Isoxazolidine as a RIPK1 inhibitor and its use
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- GENZYME CORP
- Filing Date
- 2024-05-07
- Publication Date
- 2026-06-25
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Figure 2026520851000001_ABST
Abstract
Claims
1. Equation (I) 【Chemistry 1】 (In the formula, R1 represents a phenyl or monocyclic heteroaryl molecule that is optionally substituted by one, two, or three R3 molecules. R2 represents an aryl or heteroaryl that is optionally substituted by one, two, or three R6s. Each R3 independently controls halogen, cyanoacrylate, (C １ ~C ４ ) alkyl group or (C １ ~C ４ ) Selected from alkoxy groups, R4 and R5 are independently selected from halogen, (C １ ~C ４ )-alkyl group, (C １ ~C ４ )-alkoxy group, or R4 and R5 together form a (C １ ~C ４ )-alkylene bridge, m and s are independently 0 or 1. p, q, r, and t are independently either 0 or 1. Each R6 independently contains halogen, cyano, -OH, and -NH ２ Group, (C １ ~C ４ ) Alkyl alkyl group, -CF ３ , -C(O)NH ２ , -C(O)NH-(C １ ~C ４ ) alkyl group, -C(O)OH, -C(O)O-(C １ ~C ４ ) alkyl group, -SO ２ NH ２ , (C １ ~C ４ ) Alkoxy group, -O-(C １ ~C ４ ) Alkylene-(C ３ ~C ６ ) Cycloalkyl group, -O-(C ３ ~C ６ ) Cycloalkyl group, -O-(C ３ ~C ６ ) Heterocycloalkyl groups, (C ３ ~C ６ ) Selected from heterocycloalkyl groups, heteroaryl groups and oxo, and the above (C １ ~C ４ ) alkyl group, (C １ ~C ４ ) Alkoxy group, -O-(C ３ ~C ６ ) Cycloalkyl groups, (C １ ~C ４ ) alkyl group, (C ３ ~C ６ The heterocycloalkyl or heteroaryl group is optionally substituted with 1, 2, 3, or 4 R7 groups. Each R7 independently contains halogen, oxo, -OH, (C １ ~C ４ ) alkyl group or (C １ ~C ４ (It is an alkoxy group.) The compound or its pharmaceutically acceptable salt, solvate, or stereoisomer.
2. R1 represents a phenyl or a 5- or 6-membered monocyclic heteroaryl which is optionally substituted by 1, 2, or 3 R3s. R2 represents a phenyl, a 5 or 6-membered monocyclic heteroaryl, or a 9 or 10-membered bicyclic heteroaryl, which is optionally substituted by 1, 2, or 3 R6s. Each R3 independently controls halogen, cyanoacrylate, (C １ ~C ４ ) alkyl groups and (C １ ~C ４ ) Selected from alkoxy groups, R4 and R5 are (C １ ~C ４ ) Together form alkylene crosslinks, m and s are independently 0 or 1. p, q, r, and t are independently either 0 or 1. Each R6 independently controls halogen, cyanoacrylate, and -NH3. ２ group, -OH, (C １ ~C ４ ) Alkyl alkyl group, -C(O)NH ２ , -C(O)NH-(C １ ~C ４ ) alkyl group, (C １ ~C ４ ) Alkoxy group, -O-(C １ ~C ４ ) Alkylene-(C ３ ~C ６ ) Cycloalkyl group, -O-(C ３ ~C ６ ) Cycloalkyl group, -O-(C ３ ~C ６ ) Selected from heterocycloalkyl groups, 4 or 5-membered heterocycloalkyl groups, 5 or 6-membered heteroaryl groups, and oxo groups, the (C １ ~C ４ ) alkyl group, (C １ ~C ４ ) Alkoxy group, -O-(C ３ ~C ６ ) Cycloalkyl groups, heterocycloalkyl groups, and heteroaryl groups are optionally substituted with one or two R7 groups. Each R7 independently controls -OH, (C １ ~C ４ ) alkyl group or (C １ ~C ４ A compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, which is an alkoxy group.
3. The following formula (Ig): 【Chemistry 2】 (wherein R1, R2, R4, R5, r, q, p, t, m, and s are as defined in claim 1 or 2.) A compound of formula (I) according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, having the above.
4. The following equation (Ia): 【Transformation 3】 (wherein R1, R2, R4, R5, m and s are as defined in claim 1 or 2) A compound of formula (I) according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, having the above.
5. R1 is a phenyl molecule that is optionally substituted with one or two R3 molecules. R2 is a nine-membered bicyclic heteroaryl, particularly benzimidazolyl, which is optionally substituted by one or two R6s. Each R3 can be independently a halogen, cyanoacrylate, or (C １ ~C ４ ) Selected from alkyl groups, m and s are 0, Each R6 is a halogen, particularly fluorine, in the compound of formula (Ia) according to claim 4 or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.
6. The following equation (If): 【Chemistry 4】 (wherein R1, R2, R4, R5, m and s are as defined in claim 4 or 5) A compound of formula (Ia) according to claim 4 or 5, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, having the above.
7. The following formula (Ib): 【Transformation 5】 (wherein R1, R2, R4, R5, m and s are as defined in claim 1 or 2) A compound of formula (I) according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, having the above.
8. The following formula (Ic): 【Transformation 6】 (wherein R1, R2, R4, R5, m and s are as defined in claim 1 or 2) A compound of formula (I) according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, having the above.
9. R1 is a phenyl or a six-membered monocyclic heteroaryl which is optionally substituted by one or two R3 molecules, and in particular, R1 is a phenyl, pyrazinyl, pyridinyl, thiazolyl, oxazolyl, or pyrimidinyl which is optionally substituted by one or two R3 molecules. R2 is a 5 or 6-membered monocyclic heteroaryl or a 9-membered bicyclic heteroaryl that is optionally substituted by one or two R6s, and in particular, R2 is imidazopyridazinyl, indazolyl, pyrazolyl, pyridinyl, pyrimidinyl, triazolopyridazinyl, triazolopyridinyl, pyrazolopyridinyl, imidazopyridinyl, phenyl, pyridazinyl, or thiazolyl that is optionally substituted by one or two R6s. Each R3 independently controls halogen, cyanoacrylate, (C １ ~C ４ ) alkyl group or (C １ ~C ４ ) Selected from alkoxy groups, in particular, each R3 is independently selected from fluorine, cyano, methoxy, or methyl. m and s are either 0, or m is 0 and s is 1, and R4 is a methyl group. Each R6 is independently halogen, cyano, -NH ２ group, (C １ ~C ４ ) alkyl group, (C １ ~C ４ ) alkoxy group, -CF ３ , 1, 2, 3 or 4 R7 optionally substituted (C ３ ~C ６ ) heterocycloalkyl group, and in particular, each R6 is independently selected from fluorine, cyano, methyl, methoxy or hydroxyoxetanyl, The compound of formula (Ic) according to claim 8, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein R7 is independently a halogen, oxo, -OH, methyl, or methoxy.
10. The following formula (Ie): 【Transformation 7】 (wherein R1, R2, R4, R5, m and s are as defined in claim 8 or 9) A compound of formula (Ic) according to claim 8 or 9, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, having the above.
11. The following formula (Id): 【Transformation 8】 (wherein R1, R2, R4, R5, m and s are as defined in claim 1 or 2) A compound of formula (I) according to claim 1 or 2, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, having the above.
12. The following formulas (Ib), (Ic), and especially formula (Ie) or (Id): 【Chemistry 9】 (wherein R1, R2, R4, R5, m and s are as defined in claim 1 or 2) A compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, having the above, especially, Formula (Ib) according to claim 7, Formula (Ic) according to claim 8 or 9, more specifically formula (Ie) according to claim 10, or Formula (Id) according to claim 11 A compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, having the above, More specifically, Formula (Ib) according to claim 7, Formula (Ic) according to claim 8 or 9, more specifically, formula (Ie) according to claim 10 A compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, having the above.
13. base 【Chemistry 10】 When it is cyclobutyl optionally substituted, R4 and R5 are independently halogen, (C １ -C ４ ), an alkyl group or (C １ -C ４ ), an alkoxy group, and the compound of formula (I) according to claim 1.
14. (1) trans-3-[(3S)-2-[4-[(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-7-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (2) trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-pyrrolo[3,2-b]pyridine-6-carbonitride, (3) trans-1-((4-((S)-3-(5-fluoropyridine-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-pyrrolo[3,2-b]pyridine-6-carbonitride, (4)trans-1-((4-((S)-3-(5-fluoropyridine-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-methyl-1H-imidazole-5-carbonitrile, (5)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carbonitrile, (6)trans-1-((4-((S)-3-(5-fluoropyridine-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carbonitrile, (7) trans-3-((S)-2-(4-((1H-benzo[d]imidazole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)-5-fluorobenzonitrile, (8) trans-(4-((1H-benzo[d]imidazole-1-yl)methyl)cyclohexyl)((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)methanone, (9) trans-(4-((1H-benzo[d]imidazole-1-yl)methyl)cyclohexyl)((S)-3-(5-fluoropyridine-3-yl)isoxazolidine-2-yl)methanone, (10)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-6-fluoro-1H-benzo[d]imidazole-5-carbonitrile, (11)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-6-fluoro-1H-benzo[d]imidazole-5-carbonitrile, (12)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-1H-benzo[d]imidazole-6-carbonitrile, (13)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-1H-benzo[d]imidazole-6-carbonitrile, (14)trans-3-((S)-2-(4-((1H-pyrrolo[3,2-b]pyridine-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)-5-fluorobenzonitrile, (15)trans-3-((S)-2-(4-((1H-pyrrolo[3,2-c]pyridine-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)-5-fluorobenzonitrile, (16)trans-3-((S)-2-(4-((1H-pyrrolo[2,3-c]pyridine-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)-5-fluorobenzonitrile, (17)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile, (18)trans-3-fluoro-5-((S)-2-(4-((2-oxobenzo[d]oxazole-3(2H)-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)benzonitrile, (19)trans-3-((S)-2-(4-((6-chloro-1H-pyrrolo[3,2-b]pyridine-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)-5-fluorobenzonitrile, (20)trans-3-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)benzo[d]oxazole-2(3H)-one, (21)trans-(4-((6-chloro-1H-pyrrolo[3,2-b]pyridine-1-yl)methyl)cyclohexyl)((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)methanone, (22)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-1H-indole-6-carbonitride, (23)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-1H-indole-6-carbonitride, (24)trans-2-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-2H-pyrazolo[4,3-b]pyridine-6-carbonitrile, (25)trans-2-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-2H-pyrazolo[4,3-b]pyridine-6-carbonitrile, (26)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile, (27)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile, (28)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-indazole-6-carbonitrile, (29)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-indazole-6-carbonitrile, (30)trans-2-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-2H-indazole-6-carbonitrile, (31)trans-2-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-2H-indazole-6-carbonitrile, (32)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-1H-indazole-6-carbonitrile, (33)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-1H-indazole-6-carbonitrile, (34)trans-2-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-2H-indazole-6-carbonitrile, (35)trans-2-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-2H-indazole-6-carbonitrile, (36)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-1H-benzo[d]imidazole-6-carbonitrile, (37)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-1H-benzo[d]imidazole-6-carbonitrile, (38)trans-4-fluoro-1-((4-((S)-3-(5-methylfuran-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-6-carbonitrile, (39)trans-5-fluoro-1-((4-((S)-3-(5-methylfuran-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-6-carbonitrile, (40)trans-6-fluoro-1-((4-((S)-3-(5-methylfuran-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carbonitrile, (41)trans-2-((4-((S)-3-(5-methylfuran-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-2H-indazole-6-carbonitrile, (42)trans-4-fluoro-2-((4-((S)-3-(5-methylfuran-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-2H-indazole-6-carbonitrile, (43)trans-1-((4-((S)-3-(5-methylfuran-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-indazole-6-carbonitrile, (44)trans-4-fluoro-1-((4-((S)-3-(5-methylfuran-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-indazole-6-carbonitrile, (45)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-1H-indole-6-carbonitride, (46)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-1H-indole-6-carbonitride, (47)trans-4-fluoro-1-((4-((S)-3-(5-methylfuran-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-indole-6-carbonitrile, (48)trans-3-fluoro-5-((S)-2-(4-((5-fluoro-1H-benzo[d]imidazole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)benzonitrile, (49)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(4-((5-fluoro-1H-benzo[d]imidazole-1-yl)methyl)cyclohexyl)methanone, (50)trans-3-fluoro-5-((S)-2-(4-((5-fluoro-2-methyl-1H-benzo[d]imidazole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)benzonitrile, (51)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(4-((5-fluoro-2-methyl-1H-benzo[d]imidazole-1-yl)methyl)cyclohexyl)methanone, (52)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-indazole-5-carbonitrile, (53)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-indazole-5-carbonitrile, (54)trans-3-fluoro-5-((S)-2-(4-((5-fluoro-1H-indazole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)benzonitrile, (55)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(4-((5-fluoro-1H-indazole-1-yl)methyl)cyclohexyl)methanone, (56)trans-3-fluoro-5-((S)-2-(4-((5-fluoro-2H-indazole-2-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)benzonitrile, (57)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(4-((5-fluoro-2H-indazole-2-yl)methyl)cyclohexyl)methanone, (58)trans-2-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-2H-indazole-5-carbonitrile, (59)trans-2-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-2H-indazole-5-carbonitrile, (60)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(4-((3-methyl-1H-indazole-1-yl)methyl)cyclohexyl)methanone, (61)trans-3-fluoro-5-((S)-2-(4-((3-methyl-1H-indazole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)benzonitrile, (62)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(4-((3-methyl-2H-indazole-2-yl)methyl)cyclohexyl)methanone, (63)trans-3-fluoro-5-((S)-2-(4-((3-methyl-2H-indazole-2-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)benzonitrile, (64)trans-1-((4-((S)-3-(5-cyanopyridine-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-1H-benzo[d]imidazole-6-carbonitrile, (65)trans-1-((4-((S)-3-(5-cyanopyridine-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-6-fluoro-1H-benzo[d]imidazole-5-carbonitrile, (66)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-6-fluoro-1H-indazole-5-carbonitrile, (67)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-6-fluoro-1H-indazole-5-carbonitrile, (68)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-6-fluoro-3-methyl-1H-indazole-5-carbonitrile, (69)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-6-fluoro-3-methyl-1H-indazole-5-carbonitrile, (70)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-1H-benzo[d]imidazole-6-carboxamide, (71)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-1H-benzo[d]imidazole-6-carboxamide, (72)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-indazole-5-carboxamide, (73)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-indazole-5-carboxamide, (74)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-6-fluoro-1H-benzo[d]imidazole-5-carboxamide, (75)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-6-fluoro-1H-benzo[d]imidazole-5-carboxamide, (76)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-1H-indole-6-carboxamide, (77)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-1H-indole-6-carboxamide, (78)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-pyrazolo[4,3-b]pyridine-6-carboxamide, (79)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-pyrazolo[4,3-b]pyridine-6-carboxamide, (80)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-1H-benzo[d]imidazole-6-carboxamide, (81)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-1H-benzo[d]imidazole-6-carboxamide, (82)trans-3-((S)-2-(4-((4,5-dimethyl-1H-imidazole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)-5-fluorobenzonitrile, (83)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(4-((4,5-dimethyl-1H-imidazole-1-yl)methyl)cyclohexyl)methanone, (84)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-3-methyl-1H-indazole-6-carbonitrile, (85)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-3-methyl-1H-indazole-6-carbonitrile, (86)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-1H-indazole-6-carbonitrile, (87)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-fluoro-1H-indazole-6-carbonitrile, (88)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-methyl-1H-imidazole-5-carbonitrile, (89)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-methyl-1H-imidazole-5-carbonitrile, (90)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-methyl-1H-imidazole-4-carbonitrile, (91)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-5-methyl-1H-imidazole-4-carbonitrile, (92)trans-(4-((5-fluoro-1H-benzo[d]imidazole-1-yl)methyl)cyclohexyl)((S)-3-(pyrazine-2-yl)isoxazolidine-2-yl)methanone, (93)trans-3-fluoro-5-((S)-2-(4-((6-fluoro-1H-pyrrolo[3,2-b]pyridine-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)benzonitrile, (94)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(4-((6-fluoro-1H-pyrrolo[3,2-b]pyridine-1-yl)methyl)cyclohexyl)methanone, (95)trans-3-fluoro-5-((S)-2-(4-((5-fluoro-1H-indole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)benzonitrile, (96)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(4-((5-fluoro-1H-indole-1-yl)methyl)cyclohexyl)methanone, (97)trans-6-fluoro-1-((4-((S)-3-(pyrazine-2-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-5-carbonitrile, (98)trans-5-fluoro-1-((4-((S)-3-(pyrazine-2-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-benzo[d]imidazole-6-carbonitrile, (99)trans-1-[[4-[(3S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]pyrrolo[3,2-b]pyridine-5-carbonitride, (100)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-3-methyl-1H-indazole-6-carbonitrile, (101)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-3-methyl-1H-indazole-6-carbonitrile, (102)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-3-methyl-1H-indazole-6-carboxamide, (103)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-3-methyl-1H-indazole-6-carboxamide, (104)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-indole-6-carboxamide, (105)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-indole-6-carboxamide, (106)trans-5-((S)-2-(4-((6-fluoro-1H-benzo[d]imidazole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)nicotinonitrile, (107)trans-5-((S)-2-(4-((5-fluoro-1H-benzo[d]imidazole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)nicotinonitrile, (108)trans-1-((4-((S)-3-(5-cyanopyridine-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile, (109)trans-5-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-2-methylbenzonitrile, (110)trans-1-((4-((S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-3-methyl-1H-indole-6-carboxamide, (111)trans-1-((4-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-3-methyl-1H-indole-6-carboxamide, (112)trans-3-fluoro-5-((S)-2-(4-((6-fluoro-1H-benzo[d]imidazole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)benzonitrile, (113)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(4-((6-fluoro-1H-benzo[d]imidazole-1-yl)methyl)cyclohexyl)methanone, (114)trans-(3-((5-fluoro-1H-benzo[d]imidazole-1-yl)methyl)cyclobutyl)((S)-3-(p-tolyl)isoxazolidine-2-yl)methanone, (115)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(3-((5-fluoro-1H-benzo[d]imidazole-1-yl)methyl)cyclobutyl)methanone, (116)trans-3-fluoro-5-((S)-2-(3-((5-fluoro-1H-benzo[d]imidazole-1-yl)methyl)cyclobutan-1-carbonyl)isoxazolidine-3-yl)benzonitrile, (117)trans-(4-((3,5-dimethyl-1H-pyrazole-1-yl)methyl)cyclohexyl)((S)-3-(p-tolyl)isoxazolidine-2-yl)methanone, (118)trans-((S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl)(4-((3,5-dimethyl-1H-pyrazole-1-yl)methyl)cyclohexyl)methanone, (119)trans-3-((S)-2-(4-((3,5-dimethyl-1H-pyrazole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)-5-fluorobenzonitrile, (120)trans-3-fluoro-5-[(3S)-2-[4-[(5-methoxypyrrolo[3,2-b]pyridine-1-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (121)trans-2-((4-((S)-3-(5-cyanopyridine-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-2H-pyrazolo[3,4-b]pyridine-5-carbonitrile, (122)trans-1-[[4-[(3S)-3-(5-cyano-3-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-6-oxopyridine-3-carbonitrile, (123)trans-5-((S)-2-(4-((6-fluoro-1H-pyrrolo[3,2-b]pyridine-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)nicotinonitrile, (124)trans-3-[(3S)-2-[4-[[6-(3,5-dimethylpyrazole-1-yl)pyrimidine-4-yl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]-5-fluorobenzonitrile, (125)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[[6-(3,5-dimethylpyrazole-1-yl)pyrimidine-4-yl]methyl]cyclohexyl]methanone, (126)trans-5-((S)-2-(4-((5-fluoro-1H-indazole-1-yl)methyl)cyclohexane-1-carbonyl)isoxazolidine-3-yl)nicotinonitrile, (127)trans-2-((4-((S)-3-(5-cyanopyridine-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-2H-indazole-6-carbonitrile, (128)trans-3-fluoro-5-[(3S)-2-[4-[(6-methoxypyrrolo[3,2-b]pyridine-1-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (129)trans-3-fluoro-5-[(3S)-2-[4-[(6-hydroxypyrrolo[3,2-b]pyridine-1-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (130)trans-1-((4-((S)-3-(5-cyanopyridine-3-yl)isoxazolidine-2-carbonyl)cyclohexyl)methyl)-4-fluoro-1H-indole-6-carbonitride, (131)trans-2-methyl-5-[[4-[(3S)-3-(p-tolyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]benzamide, (132)trans-5-[[4-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-2-methyl-benzamide, (133)trans-5-[[4-[(3S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-2-methyl-benzamide, (134)trans-1-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]pyrrolo[3,2-b]pyridine-6-carbonitride, (135)trans-3-fluoro-5-[(3S)-2-[4-[[6-(2-methylimidazole-1-yl)pyrimidine-4-yl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (136)trans-[4-[[6-(2-methylimidazole-1-yl)pyrimidine-4-yl]methyl]cyclohexyl]-[(3S)-3-(p-tolyl)isoxazolidine-2-yl]methanone, (137)trans-1-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]pyrazolo[4,3-b]pyridine-6-carbonitride, (138)trans-2-methyl-5-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]benzamide, (139)trans-2-methyl-5-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]benzonitrile, (140)trans-5-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]pyridine-3-carbonil, (141)trans-5-[[4-[(3S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]pyridine-3-carbonil, (142)trans-3-fluoro-5-[(3S)-2-[4-([1,2,4]triazolo[1,5-a]pyridine-6-ylmethyl)cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (143)trans-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]-[4-([1,2,4]triazolo[1,5-a]pyridine-6-ylmethyl)cyclohexyl]methanone, (144)trans-3-fluoro-5-[(3S)-2-[4-[(3-oxoisoindolin-5-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (145)trans-6-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]isoindorin-1-one, (146)trans-3-fluoro-5-[(3S)-2-[4-[[6-(oxetane-3-yloxy)pyrrolo[3,2-b]pyridine-1-yl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (147)trans-[4-[(5-fluoro-3-pyridyl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (148)trans-3-fluoro-5-[(3S)-2-[4-[(5-fluoro-3-pyridyl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (149)trans-3-fluoro-5-[(3S)-2-[4-[[6-(2-methoxyethoxy)pyrrolo[3,2-b]pyridine-1-yl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (150)trans-3-fluoro-5-[(3S)-2-[4-[(1-methylpyrazole-4-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (151)trans-[4-[(1-methylpyrazole-4-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (152)trans-3-[(3S)-2-[4-[[6-(cyclopropylmethoxy)pyrrolo[3,2-b]pyridine-1-yl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]-5-fluorobenzonitrile, (153)trans-3-fluoro-5-[(3S)-2-[4-[[6-(2-hydroxyethoxy)pyrrolo[3,2-b]pyridine-1-yl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (154)trans-6-[[4-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]isoindorin-1-one, (155)trans-6-[[4-[(3S)-3-(5-fluoro-3-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]isoindorin-1-one, (156)trans-6-[[4-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]isoindorin-1-one, (157)trans-6-[[4-[(3S)-3-(6-methyl-3-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]isoindorin-1-one, (158)trans-5-[[4-[(3S)-3-(5-cyano-3-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-2-methyl-benzamide, (159)trans-2-methyl-5-[[4-[(3S)-3-(2-methylthiazole-4-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]benzamide, (160)trans-3-fluoro-5-[[4-[(3S)-3-(5-fluoro-3-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-N-methyl-benzamide, (161)trans-3-[[4-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-5-fluoro-N-methyl-benzamide, (162)trans-3-fluoro-N-methyl-5-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]benzamide, (163)trans-3-[[4-[(3S)-3-(5-cyano-3-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-5-fluoro-N-methyl-benzamide, (164)trans-3-[[4-[(3S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-5-fluoro-N-methyl-benzamide, (165)trans-3-fluoro-5-[[4-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-N-methyl-benzamide, (166)trans-5-[[4-[(3S)-3-(6-methoxypyrazine-2-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-2-methyl-benzamide, (167)trans-3-fluoro-5-[(3S)-2-[4-[(3-methylimidazole-4-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (168)trans-5-[(3S)-2-[4-[(3-methylimidazole-4-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]pyridine-3-carbonitrile, (169)trans-3-fluoro-5-[(3S)-2-[4-[[4-(3-hydroxyoxetan-3-yl)phenyl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (170)trans-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-yl]-[4-[[4-(3-hydroxyoxetan-3-yl)phenyl]methyl]cyclohexyl]methanone, (171)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[[4-(3-hydroxyoxetan-3-yl)phenyl]methyl]cyclohexyl]methanone, (172)trans-4-fluoro-3-[[4-[(3S)-3-(5-fluoro-3-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-N-methyl-benzamide, (173)trans-4-fluoro-3-[[4-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-N-methyl-benzamide, (174)trans-3-[[4-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-4-fluoro-N-methyl-benzamide, (175)trans-4-fluoro-N-methyl-3-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]benzamide, (176)trans-3-[[4-[(3S)-3-(5-cyano-3-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-4-fluoro-N-methyl-benzamide, (177)trans-3-[[4-[(3S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-4-fluoro-N-methyl-benzamide, (178)trans-[4-[(5-fluoro-2-methyl-3-pyridyl)methyl]cyclohexyl]-[(3S)-3-(5-fluoro-3-pyridyl)isoxazolidine-2-yl]methanone, (179)trans-[4-[(5-fluoro-2-methyl-3-pyridyl)methyl]cyclohexyl]-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-yl]methanone, (180)trans-[4-[(5-fluoro-2-methyl-3-pyridyl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (181)trans-3-fluoro-5-[(3S)-2-[4-[(5-fluoro-2-methyl-3-pyridyl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (182)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(5-fluoro-2-methyl-3-pyridyl)methyl]cyclohexyl]methanone, (183)trans-5-[(3S)-2-[4-[[4-(3-hydroxyoxetan-3-yl)phenyl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]pyridine-3-carbonitrile, (184)trans-3-fluoro-5-[(3S)-2-[4-[[6-(1-methylcyclopropoxy)pyrrolo[3,2-b]pyridine-1-yl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (185)trans-1-[[4-[(3S)-3-(6-methoxypyrazine-2-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]pyrrolo[3,2-b]pyridine-6-carbonitrile, (186)trans-1-[[4-[(3S)-3-(6-methoxypyrazine-2-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]pyrazolo[4,3-b]pyridine-6-carbonitride, (187)trans-1-[[4-[(3S)-3-(2-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]pyrazolo[4,3-b]pyridine-6-carbonitride, (188)trans-1-[[4-[(3S)-3-(2-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]pyrrolo[3,2-b]pyridin-6-carbonitride, (189)trans-2-[[4-[(3S)-3-(6-methoxypyrazine-2-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carbonitrile, (190)trans-1-[[4-[(3S)-3-(6-methoxypyrazine-2-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carbonitrile, (191)trans-2-fluoro-5-[[4-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]benzamide, (192)trans-5-[[4-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-2-fluorobenzamide, (193)trans-2-fluoro-5-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]benzamide, (194)trans-5-[[4-[(3S)-3-(5-cyano-3-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-2-fluorobenzamide, (195)trans-5-[[4-[(3S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-2-fluorobenzamide, (196)trans-2-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carbonil, (197)trans-5-[(3S)-2-[4-[(5-fluoro-2-methyl-3-pyridyl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]pyridine-3-carbonitrile, (198)trans-1-[[4-[(3S)-3-(2-methylthiazole-4-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]pyrrolo[3,2-b]pyridine-6-carbonitrile, (199)trans-1-[[4-[(3S)-3-(2-methylthiazole-4-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]pyrazolo[4,3-b]pyridine-6-carbonitride, (200)trans-1-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carbonitrile, (201)trans-1-[[4-[(3S)-3-(6-methoxypyrazine-2-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carboxamide, (202)trans-1-[[4-[(3S)-3-(2-methylthiazole-4-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-5-carbonitride, (203)trans-2-[[4-[(3S)-3-(2-methylthiazole-4-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carbonitrile, (204)trans-1-[[4-[(3S)-3-(2-methylthiazole-4-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carbonitrile, (205)trans-[4-[(8-fluoro-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (206)trans-3-fluoro-5-[(3S)-2-[4-[(8-fluoro-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (207)trans-[4-[[3-fluoro-5-(2-methylimidazole-1-yl)phenyl]methyl]cyclohexyl]-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-yl]methanone, (208)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[[3-fluoro-5-(2-methylimidazole-1-yl)phenyl]methyl]cyclohexyl]methanone, (209)trans-[4-[[3-fluoro-5-(2-methylimidazole-1-yl)phenyl]methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (210)trans-5-[(3S)-2-[4-[[3-fluoro-5-(2-methylimidazole-1-yl)phenyl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]pyridine-3-carbonitrile, (211)trans-[4-[[3-fluoro-5-(2-methylpyrazole-3-yl)phenyl]methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (212)trans-4-fluoro-6-[[4-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]isoindorin-1-one, (213)trans-4-fluoro-6-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]isoindorin-1-one, (214)trans-3-fluoro-5-[(3S)-2-[4-[[3-fluoro-5-(2-methylpyrazole-3-yl)phenyl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (215)trans-1-[[4-[(3S)-3-(2-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carbonitride, (216)trans-3-fluoro-5-[(3S)-2-[4-[[3-fluoro-5-(2-methylimidazole-1-yl)phenyl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (217)trans-1-[[4-[(3S)-3-(6-methoxypyrazine-2-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-5-carbonitride, (218)trans-1-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-5-carbonitride, (219)trans-3-fluoro-5-[(3S)-2-[4-[(7-fluoro-3-oxo-isoindolin-5-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (220)trans-[4-[[3-fluoro-5-(2-methylimidazole-1-yl)phenyl]methyl]cyclohexyl]-[(3S)-3-(5-fluoro-3-pyridyl)isoxazolidine-2-yl]methanone, (221)trans-3-fluoro-5-[(3S)-2-[4-[(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (222)trans-[4-[(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (223)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (224)trans-3-fluoro-5-[(3S)-2-[4-[(3-methyl-[1,2,4]triazolo[4,3-a]pyridine-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (225)trans-3-fluoro-5-[(3S)-2-[4-[(2-methylimidazo[1,2-a]pyridine-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (226)trans-[4-[(2-methylimidazo[1,2-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (227)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(2-methylimidazo[1,2-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (228)trans-2-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carboxamide, (229)trans-1-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carboxamide, (230)trans-1-[[4-[(3S)-3-(2-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carboxamide, (231)trans-1-[[4-[(3S)-3-(4-cyano-2-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carboxamide, (232)trans-2-[[4-[(3S)-3-(4-cyano-2-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carboxamide, (233)trans-2-[[4-[(3S)-3-(2-methylthiazole-4-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carboxamide, (234)trans-1-[[4-[(3S)-3-(2-methylthiazole-4-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-6-carboxamide, (235)trans-5-[(3S)-2-[4-[(1-methylpyrazole-4-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]pyridine-3-carbonitrile, (236)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(1-methylpyrazole-4-yl)methyl]cyclohexyl]methanone, (237)trans-3-fluoro-5-[(3S)-2-[4-[(2-methylpyrazole-3-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (238)trans-[4-[(2-methylpyrazole-3-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (239)trans-3-fluoro-5-[(3S)-2-[4-[(2-methylthiazole-4-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (240)trans-[4-[(2-methylthiazole-4-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (241)trans-1-[[4-[(3S)-3-(6-methoxypyrazine-2-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indole-6-carbonitride, (242)trans-2-fluoro-5-[[4-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]benzonitrile, (243)trans-2-fluoro-5-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]benzonitrile, (244)trans-5-[[4-[(3S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-2-fluorobenzonitrile, (245)trans-3-fluoro-5-[(3S)-2-[4-(pyrazine-2-ylmethyl)cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (246)trans-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]-[4-(pyrazine-2-ylmethyl)cyclohexyl]methanone, (247)trans-3-fluoro-5-[(3S)-2-[4-(pyrimidine-5-ylmethyl)cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (248)trans-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