pyridin-15 3-yl)-amide; or 3'-Trifluoromethyl-3,6-dihydro-2i/-[l,2']bipyridinyl-4-carboxylicacid(6-trifluoromethyI-pyridin-3-yl)-amide. 35. The compound according to claim 30, wherein 20 wherein XiisCRi; X5 is CR5; X8 is a bond; X7isN; 25 X8 is N; X9 is CR9; Ri, R9 and R5) are independently selected from the group consisting of hydrogen, alkyl., haloalkyl, and halogen. 30 36. The compound according to claim 35 that is 3'-Chloro-3^dmydro-2^-[l,2']bipyridinyl-4-carboxylicacid(l-/e/t-butyl-lH-pyrazol-4-yl)-amide. 112 WO 2005/007642 PCT/US2004/021836 37. A compound according to claim 30 X, isN; X5 is CR5; 5 X6 is CR$; X7 is CR7; XgisN; X9 is CR9; R$5 R7j R9 and Rs, are independently selected from the group consisting of hydrogen, alkyl, 10 haloalkyl, and halogen. 38. A compound according to claim 37 that is l-pyrimidin-2-yl~l,2,3.6-tetrahydro-pyridine-4-carboxylicacid (6-trifluoromethyl- pyridin-3-yl)-amide 15 40. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I-VII) or a pharmaceutically acceptable salt thereof. 41. A method of treating pain in a mammal, comprising administering a therapeutically 20 effective amount of a compound of formula (I-VII) or a pharmaceutically acceptable salt thereof. 42. A pharmaceutical composition comprising a therapeutically effective amount of 3'- (trifluoromethyl)-N-{4-[(trifluoromethyl)sulfonyl]phenyl}-3?6-dihydro-2H-l,2'-bipyridine-4- 25 carboxamide or a pharmaceutically acceptable salt thereof. 43. A method of treating pain in a mammal, comprising administering a therapeutically effective amount of 3,-(trifluoromethyl)-N-{4-[(trifluoromethyl)suIfonyl]phenyl}-3,6- dihydro-2H-l,2'-bipyridine-4-carboxamide or a pharmaceutically acceptable salt thereof. 30 113