Heterocyclic compounds and uses thereof

• US 9,315,505 B2
• Filed: 06/11/2014
• Issued: 04/19/2016
• Est. Priority Date: 05/07/2009
• Status: Active Grant

• Current Assignee: Intellikine, Inc.
• Original Assignee: Intellikine, Inc.
• Inventors: Ren, Pingda, Liu, Yi, Li, Liansheng, Wilson, Troy Edward
• Primary Examiner(s): Shameem, Golam M M
• Assistant Examiner(s): DANIEL, LAURA M
• Application Number:
  US14/302,340
• Publication Number:
  US 20140296207A1
• Time in Patent Office: 678 Days
• US Class Current: 1/1
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/08 of the prostate
• 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 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 473/34 : attached in position 6, e.g. adenine
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems

Abstract

Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the isoquinolone entities, and methods of using these chemical entities for treating diseases and conditions associated with P13 kinase activity are described herein.

Claims

1. A compound of Formula I-A or Formula I-B:

2. The compound of claim 1 wherein

W¹ is N, W² is CR⁶, W³ is CR⁷, W⁴ is CR⁸;

W¹ is CR⁵, W² is N, W³ is CR⁷, W⁴ is CR⁸;

W¹ is CR⁵, W² is CR⁶, W³ is N, W⁴ is CR⁸;

W¹ is N, W² is CR⁶, W³ is N, W⁴ is CR⁸;

W¹ is N, W² is N, W³ is CR⁷, W⁴ is CR⁸;

W¹ is N, W² is CR⁶, W³ is CR⁷, W⁴ is N;

W¹ is CR⁵, W² is N, W³ is N, W⁴ is CR⁸;

W¹ is CR⁵, W² is N, W³ is CR⁷, W⁴ is N;

W¹ is CR⁵, W² is CR⁶, W³ is N, W⁴ is N;

or

W¹ is CR⁵, W² is CR⁶, W³ is CR⁷, W⁴ is CR⁸.

3. The compound of claim 2 wherein the compound of Formula I-A is a compound of Formula XV-A or the compound of Formula I-B is a compound of Formula XV-B:

4. The compound of claim 1 wherein n is 0 and R^1′

is hydrogen, amino, alkoxy, alkyl, heterocycloalkyl, aryl, or NR′

R″

wherein R′ and

R″

are taken together with nitrogen to form a cyclic moiety.

5. The compound of claim 1 wherein n is 1 and R^1′

is amino, alkoxy, alkyl, or NR′

R″

wherein R′ and

R″

are taken together with nitrogen to form a cyclic moiety.

6. The compound of claim 5 wherein n is 1 and R^1′

is alkyl which is substituted with heterocycloalkyl or R^1′

is NR′

R″

wherein R′ and

R″

are taken together with nitrogen to form a cyclic moiety.

7. The compound of claim 1 wherein R⁸ is hydrogen, alkyl,halo.

8. The compound of claim 7 wherein R⁸ is alkyl substituted with one or more fluoro.

9. The compound of claim 1 wherein X is —

CH₂—

,—

CH(CH₃)—

, —

CH(C₆H₅)—

or —

CH(CH₂CH₃)—

.

10. The compound of claim 1 wherein Y is absent, —

O—

, —

N(R⁹)—

, —

N(R⁹)C(R¹⁰)₂—

, or —

S(═

O)₂—

.

11. The compound of claim 1 wherein W_d is:

12. The compound of claim 11 wherein R¹¹ is amino.

13. The compound of claim 11 wherein R¹² is a monocyclic heteroaryl, a bicyclic heteroaryl, or a heterocycloalkyl.

14. The compound of claim 1 having a structure of Formula XVI-A:

15. The compound of claim 12 having a structure of Formula XVIII-A:

16. A composition comprising a pharmaceutically acceptable excipient and a compound of claim 1.

17. The composition of claim 16 wherein the composition is a liquid, solid, semi-solid, gel, or an aerosol form.

18. The compound of claim 1, wherein the compound is: