Substituted pyrroline kinase inhibitors

• US 20090093634A1
• Filed: 09/22/2008
• Published: 04/09/2009
• Est. Priority Date: 03/27/2003
• Status: Abandoned Application

• Current Assignee: Bruce E. Maryanoff, Han-Cheng Zhang, Hong Ye
• Original Assignee: Bruce E. Maryanoff, Han-Cheng Zhang, Hong Ye
• Inventors: Ye, Hong, Zhang, Han-Cheng, Maryanoff, Bruce E.
• Application Number:
  US12/284,371
• Publication Number:
  US 20090093634A1
• Time in Patent Office: Days
• US Class Current: 546/113
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems

Abstract

The present invention is directed to novel substituted pyrroline compounds useful as kinase or dual-kinase inhibitors and methods for treating or ameliorating a kinase or dual-kinase mediated disorder.

Claims

1. A compound of Formula (I):

2. The compound of claim 1 wherein R is selected from the group consisting of R_a, -C_1-4alkyl-R_a, -C_2-4alkenyl-R_a, -C_2-4alkynyl-R_a and cyano.

3. The compound of claim 1 wherein R_a is selected from the group consisting of heterocyclyl, aryl and heteroaryl.

4. The compound of claim 1 wherein R_a is selected from the group consisting of dihydro-pyranyl, phenyl, naphthyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, pyridinyl, azaindolyl, indazolyl, benzofuryl, benzothienyl, dibenzofuryl and dibenzothienyl.

5. The compound of claim 1 wherein R¹ is -heteroaryl-R⁶;

wherein heteroaryl is attached to the azaindole nitrogen atom in the one position via a heteroaryl ring carbon atom.

6. The compound of claim 1 wherein R⁵ is 1 to 2-heteroaryl-R⁶.

7. The compound of claim 1 wherein R⁵ is 1 to 2 substituents independently selected from the group consisting of -imidazolyl-R⁶, -triazolyl-R⁶ and -tetrazolyl-R⁶.

8. The compound of claim 1 wherein R⁶ is 1 to 4-(C_1-4)alkyl-heteroaryl-R⁸;

with the proviso that, when R⁶ is attached to a carbon atom, R⁶ is -heteroaryl-R⁸.

9. The compound of claim 1 wherein R⁷ is 2 substituents independently selected from the group consisting of -(C_1-4)alkyl-heterocyclyl-R⁸ and -(C_1-4)alkyl-heteroaryl-R⁸.

10. The compound of claim 1 wherein R⁸ is 1 to 4 substituents attached to a carbon or nitrogen atom independently selected from the group consisting of hydrogen, -C_1-4alkyl, -(C_1-4)alkyl-(halo)_1-3 and -(C_1-4)alkyl-OH;

with the proviso that, when R⁸ is attached to a carbon atom, R⁸ is further selected from the group consisting of -C_1-4alkoxy, —

NH₂, —

NH(C_1-4alkyl), —

N(C_1-4alkyl)₂, cyano, halo, -(C_1-4)alkoxy-(halo)_1-3, hydroxy and nitro.

11. The compound of claim 1 wherein R⁹ is 1 to 2 substituents independently selected from the group consisting of hydrogen, -C_1-4alkoxy, —

NH₂, —

NH(C_1-4alkyl), —

N(C_1-4alkyl)₂, cyano, (halo)_1-3, hydroxy and nitro.

12. The compound of claim 1 wherein R² is -heteroaryl-R⁶.

13. The compound of claim 1 wherein R⁴ is 1 to 4 substituents attached to a carbon atom independently selected from the group consisting of -heterocyclyl and -heteroaryl.

14. The compound of claim 1 wherein R¹⁰ is 1 to 2 substituents independently selected from the group consisting of hydrogen, —

NH₂, —

NH(C_1-4alkyl), —

N(C_1-4alkyl)₂, cyano, (halo)_1-3, hydroxy, nitro and oxo.

15. The compound of claim 1 wherein R¹⁰ is 1 to 2 substituents independently selected from the group consisting of hydrogen and (halo)_1-3.

16. The compound of claim 1 wherein R¹⁰ is 1 to 2 substituents independently selected from the group consisting of hydrogen and (fluoro)₃.

17. The compound of claim 1 wherein Y and Z are independently selected from the group consisting of O, S, (H,OH) and (H,H);

with the proviso that one of Y and Z is O and the other is selected from the group consisting of O, S, (H,OH) and (H,H).

18. The compound of claim 1 wherein Y and Z are independently selected from the group consisting of O and (H,H);

with the proviso that one of Y and Z is O, and the other is selected from the group consisting of O and (H,H).

19. The compound of claim 1 wherein Y and Z are independently selected from O.