Heterocyclic tyrosine kinase inhibitors

Patent metadata

Field	Value
Publication number	US-9273028-B2
Application number	US-201113882449-A
Country	US
Kind code	B2
Filing date	Oct 28, 2011
Priority date	Oct 29, 2010
Publication date	Mar 1, 2016
Grant date	Mar 1, 2016

Abstract

The present invention provides compounds useful as inhibitors of Tec family kinases, compositions thereof, and methods of using the same.

First claim

What is claimed is:

1. A compound of formula IV:

or a pharmaceutically acceptable salt thereof;
wherein:
each of m and q is independently 0-5;
Ring A is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
R 2 is halogen, —NO 2 , —CN, —OR, —SR, —N(R) 2 , —C(O)R, —CO 2 R, —C(O)C(O)R, —C(O)CH 2 C(O)R, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —SO 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)N(R) 2 , —N(R)C(═NR)N(R) 2 , —C(═NR)N(R) 2 , —C═NOR, —N(R)C(O)N(R) 2 , —N(R)SO 2 N(R) 2 , —N(R)SO 2 R, —OC(O)N(R) 2 , or an optionally substituted group selected from C 1-12 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-10 membered saturated or partially unsaturated bicyclic carbocyclic ring, a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered bicyclic aryl ring, a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
each R is independently hydrogen or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic ring, a 3-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:
two R groups on the same nitrogen are taken together with their intervening atoms to form an optionally substituted 3-7 membered saturated, partially unsaturated, or heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each R 3 and R 4 is independently halogen, —NO 2 , —CN, —OR, —SR, —N(R) 2 , —C(O)R, —CO 2 R, —C(O)C(O)R, —C(O)CH 2 C(O)R, —S(O)R, —S(O) 2 R, —C(O)N(R) 2 , —SO 2 N(R) 2 , —OC(O)R, —N(R)C(O)R, —N(R)N(R) 2 , —N(R)C(═NR)N(R) 2 , —C(═NR)N(R) 2 , —C═NOR, —N(R)C(O)N(R) 2 , —N(R)SO 2 N(R) 2 , —N(R)SO 2 R, —OC(O)N(R) 2 , or an optionally substituted group selected from C 1-12 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-10 membered saturated or partially unsaturated bicyclic carbocyclic ring, a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered bicyclic aryl ring, a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

2. The compound of claim 1 , wherein Ring A is an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

3. The compound of claim 1 , wherein Ring A is an optionally substituted 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

4. A compound listed in Table 4 selected from any one of compounds 4, 5, 7, 11, 12, 17-34, 41, 51, 52, 58, 60-73, 75, 79-81, 89-92, 105, 226-228, or a pharmaceutically acceptable salt thereof.

5. The compound of claim 3 , wherein Ring A selected from:

wherein each Ring D is a 5 membered saturated, partially unsaturated, or aryl fused ring having 1-2 heteroatoms in addition to the nitrogen atom independently selected from nitrogen, oxygen, or sulfur.

6. The compound of claim 1 , wherein Ring A is selected from:

wherein X is halogen.

7. A pharmaceutical formulation comprising a compound of claim 1 and a pharmaceutically acceptable excipient.

8. A method of decreasing the enzymatic activity or a Tec kinase comprising contacting a Tec kinase with an effective amount of a compound of claim 1 or a composition thereof.

Assignees

• Hopkins Brian T
• Scott Daniel
• Conlon Patrick
• Jenkins Tracy J
• Powell Noel
• Guan Bing
• Cuervo Julio H
• Wang Deping
• Taveras Art
• Biogen Ma Inc
• Sunesis Pharmaceuticals Inc

Inventors

• Hopkins Brian T
• Scott Daniel
• Conlon Patrick
• Jenkins Tracy J
• Powell Noel
• Guan Bing
• Cuervo Julio H
• Wang Deping
• Taveras Art

Classifications

• C07D401/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/4545

  containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• C07D473/34

  attached in position 6, e.g. adenine · CPC title