]-[4-(pyrimidine-5-ylmethyl)cyclohexyl]methanone, (249)trans-3-fluoro-5-[(3S)-2-[4-[(8-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexanecarbonyl]-1,2-oxazolidine-3-yl]benzonitrile, (250)trans-[4-[(8-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-yl-1,2-oxazolidine-2-yl]methanone, (251)trans-1-[[4-[(3S)-3-pyrazine-2-ylisoxazolidine-2-carbonyl]cyclohexyl]methyl]indole-5-carboxamide, (252)trans-1-[[4-[(3S)-3-(5-cyano-3-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indole-5-carboxamide, (253)trans-1-[[4-[(3S)-3-(6-methoxypyrazine-2-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indole-5-carboxamide, (254)trans-1-[[4-[(3S)-3-(2-methylthiazole-4-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indole-5-carboxamide, (255)trans-1-[[4-[(3S)-3-(2-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indole-5-carboxamide, (256)trans-3-fluoro-5-[(3S)-2-[4-[[3-fluoro-5-(hydroxymethyl)phenyl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (257)trans-5-[(3S)-2-[4-[[3-fluoro-5-(hydroxymethyl)phenyl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]pyridine-3-carbonitrile, (258)trans-3-fluoro-5-[(3S)-2-[4-[(1-methyltriazole-4-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (259)trans-[4-[[3-fluoro-5-(hydroxymethyl)phenyl]methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (260)trans-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-yl]-[4-[(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (261)trans-[(3S)-3-(3,4-difluorophenyl)isoxazolidine-2-yl]-[4-[(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (262)trans-5-[(3S)-2-[4-[(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]pyridine-3-carbonilicate, (263)trans-3-fluoro-5-[(3S)-2-[4-[(2-methylpyrimidine-5-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (264)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(2-methylpyrimidine-5-yl)methyl]cyclohexyl]methanone, (265)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[[3-fluoro-4-(hydroxymethyl)phenyl]methyl]cyclohexyl]methanone, (266)trans-3-fluoro-5-[(3S)-2-[4-[[3-fluoro-4-(hydroxymethyl)phenyl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (267)trans-5-[[4-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-2-methylpyridine-3-carbonil, (268)trans-5-[[4-[(3S)-3-(3-cyano-5-fluoro-phenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-2-methylpyridine-3-carbonil, (269) 5-[[4-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl]norbornan-1-yl]methyl]-2-methyl-benzamide, (270) 5-[[4-[(3S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl]norbornan-1-yl]methyl]-2-methyl-benzamide, (271) 2-methyl-5-[[4-[(3S)-3-(6-methyl-3-pyridyl)isoxazolidine-2-carbonyl]norbornan-1-yl]methyl]benzamide, (272) 2-methyl-5-[[4-[(3S)-3-(6-methyl-3-pyridyl)isoxazolidine-2-carbonyl]-1-bicyclo[2.2.2]octanyl]methyl]benzamide, (273) 5-[[4-[(3S)-3-(3,5-difluorophenyl)-1,2-oxazolidine-2-carbonyl]-1-bicyclo[2.2.2]octanyl]methyl]-2-methylbenzamide, (274) 5-[[4-[(3S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl]-1-bicyclo[2.2.2]octanyl]methyl]-2-methyl-benzamide, (275)trans-5-[[4-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-4-methylpyridine-3-carbonil, (276)trans-5-[[4-[(3S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-4-methylpyridine-3-carbonil, (277)trans-5-[[4-[(3S)-3-(3-cyano-5-fluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-6-methylpyridine-3-carbonil, (278)trans-5-[[4-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-6-methylpyridine-3-carbonil formate, (279)trans-3-fluoro-5-[(3S)-2-[4-[[3-fluoro-4-(2-hydroxyethyl)phenyl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (280)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[[3-fluoro-4-(2-hydroxyethyl)phenyl]methyl]cyclohexyl]methanone, (281)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(8-fluoro-2-methyl-imidazo[1,2-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (282)trans-3-fluoro-5-[(3S)-2-[4-[[3-fluoro-5-(2-hydroxyethyl)phenyl]methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (283)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[[3-fluoro-5-(2-hydroxyethyl)phenyl]methyl]cyclohexyl]methanone, (284)trans-3-fluoro-5-[(3S)-2-[4-[(8-fluoro-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (285)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(8-fluoro-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (286)trans-5-[[4-[(3S)-3-(3-cyano-5-fluoro-4-methyl-phenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-2-methylpyridine-3-carbonitrile, (287)trans-5-[[4-[(3S)-3-(3-cyano-5-fluoro-4-methyl-phenyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]-4-methylpyridine-3-carbonil, (288)trans-3-[(3S)-2-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]-5-fluorobenzonitrile, (289)trans-4-fluoro-3-[(3S)-2-[4-[(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (290)trans-3-[(3S)-2-[4-[(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]-5-fluorobenzonitrile, (291)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)methyl]cyclohexyl]methanone, (292)trans-3-[(3S)-2-[4-[(2,7-dimethylimidazo[1,2-b]pyridazin-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]-5-fluorobenzonitrile, (293)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(2,7-dimethylimidazo[1,2-b]pyridazin-6-yl)methyl]cyclohexyl]methanone, (294)trans-3-fluoro-5-[(3S)-2-[4-[(1-methylindazole-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (295)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(1-methylindazole-6-yl)methyl]cyclohexyl]methanone, (296)trans-3-fluoro-5-[(3S)-2-[4-[(1-methylpyrazolo[4,3-b]pyridine-6-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (297)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(1-methylpyrazolo[4,3-b]pyridine-6-yl)methyl]cyclohexyl]methanone, (298) 6-fluoro-1-[[trans-4-[(3S)-3-(6-methyl-3-pyridyl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]indazole-5-carbonil, (299)trans-2-fluoro-5-[[4-[(3S)-3-(6-methylpyrazine-2-yl)isoxazolidine-2-carbonyl]cyclohexyl]methyl]benzamide, (300)trans-3-[(3S)-2-[4-[(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridine-6-yl)methyl]cyclohexanecarbonyl]-1,2-oxazolidine-3-yl]-5-fluorobenzonitrile, (301)trans-[4-[(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-yl-1,2-oxazolidine-2-yl]methanone, (302)trans-3-fluoro-5-[(3S)-2-[4-[(6-methylpyridazin-4-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (303)trans-3-fluoro-5-[(3S)-2-[4-[(6-methylpyridazin-3-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]benzonitrile, (304)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(6-methylpyridazin-3-yl)methyl]cyclohexyl]methanone, (305)trans-[4-[[5-(2,5-dimethylpyrazole-3-yl)-3-pyridyl]methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (306)trans-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-yl]-[4-[(2-methylpyrazole-3-yl)methyl]cyclohexyl]methanone, (307)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(2-methylpyrazole-3-yl)methyl]cyclohexyl]methanone, (308)trans-[4-[[5-(1,3-dimethylpyrazole-4-yl)-3-pyridyl]methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (309)trans-[(3S)-3-(3,4-difluorophenyl)isoxazolidine-2-yl]-[4-[(2-methylpyrimidine-5-yl)methyl]cyclohexyl]methanone, (310)trans-[(3S)-3-(3,4-difluorophenyl)isoxazolidine-2-yl]-[4-[(2-methyl-[1,2,4]triazolo[1,5-b]pyridazin-6-yl)methyl]cyclohexyl]methanone, (311)trans-[(3S)-3-(3,4-difluorophenyl)isoxazolidine-2-yl]-[4-[(2-methylpyrazole-3-yl)methyl]cyclohexyl]methanone, (312)trans-3-[(3S)-2-[4-[(2,6-dimethylpyrimidine-4-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]-5-fluorobenzonitrile, (313)trans-[(3S)-3-(3,5-difluorophenyl)isoxazolidine-2-yl]-[4-[(6-methylpyrimidine-4-yl)methyl]cyclohexyl]methanone, (314)trans-[4-[(8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-yl-1,2-oxazolidine-2-yl]methanone, (315)trans-[(3S)-3-(3,5-difluorophenyl)-1,2-oxazolidine-2-yl]-[4-[(2-methyl-[1,2,4]triazolo[1,5-b]pyridazin-6-yl)methyl]cyclohexyl]methanone, (316)trans-[4-[(5-fluoro-2-methyl-3-pyridyl)methyl]cyclohexyl]-[(3S)-3-(5-methylpyrazine-2-yl)isoxazolidine-2-yl]methanone, (317)trans-[4-[(3,7-dimethyl-[1,2,4]triazolo[4,3-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(3-fluorophenyl)isoxazolidine-2-yl]methanone, (318)trans-[(3S)-3-(3,4-difluorophenyl)isoxazolidine-2-yl]-[4-[(3,7-dimethyl-[1,2,4]triazolo[4,3-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (319)trans-[4-[(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-yl]methanone, (320)trans-[4-[(8-fluoro-3-methyl-[1,2,4]triazolo[4,3-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-yl]methanone, (321)trans-[(3S)-3-(4-fluorophenyl)isoxazolidine-2-yl]-[4-[(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-7-yl)methyl]cyclohexyl]methanone, (322)trans-[2-cyano-4-[(3S)-2-[4-[(2-methylimidazo[1,2-b]pyridazin-7-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]phenyl], (323)trans-[2-fluoro-4-[(3S)-2-[4-[(2-methylimidazo[1,2-b]pyridazin-7-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]phenyl], (324)trans-[4-[(3S)-2-[4-[(2-methylimidazo[1,2-b]pyridazin-7-yl)methyl]cyclohexanecarbonyl]isoxazolidine-3-yl]phenyl], (325)trans-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(6-methyl-3-pyridyl)isoxazolidine-2-yl]methanone, (326)trans-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (327)trans-[(3S)-3-(5-fluoro-6-methyl-3-pyridyl)isoxazolidine-2-yl]-[4-[(8-fluoro-2-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)methyl]cyclohexyl]methanone, (328)trans-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-methylpyrazine-2-yl)isoxazolidine-2-yl]methanone, (329)trans-[4-[(1-methylpyrazolo[4,3-b]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (330)trans-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (331)trans-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-fluoropyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (332)trans-[4-[(2,5-dimethylpyridine-4-yl)methyl]cyclohexyl]-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (333)trans-[4-[(8-fluoro-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (334)trans-[(3S)-3-(5-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(8-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (335)trans-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(8-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (336)trans-[(3S)-3-(5-fluoropyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(8-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (337)trans-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-([1,2,4]triazolo[1,5-a]pyridine-6-ylmethyl)cyclohexyl]methanone, (338)trans-[(3S)-3-(5-fluoropyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-([1,2,4]triazolo[1,5-a]pyridine-6-ylmethyl)cyclohexyl]methanone, (339)trans-[4-[(2,5-dimethylpyridine-4-yl)methyl]cyclohexyl]-[(3S)-3-(5-methylpyrazine-2-yl)-1,2-oxazolidine-2-yl]methanone, (340)trans-[4-[(8-fluoro-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-yl-1,2-oxazolidine-2-yl]methanone, (341)trans-[4-[(8-fluoro-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (342)trans-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (343)trans-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(2-methylpyrimidine-5-yl)methyl]cyclohexyl]methanone, (344)trans-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(2-methylpyrimidine-5-yl)methyl]cyclohexyl]methanone, (345)trans-[(3S)-3-(5-fluoropyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (346)trans-[4-[(2-methylpyrimidine-5-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-yl-1,2-oxazolidine-2-yl]methanone, (347)trans-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(8-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (348)trans-[4-[[4-(3-hydroxyoxetane-3-yl)phenyl]methyl]cyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (349)trans-[4-[(2-methylimidazo[1,2-b]pyridazin-7-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-yl-1,2-oxazolidine-2-yl]methanone, (350)trans-[4-(8-fluoro-2-methyl-imidazo[1,2-a]pyridine-6-ylmethyl)-cyclohexyl]-((S)-3-pyrazine-2-yl-isoxazolidine-2-yl)-methanone, (351)trans-[4-[(8-fluoro-2-methylimidazo[1,2-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (352)trans-[4-[[4-(3-hydroxyoxetane-3-yl)phenyl]methyl]cyclohexyl]-[(3S)-3-pyrazine-2-yl-1,2-oxazolidine-2-yl]methanone, (353)trans-[4-[(2-methylimidazo[1,2-b]pyridazin-7-yl)methyl]cyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (354)trans-[4-(2,5-dimethylpyridine-4-ylmethyl)-cyclohexyl]-[(S)-3-(6-methylpyridine-3-yl)-isoxazolidine-2-yl]-methanone, (355)trans-[4-[(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-7-yl)methyl]cyclohexyl]-[(3S)-3-(5-fluoro-6-methyl-3-pyridyl)isoxazolidine-2-yl]methanone, (356)trans-[4-(2,5-dimethylpyridine-4-ylmethyl)-cyclohexyl]-((S)-3-pyrazine-2-yl-isoxazolidine-2-yl)-methanone, (357)trans-[4-[(6-methylpyridazine-3-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-ylisoxazolidine-2-yl]methanone, (358)trans-[4-[(3,5-dimethyl-[1,2,4]triazolo[4,3-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-yl-1,2-oxazolidine-2-yl]methanone, (359)trans-[4-[(8-fluoro-3-methyl-[1,2,4]triazolo[4,3-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-yl-1,2-oxazolidine-2-yl]methanone, (360)trans-(S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(2-methyl-1,3-thiazole-4-yl)methyl]cyclohexyl]methanone, (361)trans-[4-(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-ylmethyl)-cyclohexyl]-[(S)-3-(2-methyl-thiazole-4-yl)-isoxazolidine-2-yl]-methanone, (362)trans-[(S)-3-(2-methyl-thiazole-4-yl)-isoxazolidine-2-yl]-[4-(8-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-ylmethyl)-cyclohexyl]-methanone, (363)trans-[4-(8-fluoro-3-methyl-[1,2,4]triazolo[4,3-a]pyridine-6-ylmethyl)-cyclohexyl]-[(S)-3-(2-methyl-thiazole-4-yl)-isoxazolidine-2-yl]-methanone, (364)trans-[4-(8-fluoro-3-methyl-[1,2,4]triazolo[4,3-a]pyridine-6-ylmethyl)-cyclohexyl]-[(S)-3-(6-methylpyridine-3-yl)-isoxazolidine-2-yl]-methanone, (365)trans-[4-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridine-6-ylmethyl)-cyclohexyl]-[(S)-3-(6-methylpyridine-3-yl)-isoxazolidine-2-yl]-methanone, (366)trans-[4-(2,5-dimethylpyridine-4-ylmethyl)-cyclohexyl]-[(S)-3-(2-methylthiazole-4-yl)-isoxazolidine-2-yl]-methanone, (367)trans-[4-(8