Heterocyclic compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-9718847-B2
Application number	US-201414486986-A
Country	US
Kind code	B2
Filing date	Sep 15, 2014
Priority date	Mar 15, 2013
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

Abstract

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

First claim

What is claimed is:

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:

Assignees

• Plexxikon Inc

Inventors

• Zhang Jiazhong
• Buell John
• Chan Katrina
• Ibrahim Prabha N
• Lin Jack
• Pham Phuongly
• Shi Songyuan
• Spevak Wayne
• Wu Guoxian
• Wu Jeffrey

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/18

  for HIV · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title