Heterocyclic compounds and uses thereof

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 9,718,847
App. No.: 14/486,986
Granted: Aug 1, 2017
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Heterocyclic compounds of formula (I), methods for their preparation, pharmaceutical compositions containing such a compound and their therapeutic uses.

Claims (46)

1. A compound having formula (Va):

or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof,

wherein:

R 2 is H;

R 4 is H;

R 6 is H;

R 7 is H, —OH, C 1-6 alkyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;

R 1 is heteroaryl optionally substituted with from 1-3 R j groups;

each R j independently selected from halogen, —CN, —OH, —NH 2 , —NO 2 , —C(O)OH, —C(S)OH, —C(O)NH 2 , —C(S)NH 2 , —S(O) 2 NH 2 , —NHC(O)NH 2 , —NHC(S)NH 2 , —NHS(O) 2 NH 2 , —C(NH)NH 2 , —CH═C(R k )(R k ), —OR k , —SR k , —OC(O)R k , —OC(S)R k , —P(═O)HR k , —P(═O)R k R k , —PH(═O)OR k , —P(═O)(OR k ) 2 , —OP(═O)(OR k ) 2 , —C(O)H, —O(CO)OR k , —C(O)R k , —C(S)R k , —C(O)OR k , —C(S)OR k , —S(O)R k , —S(O) 2 R k , —C(O)NHR k , —C(S)NHR k , —C(O)NR k R k , —C(S)NR k R k , —S(O) 2 NHR k , —S(O) 2 NR k R k , —C(NH)N HR k , —C(NH)NR k R k , —NHC(O)R k , —NHC(S)R k , —NR k C(O)R k , —NR k C(S)R k , —NHS(O) 2 R k , —NR k S(O) 2 R k , —NHC(O)NHR k , —NHC(S)NHR k , —NR k C(O)NH 2 , —NR k C(S)NH 2 , —NR k C(O)NHR k , —NR k C(S)NHR k , —NHC(O)NR k R k , —NHC(S)NR k R k , —NR k C(O)NR k R k , —NR k C(S)NR k R k , —NHS(O) 2 NHR k , —NR k S(O) 2 NH 2 , —NR k S(O) 2 NHR k , —NHS(O) 2 NR k R k , —NR k S(O) 2 NR k R k , —NHR k or —NR k R k ;

each R k is independently H, C 1-6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl or cycloalkylalkyl; or

two R k groups when attached to the same carbon or nitrogen atom are taken together to form a 3- to 6-membered carbocyclic ring or 3- to 8-membered heterocyclic ring having from 1-2 heteroatoms as ring members selected from O, N or S, wherein the nitrogen or sulfur ring atoms are optionally oxidized;

R 3 is H, halogen, —CN, optionally substituted C 1-6 alkyl, optionally substituted deuterated C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl-C 1-4 alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-C 1-4 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 3-8 cycloalkyl-C 1-4 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heterocycloalkyl-C 1-4 alkyl; and

R 5 is

optionally substituted with from 1 to 2 R 11 groups independently selected from D, halogen, C 1-6 alkyl, C 1-4 haloalkyl, C 1-4 haloalkoxy or —CN;

wherein the wavy line indicates the point of attachment to the rest of molecule.

2. The compound of claim 1 , wherein R 3 is halogen, —CN, optionally substituted C 1-6 alkyl, optionally substituted aryl, optionally substituted aryl-C 1-4 alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-C 1-4 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 3-8 cycloalkyl-C 1-4 alkyl, optionally substituted heterocycloalkyl, or optionally substituted heterocycloalkyl-C 1-4 alkyl.

3. The compound of claim 1 , wherein R 3 is deuterated C 1-6 alkyl, C 1-6 alkyl, aryl, heteroaryl, C 3-8 cycloalkyl, or heterocycloalkyl, wherein each R 3 is optionally substituted with from 1-3 substituents independently selected from CN, —OH, —NH 2 , —NO 2 , —C(O)OH, —C(S)OH, —C(O)NH 2 , —C(S)NH 2 , —S(O) 2 NH 2 , —NHC(O)NH 2 , —NHC(S)NH 2 , —NHS(O) 2 NH 2 , —C(NH)NH 2 , —B(OH) 2 , —Si(R n ) 3 , —CH═C(R n )(R n ), —OR n , —OC(O)R n , —OC(S)R n , —P(═O)R n R n , —P(═O)R n R n , —PH(═O)OR n , —P(═O)(OR n ) 2 , —OP(═O)(OR n ) 2 , —C(O)H, —O(CO)OR n , —C(O)R n , —C(S)R n , —C(O)OR n , —C(S)OR n , —S(O)R n , —S(O) 2 R n , —C(O)NHR n , —C(S)NHR n , —C(O)NR n R n , —C(S)NR n R n , —S(O) 2 NHR n , —S(O) 2 NHR n , —C(NH) NHR n , —C(NH)NR n R n , —NHC(O)R n , —NHC(S)R n , —NR n C(O)R n , —NR n C(S)R n , —NHS(O) 2 R n , —NR n S(O) 2 R n , —NHC(O)NHR n , —NHC(S)NHR n , —NR n C(O)NH 2 , —NR n C(S)NH 2 , —NR n C(O)NHR n , —N R n C(S)NHR n , —NHC(O)NR n R n , —NHC(S)NR n R n , —NR n C(O)NR n R n , —NR n C(S)NR n R n , —NHS(O) 2 NH R n , —NR n S(O) 2 NH 2 , —NR n S(O) 2 NHR n , —NHS(O) 2 NR n R n , —NR n S(O) 2 NR n R n , —NHR n , R n or —NR n R n , wherein each R n is independently selected from H, C 1-6 alkyl or aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl or cycloalkylalkyl; or two R n groups when attached to the same carbon or nitrogen atom are taken together to form a 3- to 6-membered carbocyclic ring or 3- to 8-membered heterocyclic ring having from 1-2 heteroatoms as ring members selected from O, N or S, wherein the nitrogen or sulfur ring atoms are optionally oxidized.