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-ylmethyl)-cyclohexyl]-[(S)-3-(2-methyl-thiazole-4-yl)-isoxazolidine-2-yl]-methanone, (368)trans-[4-(8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-ylmethyl)-cyclohexyl]-[(S)-3-(6-methylpyridine-3-yl)-isoxazolidine-2-yl]-methanone, (369)trans-{4-[4-(3-hydroxyoxetan-3-yl)-benzyl]-cyclohexyl}-[(S)-3-(2-methylthiazole-4-yl)-isoxazolidine-2-yl]methanone, (370)trans-[4-(8-fluoro-2-methyl-imidazo[1,2-a]pyridine-6-ylmethyl)-cyclohexyl]-[(S)-3-(2-methyl-thiazole-4-yl)-isoxazolidine-2-yl]-methanone, (371)trans-[4-(2-methyl-imidazo[1,2-b]pyridazine-7-ylmethyl)-cyclohexyl]-[(S)-3-(2-methyl-thiazole-4-yl)-isoxazolidine-2-yl]-methanone, (372)trans-[(S)-3-(2-methyl-thiazole-4-yl)-isoxazolidine-2-yl]-[4-(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-7-ylmethyl)-cyclohexyl]-methanone, (373)trans-[(S)-3-(6-methylpyridine-3-yl)-isoxazolidine-2-yl]-[4-(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-7-ylmethyl)-cyclohexyl]-methanone, (374)trans-[4-(2-methyl-[1,2,4]triazolo[1,5-a]pyridine-7-ylmethyl)-cyclohexyl]-((S)-3-pyrazine-2-yl-isoxazolidine-2-yl)-methanone, (375)trans-[4-(3,5-dimethyl-[1,2,4]triazolo[4,3-a]pyridine-6-ylmethyl)-cyclohexyl]-[(S)-3-(2-methyl-thiazole-4-yl)-isoxazolidine-2-yl]-methanone, (376)trans-[4-(3,5-dimethyl-[1,2,4]triazolo[4,3-a]pyridine-6-ylmethyl)-cyclohexyl]-[(S)-3-(6-methylpyridine-3-yl)-isoxazolidine-2-yl]-methanone, (377)trans-[4-[(2,5-dimethylpyridine-4-yl)methyl]cyclohexyl]-[(3S)-3-(2-methyl-1,3-oxazol-4-yl)-1,2-oxazolidine-2-yl]methanone, (378)trans-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (379)trans-[4-[(8-fluoro-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-methylpyrazine-2-yl)-1,2-oxazolidine-2-yl]methanone, (380)trans-[4-[(8-fluoro-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-fluoropyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (381)trans-[4-[(8-chloro-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (382)trans-[4-[(8-chloro-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-fluoropyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (383)trans-[4-[(8-methoxy-2-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (384)trans-[4-[(5-fluoro-2-methylpyridine-4-yl)methyl]cyclohexyl]-[(3S)-3-(5-methylpyrazine-2-yl)-1,2-oxazolidine-2-yl]methanone, (385)trans-[4-[(5-chloro-2-methylpyridine-4-yl)methyl]cyclohexyl]-[(3S)-3-(5-methylpyrazine-2-yl)-1,2-oxazolidine-2-yl]methanone, (386)trans-[4-[(5-fluoro-2-methylpyridine-4-yl)methyl]cyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (387)trans-[4-[(6-methylpyridazine-3-yl)methyl]cyclohexyl]-[(3S)-3-(6-methylpyridin-3-yl)-1,2-oxazolidine-2-yl]methanone, (388)trans-[4-[(6-methylpyridazine-3-yl)methyl]cyclohexyl]-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (389)trans-[4-[(5-chloro-2-methylpyridine-4-yl)methyl]cyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (390)trans-[4-[(8-fluoro-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (391)trans-[4-[(2-amino-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (392)trans-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(8-fluoro-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (393)trans-[4-[(2,4-dimethylpyrimidine-5-yl)methyl]cyclohexyl]-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (394)trans-[4-[(5-fluoro-2-methylpyridine-4-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-yl-1,2-oxazolidine-2-yl]methanone, (395)trans-[(3S)-3-(5-methylpyrazine-2-yl)-1,2-oxazolidine-2-yl]-[4-[(2-methylpyrazole-3-yl)methyl]cyclohexyl]methanone, (396)trans-[4-[(5-chloro-2-methylpyridine-4-yl)methyl]cyclohexyl]-[(3S)-3-pyrazine-2-yl-1,2-oxazolidine-2-yl]methanone, (397)trans-[4-[(2-methylpyrazole-3-yl)methyl]cyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (398)trans-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(6-methylpyridazine-4-yl)methyl]cyclohexyl]methanone, (399)trans-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[[2-methyl-4-(trifluoromethyl)pyrimidine-5-yl]methyl]cyclohexyl]methanone, (400)trans-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]-1-methylcyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (401)trans-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]-1-methylcyclohexyl]-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (402) cis-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]-1-methylcyclohexyl]-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (403) cis-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]-1-methylcyclohexyl]-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (404)trans-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]-[4-[(2-methylpyrazole-3-yl)methyl]cyclohexyl]methanone, (405) cis-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]-4-methylcyclohexyl]-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (406) cis-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]-4-methylcyclohexyl]-[(3S)-3-(5-fluoro-6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (407) cis-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]-4-methylcyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (408)trans-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]-4-methylcyclohexyl]-[(3S)-3-(6-methylpyridine-3-yl)-1,2-oxazolidine-2-yl]methanone, (409)trans-[(3S)-3-(5-methylpyrazine-2-yl)-1,2-oxazolidine-2-yl]-[4-[(8-methyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]methanone, (410)trans-[4-[(1,3-dimethylpyrazolo[4,3-b]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(5-methylpyrazine-2-yl)-1,2-oxazolidine-2-yl]methanone, and (411)trans-[4-[(2,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine-6-yl)methyl]cyclohexyl]-[(3S)-3-(6-methylpyrazine-2-yl)isoxazolidine-2-yl]methanone A compound of formula (I) according to any one of claims 1 to 13, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, selected from among.
15. A pharmaceutical composition comprising a compound of formula (I) according to any one of claims 1 to 13 or a compound according to claim 14, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, and at least one pharmaceutically acceptable excipient.
16. A pharmaceutical product comprising a compound of formula (I) according to any one of claims 1 to 13, or a compound according to claim 14, or a pharmaceutically acceptable salt thereof.
17. A compound of formula (I) according to any one of claims 1 to 13, or a compound according to claim 14, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, for use as a pharmaceutical.
18. A compound of formula (I) according to any one of claims 1 to 13 or a compound according to claim 14, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, for use in the treatment and / or prevention of diseases, disorders or conditions mediated at least partially by receptor-interacting protein kinase 1.
19. A compound of formula (I) according to any one of claims 1 to 13 or the compound according to claim 14, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, for use in the treatment and / or prevention of a disease selected from Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS).