Carboxamides as ubiquitin-specific protease inhibitors

1. A compound of Formula (I):

or a pharmaceutically acceptable form thereof, wherein

Y is chosen from C(R 3 ) and N;

R′ is chosen from H and CH 3 ;

R 1 is chosen from 6-11 membered heteroaryls optionally substituted with one or more substituents chosen from R 5 or R 6 ;

R 2 is chosen from N-linked 4-12 membered heterocyclyls and C-linked 4-12 membered heterocyclyls, wherein the heterocyclyls are optionally substituted with one or more R 5 , and further wherein any R 2 group containing hydrogen can have one or more hydrogens replaced with deuterium;

each R 3 is independently chosen from H, deuterium, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, halogen, —OH, —CN, wherein each of (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups are optionally substituted with one or more R 7 ;

R 4 is chosen from H, deuterium, (C 1 -C 6 ) alkyl, halogen, —OH, —CN, and further wherein any R 4 group containing hydrogen can have one or more hydrogens replaced with deuterium;

each R 5 (if present) is independently chosen from —OH, —NH 2 , NHC(O)CH 3 , —C(O)NHCH 3 , (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, halogen, cycloalkyl, heterocycloalkyl, and —C(O)-heterocycloalkyl groups, wherein each of —NH 2 , —NHC(O)CH 3 , —C(O)NHCH 3 , (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, cycloalkyl, heterocycloalkyl, and —C(O)-heterocycloalkyl are optionally substituted with one or more substituents independently chosen from (C 1 -C 6 ) alkoxy, —NH 2 , and —OH, and wherein any R 5 group containing hydrogen can have one or more hydrogens replaced with deuterium;

each R 6 (if present) is chosen from —NH(C 1 -C 6 )alkyl-aryls, —NH(C 1 -C 6 )alkyl-heteroaryls, —NH(C 1 -C 6 )alkyl-heterocyclyl groups, and —NH(C 1 -C 6 )alkyl-heterocyclyl groups, wherein each of the R 6 groups are optionally substituted with one or more substituents chosen from —OH, —NH, halogens, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, and (C 1 -C 6 ) haloalkyl groups, and further wherein any R 6 group containing hydrogen can have one or more hydrogens replaced with deuterium;

each R 7 is independently chosen from —OH, —NH 2 , (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, halogen, cycloalkyl, —C(O)-cycloalkyl, heterocycloalkyl, and —C(O)-heterocycloalkyl groups, wherein each of —NH 2 , (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, halogen, cycloalkyl, —C(O)-cycloalkyl, heterocycloalkyl, and —C(O)-heterocycloalkyl are optionally substituted with one or more substituents independently chosen from (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, and —OH; and

n is 0, 1, 2, or 3.

2. The compound of claim 1 , of Formula (II):

or a pharmaceutically acceptable form thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and n are all as defined for Formula (I).

3. The compound of claim 1 , of Formula (III):

or a pharmaceutically acceptable form thereof, wherein

R 1 is chosen from 8-11 membered heteroaryls optionally substituted with one or more R 5 ;

R 2 is chosen from N-linked 4-12 membered heterocyclyls and C-linked 4-12 membered heterocyclyls, optionally substituted with one or more R 5 ;

each R 5 (if present) is independently chosen from —OH, —NH 2 , NHC(O)CH 3 , (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, halogen, cycloalkyl, heterocycloalkyl, and —C(O)— heterocycloalkyl groups, wherein each of —NH 2 , —NHC(O)CH 3 , (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, cycloalkyl, heterocycloalkyl, and —C(O)-heterocycloalkyl are optionally substituted with one or more substituents independently chosen from (C 1 -C 6 ) alkoxy, —NH 2 , and —OH; and

n is 0, 1, 2, or 3.

4. The compound of claim 1 , of Formula (IV):

and pharmaceutically acceptable forms thereof, wherein R′, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and n are all as defined for Formula (I).

5. The compound of claim 1 , of Formula (V):

or a pharmaceutically acceptable form thereof, wherein

R 1 is chosen from 8-9 membered heteroaryls optionally substituted with one or more R 5 ;

R 2 is chosen from N-linked 4-12 membered heterocyclyls optionally substituted with one or more R 5 ;

each R 5 (if present) is independently chosen from —OH, —NH 2 , NHC(O)CH 3 , (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, halogen, cycloalkyl, heterocycloalkyl, and —C(O)— heterocycloalkyl groups, wherein each of —NH 2 , —NHC(O)CH 3 , (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, cycloalkyl, heterocycloalkyl, and —C(O)-heterocycloalkyl are optionally substituted with one or more substituents independently chosen from (C 1 -C 6 ) alkoxy, —NH 2 , and —OH; and

n is 0, 1, 2, or 3.