4. The compound of claim 1 , wherein R 3 is aryl or heteroaryl, wherein each R 3 is optionally substituted with from 1-3 substituents independently selected from halogen, vinyl, C 1-6 alkyl, —OH, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, —CN, —NH 2 , —NH(C 1-6 alkyl), —N(C 1-6 alkyl) 2 , C 3-6 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.

5. The compound of claim 1 , wherein R 3 is aryl or heteroaryl, each of which is optionally substituted with from 1-5 substituents independently selected from halogen, —CN, —OH, —NH 2 , —NO 2 , —CH═C(R i )(R i ), —C(O)OH, —C(S)OH, —C(O)NH 2 , —C(S)NH 2 , —S(O) 2 NH 2 , —NHC(O)NH 2 , —NHC(S)NH 2 , —NHS(O) 2 NH 2 , —C(NH)NH 2 , —OR i , —SR i , —OC(O)R i , —OC(S)R i , —P(═O)HR i , —P(═O)R i R i , —PH(═O)OR i , —P(═)(OR i ) 2 , —OP(═O)(OR i ) 2 , —C(O)H, —O(CO)OR i , —C(O)R i , —C(S)R i , —C(O)OR i , —C(S)OR i , —S(O)R i , —S(O) 2 R i , —C(O)NHR i , —C(S)NHR i , —C(O)NR i R i , —C(S)NR i R i , —S(O) 2 NHR i , —S(O) 2 NR i R i , —C(NH)NHR i , —C(NH)NR i R i , —NH C(O)R i , —NHC(S)R i , —NR i C(O)R i , —NR i C(S)R i , —NHS(O) 2 R i , —NR i S(O) 2 R i , —NHC(O)NHR i , —NHC(S) NHR i , —NR i C(O)NH 2 , —NR i C(S)NH 2 , —NR i C(O)NHR i , —NR i C(S)NHR i , —NHC(O)NR i R i , —NHC(S)N R i R i , —NR i C(O)NR i R i , —NR i C(S)NR i R i , —NHS(O) 2 NHR i , —NR i S(O) 2 NH 2 , —NR i S(O) 2 NHR i , —NHS(O) 2 NR i R i , —NR i S(O) 2 NR i R i , R i , —NHR i or —NR i R i , wherein each R i is independently C 1-6 alkyl, aryl, aryl-C 1-2 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkyl, heteroaryl, heteroaryl-C 1-4 alkyl, heterocycloalkyl or heterocycloalkyl-C 1-4 alkyl, wherein each R i is further optionally substituted with from 1-3 R p groups independently selected from halogen, CN, —OH, —NH 2 , —N(R q )(R q ), —NO 2 , —C(O)OH, —C(O)NH 2 , —S(O) 2 NH 2 , —NHC(O)NH 2 , —C(NH)NH 2 , —P(═O)HR q , —P(═O)R q R q , —PH(═O)OR q , —P(═O)(OR q ) 2 , —OP(═O)(OR q ) 2 , —OC(O)R q , —OC(S)R q , —C(O)R q , —C(S)R q , —C(O)OR q , —S(O) 2 R q , —C(O)NHR q , C 1-6 alkyl, C 1-6 alkoxy, halogen, C 1-6 haloalkyl or C 1-6 haloalkoxy, and wherein R q is C 1-6 alkyl.

6. The compound of claim 1 , wherein R 7 is H, D, C 1-6 alkyl, or deuterated C 1-6 alkyl.

7. The compound of claim 1 , wherein R 11 is halogen, CH 3 , CD 3 , CF 3 , CHF 2 , CH 2 F, CH 2 Cl or —CN.

8. The compound of claim 1 , wherein R 1 is 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-pyridazinyl, or 4-pyridazinyl.

9. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutical acceptable excipient or carrier.

10. A compound selected from:

or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof.

11. A compound selected from:

or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof.

12. A compound selected from:

or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof.

13. A pharmaceutical composition comprising a compound of claim 11 and a pharmaceutical acceptable excipient or carrier.

14. A compound of formula: