Claims for Patent: 9,598,422

Summary for Patent: 9,598,422

Title:	Immunoregulatory agents
Abstract:	Compounds that modulate the oxidoreductase enzyme indoleamine 2,3-dioxygenase, and compositions containing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by indoleamine 2,3-dioxygenase is also provided.
Inventor(s):	Beck; Hilary Plake (Emerald Hills, CA), Jaen; Juan Carlos (Burlingame, CA), Osipov; Maksim (Belmont, CA), Powers; Jay Patrick (Pacifica, CA), Reilly; Maureen Kay (Belmont, CA), Shunatona; Hunter Paul (San Francisco, CA), Walker; James Ross (Menlo Park, CA), Zibinsky; Mikhail (Lodi, CA), Balog; James Aaron (Lambertville, NJ), Williams; David K. (Delran, NJ), Markwalder; Jay A. (Lahaska, PA), Seitz; Steven P. (Swarthmore, PA), Cherney; Emily Charlotte (Newtown, PA), Zhang; Liping (East Windsor, NJ), Shan; Weifang (Princeton, NJ), Guo; Weiwei (Lawrenceville, NJ), Huang; Audris (New Hope, PA)
Assignee:	Flexus Biosciences, Inc. (Princeton, NJ)
Application Number:	14/933,879
Patent Claims:	1. A compound of the formula (I): ##STR00261## or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein, the subscript n is 1; A is --C(O)--; B is --NH--; T is --CR.sup.3R.sup.4--; D is C(R.sup.5); E is C(R.sup.6); V is a bond; G is an optionally substituted quinolinyl; J.sup.1 is CH or C(R.sup.2), when R.sup.2 is attached to the ring vertex identified as J.sup.1; R.sup.1 and R.sup.2 are independently hydrogen, halogen, optionally substituted C.sub.1-C.sub.4 haloalkyl, optionally substituted C.sub.3-C.sub.6 cycloalkyl, optionally substituted 3- to 6-membered cycloheteroalkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted C.sub.1-C.sub.4 alkyl, optionally substituted C.sub.1-C.sub.4 alkoxy, CN, SO.sub.2NH.sub.2, NHSO.sub.2CH.sub.3, NHSO.sub.2CF.sub.3, OCF.sub.3, SO.sub.2CH.sub.3, SO.sub.2CF.sub.3, or CONH.sub.2, and when R.sup.1 and R.sup.2 are on adjacent vertices of a phenyl ring they may be joined together to form a 5- or 6-membered cycloheteroalkyl ring having one or two ring vertices independently selected from O, N and S, wherein said cycloheteroalkyl ring is optionally substituted with from one to three members selected from fluoro and C.sub.1-C.sub.3 alkyl; R.sup.3 and R.sup.4 are independently hydrogen, optionally substituted C.sub.1-C.sub.6 alkyl, optionally substituted C.sub.1-C.sub.6 haloalkyl, fluorine, OH, CN, CO.sub.2H, C(O)NH.sub.2, N(R.sup.5a).sub.2, optionally substituted --O--C.sub.1-C.sub.6 alkyl, --(CR.sup.5R.sup.5).sub.m--OH, --(CR.sup.5R.sup.5).sub.m--CO.sub.2H, --(CR.sup.5R.sup.5).sub.m--C(O)NH.sub.2, --(CR.sup.5R.sup.5).sub.m--C(O)NHR.sup.5a, --(CR.sup.5R.sup.5).sub.mN(R.sup.5a).sub.2, --NH(CR.sup.5R.sup.5).sub.mCO.sub.2H or --NH(CR.sup.5R.sup.5).sub.m--C(O)NH.sub.2; each R.sup.5 is independently H, F, OH, optionally substituted C.sub.1-C.sub.6 alkyl or optionally substituted --O--C.sub.1-C.sub.6 alkyl; each R.sup.5a is independently H, or optionally substituted C.sub.1-C.sub.6 alkyl; R.sup.6 is H, OH, F, optionally substituted C.sub.1-C.sub.6 alkyl, optionally substituted --O--C.sub.1-C.sub.6 alkyl, or --N(R.sup.5a).sub.2; and each m is independently 1, 2, or 3. 2. The compound of claim 1, of the formula: ##STR00262## 3. The compound of claim 1, of the formula: ##STR00263## 4. The compound of claim 1, of the formula: ##STR00264## 5. The compound of claim 1, of the formula: ##STR00265## 6. The compound of claim 1 that is: 4-Chloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)ben- zamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)benza- mide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-2-meth- ylbenzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-3-methylben- zamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-me- thylbenzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-2-methoxybe- nzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-3-m- ethoxybenzamide; 2-fluoro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)ben- zamide; 3-fluoro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)et- hyl)benzamide; 2-chloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)ben- zamide; 3-chloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)et- hyl)benzamide; 3,4-dichloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl- )benzamide; 4-fluoro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)ben- zamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-[1,1- '-biphenyl]-3-carboxamide; 3,5-dichloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl- )benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-methoxybe- nzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-[1,- 1'-biphenyl]-2-carboxamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-[1,1'-biphe- nyl]-4-carboxamide; 4-Chloro-N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propyl)benzam- ide; 4-Chloro-N--((S)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propyl)be- nzamide; 4-Chloro-N--((R)-1-(trans-4-(6-fluoroquinolin-4-yl)cyclohexyl)pro- pyl)benzamide; 4-Chloro-N--((S)-1-(trans-4-(6-fluoroquinolin-4-yl)cyclohexyl)propyl)benz- amide; 4-Cyano-N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propyl)b- enzamide; 4-Cyano-N--((S)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propy- l)benzamide; 4-Cyano-N--((R)-1-(trans-4-(6-fluoroquinolin-4-yl)cyclohexyl)propyl)benza- mide; 4-Cyano-N--((S)-1-(trans-4-(6-fluoroquinolin-4-yl)cyclohexyl)propyl)- benzamide; 4-cyano-N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethy- l)benzamide; 5-(3-fluoro-4-methoxyphenyl)-N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cycl- ohexyl)ethyl)picolinamide; (R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)-N-methylethanamine; N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1H-pyrrol-1-- yl)benzamide; N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1H-imidazol-- 1-yl)benzamide; 4-chloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)but-3-en-- 1-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)but-3-en-1-yl)-[1,- 1'-biphenyl]-4-carboxamide N-1-((1 S,4S)-4-(quinolin-3-yl)cyclohexyl)propyl)-[1,1'-biphenyl]-4-carboxamide; N-(1-((1R,4R)-4-(quinolin-3-yl)cyclohexyl)propyl)-[1,1'-biphenyl]-4-carbo- xamide; N--((R)-1-((1s,4S)-4-(quinolin-3-yl)cyclohexyl)propyl)-[1,1'-biphe- nyl]-4-carboxamide; N--((S)-1-((1s,4R)-4-(quinolin-3-yl)cyclohexyl)propyl)-[1,1'-biphenyl]-4-- carboxamide; N--((R)-1-((1r,4R)-4-(quinolin-3-yl)cyclohexyl)propyl)-[1,1'-biphenyl]-4-- carboxamide; N--((S)-1-((1r,4S)-4-(quinolin-3-yl)cyclohexyl)propyl)-[1,1'-biphenyl]-4-- carboxamide; 4-chloro-N--((R)-1-(cis-4-(quinolin-3-yl)cyclohexyl)propyl)benzamide; 4-chloro-N--((S)-1-(cis-4-(quinolin-3-yl)cyclohexyl)propyl)benzamide; 4-chloro-N--((R)-1-(trans-4-(quinolin-3-yl)cyclohexyl)propyl)benzamide; 4-chloro-N--((S)-1-(trans-4-(quinolin-3-yl)cyclohexyl)propyl)benzamide; N-(1-((1s,4s)-4-(6-(trifluoromethyl)quinolin-4-yl)cyclohexyl)propyl)biphe- nyl-4-carboxamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(5-methyl- -1,3,4-oxadiazol-2-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(pyrazin-- 2-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(pyrimidi- n-5-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1-methyl- -1H-imidazol-4-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(2-methox- ypyrimidin-4-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(6-methyl- sulfonyl)pyridin-3-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(2-methyl- thiazol-5-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(5-methox- ypyridin-2-yl)benzamide; 4-(2-cyanopyrimidin-5-yl)-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyc- lohexyl)ethyl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(2-methox- ythiazol-4-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4'-(2-hydro- xypropan-2-yl)biphenyl-4-carboxamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(thiazol-- 4-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1,3,4-ox- adiazol-2-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(6-methox- ypyridin-3-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-morpholin- obenzamide; 4-cyclopropyl-N--((R)-1((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl- )benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1-methyl- cyclopropyl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(trifluor- omethyl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(oxazol-5- -yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1-methyl- -1H-1,2,4-triazol-5-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(5-methyl- thiazol-2-yl)benzamide; 4-(5-cyanothiazol-2-yl)-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclo- hexyl)ethyl)benzamide; 4-chloro-N-(1-((1s,4s)-4-(6-(trifluoromethyl)quinolin-4-yl)cyclohexyl)pro- pyl)benzamide; 4-(1H-pyrrol-1-yl)-N-(1-((1s,4S)-4-(6-(trifluoromethyl)quinolin-4-yl)cycl- ohexyl)propyl)benzamide; N-(1-(4-(6-fluoroquinolin-4-yl)cyclohexyl)propyl)-4-(thiazol-2-yl)benzami- de; or N-(1-(4-(6-fluoroquinolin-4-yl)cyclohexyl)propyl)bi-phenyl-4-carbox- amide; or a pharmaceutically acceptable salt thereof. 7. A pharmaceutical composition comprising a compound of claim 1, and a pharmaceutically acceptable excipient. 8. A combination comprising a compound of claim 1 and at least one additional therapeutic agent. 9. The combination of claim 8, wherein the at least one additional therapeutic agent is a chemotherapeutic agent, an immune- and/or inflammation-modulating agent, an anti-hypercholesterolemia agent, or an anti-infective agent. 10. The combination of claim 8, wherein the at least one additional therapeutic agent is an immune checkpoint inhibitor. 11. The combination of claim 10, wherein said immune checkpoint inhibitor is selected from the group consisting of ipilimumab, nivolumab and pembrolizumab. 12. The compound of claim 1, wherein G is unsubstituted. 13. The compound of claim 1, wherein G is substituted. 14. The compound of claim 13, wherein the G is substituted with halogen. 15. The compound of claim 1, wherein R.sup.5 is H or C.sub.1-C.sub.6alkyl. 16. The compound of claim 1, wherein R.sup.5 is H. 17. The compound of claim 1, wherein R.sup.6 is H, OH, F, C.sub.1-C.sub.6 alkyl, --O--C.sub.1-C.sub.6 alkyl, or --N(R.sup.5a).sub.2. 18. The compound of claim 1, wherein R.sup.6 is H or C.sub.1-C.sub.6 alkyl. 19. The compound of claim 1, wherein R.sup.6 is H. 20. The compound of claim 1, wherein R.sup.3 and R.sup.4 are independently hydrogen or optionally substituted C.sub.1-C.sub.6 alkyl. 21. The compound of claim 1, wherein R.sup.3 and R.sup.4 are independently hydrogen or C.sub.1-C.sub.6 alkyl. 22. The compound of claim 1 that is: 4-Chloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)ben- zamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)benza- mide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-2-meth- ylbenzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-3-methylben- zamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-me- thylbenzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-2-methoxybe- nzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-3-m- ethoxybenzamide; 2-fluoro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)ben- zamide; 3-fluoro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)et- hyl)benzamide; 2-chloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)ben- zamide; 3-chloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)et- hyl)benzamide; 3,4-dichloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl- )benzamide; 4-fluoro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)ben- zamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-[1,1- '-biphenyl]-3-carboxamide; 3,5-dichloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl- )benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-methoxybe- nzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-[1,- 1'-biphenyl]-2-carboxamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-[1,1'-biphe- nyl]-4-carboxamide; 4-cyano-N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)benzamid- e; 5-(3-fluoro-4-methoxyphenyl)-N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cy- clohexyl)ethyl)picolinamide; (R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)-N-methylethanamine; N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1H-pyrrol-1-- yl)benzamide; N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1H-imidazol-- 1-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(5-methyl- -1,3,4-oxadiazol-2-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(pyrazin-- 2-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(pyrimidi- n-5-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1-methyl- -1H-imidazol-4-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(2-methox- ypyrimidin-4-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(6-methyl- sulfonyl)pyridin-3-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(2-methyl- thiazol-5-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(5-methox- ypyridin-2-yl)benzamide; 4-(2-cyanopyrimidin-5-yl)-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyc- lohexyl)ethyl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(2-methox- ythiazol-4-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4'-(2-hydro- xypropan-2-yl)biphenyl-4-carboxamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(thiazol-- 4-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1,3,4-ox- adiazol-2-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(6-methox- ypyridin-3-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-morpholin- obenzamide; 4-cyclopropyl-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethy- l)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1-methyl- cyclopropyl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(trifluor- omethyl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(oxazol-5- -yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1-methyl- -1H-1,2,4-triazol-5-yl)benzamide; N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(5-methyl- thiazol-2-yl)benzamide; or 4-(5-cyanothiazol-2-yl)-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclo- hexyl)ethyl)benzamide; or a pharmaceutically acceptable salt thereof. 23. The compound of claim 1 that is 4-Chloro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)ben- zamide or a pharmaceutically acceptable salt thereof. 24. The compound of claim 1 that is N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-methylben- zamide or a pharmaceutically acceptable salt thereof. 25. The compound of claim 1 that is 4-fluoro-N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)ben- zamide or a pharmaceutically acceptable salt thereof. 26. The compound of claim 1 that is N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-methoxybe- nzamide or a pharmaceutically acceptable salt thereof. 27. The compound of claim 1 that is N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-[1,1'-biphe- nyl]-4-carboxamide or a pharmaceutically acceptable salt thereof. 28. The compound of claim 1 that is 4-cyano-N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)benzamid- e or a pharmaceutically acceptable salt thereof. 29. The compound of claim 1 that is (R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)-N-methylethanamine or a pharmaceutically acceptable salt thereof. 30. The compound of claim 1 that is N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1H-pyrrol-1-- yl)benzamide or a pharmaceutically acceptable salt thereof. 31. The compound of claim 1 that is N--((R)-1-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1H-imidazol-- 1-yl)benzamide or a pharmaceutically acceptable salt thereof. 32. The compound of claim 1 that is N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(5-methyl- -1,3,4-oxadiazol-2-yl)benzamide or a pharmaceutically acceptable salt thereof. 33. The compound of claim 1 that is N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(thiazol-- 4-yl)benzamide or a pharmaceutically acceptable salt thereof. 34. The compound of claim 1 that is N--((R)-1-((1s,4S)-4-(6-fluoroquinolin-4-yl)cyclohexyl)ethyl)-4-(1,3,4-ox- adiazol-2-yl)benzamide or a pharmaceutically acceptable salt thereof.

Details for Patent 9,598,422

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bristol-myers Squibb Company	YERVOY	ipilimumab	Injection	125377	03/25/2011		2034-11-05
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	For Injection	125514	09/04/2014		2034-11-05
Merck Sharp & Dohme Corp.	KEYTRUDA	pembrolizumab	Injection	125514	01/15/2015		2034-11-05
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	12/22/2014		2034-11-05
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	10/04/2017		2034-11-05
Bristol-myers Squibb Company	OPDIVO	nivolumab	Injection	125554	08/27/2021		2034-11-05