6. The compound of claim 1 , wherein R 1 , optionally substituted with R 5 or R 6 , is chosen from

7. The compound of claim 1 , wherein R 2 , optionally substituted with R 5 , is chosen from

8. The compound of claim 1 , wherein R 1 , optionally substituted with R 5 or R 6 , is chosen from

and R 2 , optionally substituted with R 5 , is chosen from

9. The compound of claim 1 , wherein R 1 is chosen from

wherein B is chosen from a bond or C;

Z is chosen from N, S, and C(Rii);

Rii is chosen from H, CH 3 and R 5 ;

R 2 is chosen from N-linked 5-8 membered heterocyclyls substituted with one to three R 5 ;

each R 5 (if present) is independently chosen from —OH, —NH 2 , NHC(O)CH 3 , (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, halogen, cycloalkyl, heterocycloalkyl, and —C(O)— heterocycloalkyl groups, wherein each of —NH 2 , —NHC(O)CH 3 , (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 1 -C 6 ) haloalkyl, (C 1 -C 6 ) haloalkoxy, cycloalkyl, heterocycloalkyl, and —C(O)-heterocycloalkyl are optionally substituted with one or more substituents independently chosen from (C 1 -C 6 ) alkoxy, —NH 2 , and —OH; and

n is 0, 1, 2, or 3.

10. The compound of claim 1 , wherein

R 1 , optionally substituted with R 5 , is chosen from

and

R 2 , optionally substituted with R 5 , is chosen from

11. The compound of claim 1 , wherein the compound is

a. a compound having an USP28 IC 50 of 0.001-2 micromolar or

b. a compound having an USP25 IC 50 of 0.001-2 micromolar.

12. The compound of claim 1 , chosen from the following compounds:

23-1: 7-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-methoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-3-methylthieno[2,3-b]pyrazine-6-carboxamide;

23-2: 7-amino-N-[(6R)-2-[(3S,4S)-3-amino-4-methoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-3-methylthieno[2,3-b]pyrazine-6-carboxamide;

23-3: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-methoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide;

23-4: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-methoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

23-5: 3-amino-N-[(6R)-2-[(3S,4S)-3-amino-4-methoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

23-6: 7-amino-3-methyl-N-[(6S)-2-(piperazin-1-yl)-5,6,7,8-tetrahydroquinolin-6-yl]thieno[2,3-b]pyrazine-6-carboxamide;

23-7: 3-amino-6-methyl-N-[(6S)-2-(piperazin-1-yl)-5,6,7,8-tetrahydroquinolin-6-yl]thieno[2,3-b]pyridine-2-carboxamide;

23-8: 3-amino-6-methyl-N-[(6R)-2-(piperazin-1-yl)-5,6,7,8-tetrahydroquinolin-6-yl]thieno[2,3-b]pyridine-2-carboxamide;

23-9: 6-amino-2-methyl-N-[(6S)-2-(piperazin-1-yl)-5,6,7,8-tetrahydroquinolin-6-yl]thieno[2,3-d][1,3]thiazole-5-carboxamide;

23-12: 3-amino-N-[(6S)-2-{3,8-diazabicyclo[3.2.1]octan-3-yl}-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

23-13: 7-amino-N-[(6S)-2-{3,8-diazabicyclo[3.2.1]octan-3-yl}-5,6,7,8-tetrahydroquinolin-6-yl]-3-methylthieno[2,3-b]pyrazine-6-carboxamide;

23-14: 3-amino-4,6-dimethyl-N-[(6S)-2-(piperazin-1-yl)-5,6,7,8-tetrahydroquinolin-6-yl]thieno[2,3-b]pyridine-2-carboxamide;

23-17: 3-amino-N-[(6S)-4-fluoro-2-(piperazin-1-yl)-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

23-18: 3-amino-N-[(6S)-2-{3,8-diazabicyclo[3.2.1]octan-3-yl}-4-fluoro-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

24-1: 3-amino-N-[(6S)-2-[(3R,4R)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

24-2: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

25: 3-amino-N-[(6S)-2-[(3S,4R)-3-amino-4-(difluoromethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

26-1: 3-amino-N-[(6S)-2-[(3S,4R)-3-(methoxymethyl)-4-(methylamino)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

26-2: 3-amino-N-[(6S)-2-[(3R,4S)-3-(methoxymethyl)-4-(methylamino)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

27-1: 3-amino-N-[(6S)-2-[(3R,4R)-3-amino-4-(fluoromethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

27-2: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-(fluoromethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

28-1: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-(2-methoxyethoxy)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

28-2: 3-amino-N-[(6S)-2-[(3R,4R)-3-amino-4-(2-methoxyethoxy)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

29-1: 3-amino-N-[(6S)-2-[(9S)-9-amino-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

29-2: 3-amino-N-[(6S)-2-[(9R)-9-amino-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

30-1: 3-amino-N-[(6S)-3-fluoro-2-(piperazin-1-yl)-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

30-2: 3-amino-N-[(6R)-3-fluoro-2-(piperazin-1-yl)-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

31-3: 3-amino-6-methyl-N-[(6'S)-2′-(piperazin-1-yl)-6′,7′-dihydro-5′H-spiro[cyclopropane-1,8′-quinoline]-6′-yl]thieno[2,3-b]pyridine-2-carboxamide;

31-4: 3-amino-6-methyl-N-[(6′R)-2′-(piperazin-1-yl)-6′,7′-dihydro-5′H-spiro[cyclopropane-1,8′-quinoline]-6′-yl]thieno[2,3-b]pyridine-2-carboxamide;

142: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-ethoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

203: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-methoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-5-fluoro-6-methylthieno[2,3-b]pyridine-2-carboxamide;

204: 3-amino-5-fluoro-6-methyl-N-[(6S)-2-(piperazin-1-yl)-5,6,7,8-tetrahydroquinolin-6-yl]thieno[2,3-b]pyridine-2-carboxamide;

205: 3-amino-6-methyl-N-[(6S,8S)-8-methyl-2-(piperazin-1-yl)-5,6,7,8-tetrahydroquinolin-6-yl]thieno[2,3-b]pyridine-2-carboxamide;

206: 3-amino-6-methyl-N-[(6R,8S)-8-methyl-2-(piperazin-1-yl)-5,6,7,8-tetrahydroquinolin-6-yl]thieno[2,3-b]pyridine-2-carboxamide;

207: 3-amino-6-methyl-N-[(6S,8R)-8-methyl-2-(piperazin-1-yl)-5,6,7,8-tetrahy droquinolin-6-yl]thieno[2,3-b]pyridine-2-carboxamide;

208: 3-amino-6-methyl-N-[(6R,8R)-8-methyl-2-(piperazin-1-yl)-5,6,7,8-tetrahy droquinolin-6-yl]thieno[2,3-b]pyridine-2-carboxamide;

210: 3-amino-N-[(6S)-2-[(3S,4S)-4-amino-3-methoxy-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

211: 3-amino-N-[(6S)-2-[(3R,4R)-4-amino-3-methoxy-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

239: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-methoxy-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

240: 3-amino-N-[(6S)-2-[(3R,4R)-3-amino-4-methoxy-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

254: 3-amino-N-[(6S)-2-[(3S,4R)-3-amino-4-ethoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

255: 3-amino-N-[(6S)-2-[(3R,4S)-3-amino-4-ethoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

269: 3-amino-N-[(6S)-2-[(3S,4R)-3-amino-4-methoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

270: 3-amino-N-[(6S)-2-[(3R,4S)-3-amino-4-methoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

279: 7-amino-N-[(6S)-2-[(3S,4S)-4-amino-3-methoxy-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-3-methylthieno[2,3-b]pyrazine-6-carboxamide;

280: 7-amino-N-[(6S)-2-[(3R,4R)-4-amino-3-methoxy-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-3-methylthieno[2,3-b]pyrazine-6-carboxamide;

285: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-cyclobutoxypyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

296: 3-amino-N-[(6S)-2-[(3R,4R)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide;

297: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide;

298: 7-amino-N-[(6S)-2-[(3R,4R)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-3-methylthieno[2,3-b]pyrazine-6-carboxamide;

299: 7-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-3-methylthieno[2,3-b]pyrazine-6-carboxamide;

300: 3-amino-N-[(6S)-2-[(3R,4R)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-3-fluoro-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

301: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-3-fluoro-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

302: 3-amino-N-[(6R)-2-[(3R,4R)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-3-fluoro-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

303: 3-amino-N-[(6R)-2-[(3S,4S)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-3-fluoro-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

311: 3-amino-N-[(6S)-2-[(3S,4S)-3-methoxy-4-(methylamino)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

312: 3-amino-N-[(6S)-2-[(3S,4S)-3-methoxy-4-(methylamino)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide;

320: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-(propan-2-yloxy)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

321: 3-amino-N-[(6S)-2-[(3S,4R)-3-amino-4-(propan-2-yloxy)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

322: 3-amino-N-[(6S)-2-[(3R,4S)-3-amino-4-(propan-2-yloxy)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

327: 3-amino-N-[(6S)-2-[(3R,4S)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

328: 3-amino-N-[(6S)-2-[(3S,4R)-3-amino-4-(methoxymethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

331: 3-amino-N-[(6S)-2-[(3R,4S)-3-hydroxy-3-methyl-4-(methylamino)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

332: 3-amino-N-[(6S)-2-[(3S,4R)-3-hydroxy-3-methyl-4-(methylamino)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

341: 3-amino-N-[(6S)-2-[(3S,4R)-4-amino-3-(methoxymethyl)-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

342: 3-amino-N-[(6S)-2-[(3R,4R)-4-amino-3-(methoxymethyl)-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

343: 3-amino-N-[(6S)-2-[(3S,4S)-4-amino-3-(methoxymethyl)-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

344: 3-amino-N-[(6S)-2-[(3R,4S)-4-amino-3-(methoxymethyl)-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

345: 3-amino-N-[(6S)-2-[(3R,4R)-3-amino-4-(difluoromethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

346: 3-amino-N-[(6S)-2-[(3S,4S)-3-amino-4-(difluoromethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

347: 3-amino-N-[(6S)-2-[(3R,4S)-3-amino-4-(difluoromethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

354: 3-amino-N-[(6S)-2-{3,8-diazabicyclo[3.2.1]octan-3-yl}-5,6,7,8-tetrahydroquinolin-6-yl]-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide;

363: 3-amino-N-[(6S)-2-[(3R,4S)-3-amino-4-(trifluoromethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

364: 3-amino-N-[(6S)-2-[(3S,4R)-3-amino-4-(trifluoromethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

376: 3-amino-N-[(6S)-2-[(3S,4R)-3-(difluoromethyl)-4-(methylamino)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

377: 3-amino-N-[(6S)-2-[(3R,4S)-3-(difluoromethyl)-4-(methylamino)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

384: 3-amino-N-[(6S)-2-[(3R,4S)-3-amino-4-(fluoromethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

385: 3-amino-N-[(6S)-2-[(3S,4R)-3-amino-4-(fluoromethyl)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

427: 3-amino-N-[(6S)-2-[(3R,4S)-4-amino-3-methoxy-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

428: 3-amino-N-[(6S)-2-[(3S,4R)-4-amino-3-methoxy-3-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

430: 3-amino-N-[(6S)-2-[(5S,9R)-9-amino-2-oxa-7-azaspiro[4.4]nonan-7-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

431: 3-amino-N-[(6S)-2-[(5R,9S)-9-amino-2-oxa-7-azaspiro[4.4]nonan-7-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

437: 3-amino-N-[(6S)-2-[(5R,9R)-9-amino-2-oxa-7-azaspiro[4.4]nonan-7-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide;

441: 3-amino-N-[(6S)-2-[(3R,4R)-3-(fluoromethyl)-4-(methylamino)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide; and

442: 3-amino-N-[(6S)-2-[(3S,4S)-3-(fluoromethyl)-4-(methylamino)pyrrolidin-1-yl]-5,6,7,8-tetrahydroquinolin-6-yl]-6-methylthieno[2,3-b]pyridine-2-carboxamide.

13. A composition comprising at least one compound of claim 1 , and a biologically acceptable carrier.

14. The compound of claim 1 , wherein R 1 , optionally substituted with R 5 or R 6 , is chosen from

15. The compound of claim 1 , wherein R 2 , optionally substituted with R 5 , is chosen from