HETEROCYCLIC COMPOUND HAVING INHIBITORY ACTIVITY ON PI3K

• US 20110105457A1
• Filed: 04/16/2009
• Published: 05/05/2011
• Est. Priority Date: 04/18/2008
• Status: Abandoned Application

• Current Assignee: Shionogi & Co., Ltd.
• Original Assignee: Shionogi & Co., Ltd.
• Inventors: Okamoto, Kazuya, Kano, Kazuya, Mitsuoka, Yasunori, Taniyama, Daisuke, Fujioka, Masahiko
• Application Number:
  US12/988,129
• Publication Number:
  US 20110105457A1
• Time in Patent Office: Days
• US Class Current: 514/210.02
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/16 Otologicals
• 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 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 487/04 : Ortho-condensed systems

Abstract

The purpose of the present invention is to provide a compound or a pharmaceutically acceptable salt thereof which inhibits the activity of PI3K to regulate many biological processes including the growth, differentiation, survival, proliferation, migration, metabolism, and the like of cells and is therefore useful for the prevention/treatment of diseases including inflammatory diseases, arteriosclerosis, vascular/circulatory diseases, cancer/tumors, immune system diseases, cell proliferative diseases, infectious diseases, and the like. This was achieved by providing a substituted 2-amino-5,6-nitrogenated fused ring compound shown in the present specification, or a pharmaceutically acceptable salt thereof.

Claims

1. A pharmaceutical composition comprising a compound of the formula (I):

2. The pharmaceutical composition according to claim 1, comprising a compound of formula (II):

19. A method for treating a phosphatidylinositol-3-kinase dependent disease in a human, comprising the step of administering to said human the pharmaceutical composition according to claim 1 or claim 2.

21. A method for preventing or treating inflammation in a human, comprising the step of administering to said human the pharmaceutical composition according to claim 1 or claim 2.

3. A compound of formula (IV):

4. The compound according to claim 3 represented by formula (V):

5. The compound according to claim 4 wherein R¹⁶, R¹⁷, and R¹⁸ are each independently hydrogen;

a pharmaceutically acceptable salt thereof, or a solvate thereof.

6. The compound according to claim 3 wherein R¹² is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

a pharmaceutically acceptable salt thereof, or a solvate thereof.

7. The compound according to claim 3 wherein R¹² is substituted or unsubstituted aminocarbonyl;

a pharmaceutically acceptable salt thereof, or a solvate thereof.

8. The compound according to claim 3 wherein R¹³ is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

a pharmaceutically acceptable salt thereof, or a solvate thereof.

9. The compound according to claim 3 wherein R¹³ is substituted or unsubstituted aryloxy, substituted or unsubstituted arylthio, or substituted or unsubstituted arylamino;

a pharmaceutically acceptable salt thereof, or a solvate thereof.

10. The compound according to claim 3 wherein R¹³ is substituted or unsubstituted alkyloxycarbonyl, or substituted or unsubstituted aminocarbonyl;

a pharmaceutically acceptable salt thereof, or a solvate thereof.

11. The compound according to claim 3 wherein:

R¹² is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and

R¹³ is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

a pharmaceutically acceptable salt thereof, or a solvate thereof.

12. The compound according to claim 3 wherein:

R¹² is substituted or unsubstituted aminocarbonyl; and

R¹³ is substituted or unsubstituted acylamino, substituted or unsubstituted arylamino, substituted or unsubstituted heteroarylamino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted acyl, the formula;

—

OR¹⁴, or the formula;

—

S(O)_mR¹⁵;

wherein R¹⁴, R¹⁵ and m are as defined in claim 3;

a pharmaceutically acceptable salt thereof, or a solvate thereof.

13. A pharmaceutical composition comprising the compound, a pharmaceutically acceptable salt thereof, or a solvate thereof according to claim 3 or claim 4 as an active ingredient.

14. A method for treating a phosphatidylinositol-3-kinase dependent disease in a human, comprising the step of administering to said human the compound, a pharmaceutically acceptable salt thereof, or a solvate thereof, according to claim 3 or claim 4.

16. A method for preventing or treating inflammation in a human, comprising the step of administering to said human the compound, a pharmaceutically acceptable salt thereof, or a solvate thereof, according to claim 3 or claim 4.

20. A method for treating a phosphatidylinositol-3-kinase dependent disease in a human, comprising the step of administering to said human the pharmaceutical composition according to claim 13.

22. A method for preventing or treating inflammation in a human, comprising the step of administering to said human the pharmaceutical composition according to claim 13.

15. (canceled)

17-18. -18. (canceled)