AZA-SUBSTITUTED INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

• US 20190307776A1
• Filed: 06/28/2017
• Published: 10/10/2019
• Est. Priority Date: 06/30/2016
• Status: Abandoned Application

• Current Assignee: ViiV Healthcare UK Limited (GSK plc)
• Original Assignee: ViiV Healthcare UK No 5 Ltd (GSK plc)
• Inventors: CHEN, Jie, CHEN, Yan, REGUEIRO-REN, Alicia, SIT, Sing-Yuen, SWIDORSKI, Jacob
• Application Number:
  US16/308,016
• Publication Number:
  US 20190307776A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/5365 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 217/06 with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 223/32 containing carbocyclic rings other than six-membered
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07J 71/0047 at position 2(3)

Abstract

Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, aza-substituted triterpenoid compounds that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formula I:

These compounds are useful for the treatment of HIV and AIDS.

Claims

1. (canceled)

3-9. -9. (canceled)

11-17. -17. (canceled)

19-23. -23. (canceled)

25-27. -27. (canceled)

28. A compound of Formula II, or a pharmaceutically acceptable salt thereof:

2. A compound or salt as claimed in claim 28, wherein R₁ is isopropenyl.

10. A compound or salt as claimed in claim 28, wherein Y is —

COOH.

18. A compound or salt as claimed in claim 28, wherein W is —

CH₂OR₂.

24. A compound or salt as claimed in claim 28 wherein W is —

CH₂NR₂₆R₂₇.

30. A pharmaceutical composition comprising a compound or salt of claim 28 and a pharmaceutically acceptable carrier.

31. The composition of claim 30 further comprising a at least one other agent used for treatment of AIDS or HIV infection selected from nucleoside HIV reverse transcriptase inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, HIV protease inhibitors, HIV fusion inhibitors, HIV attachment inhibitors, CCR5 inhibitors, CXCR4 inhibitors, HIV budding or maturation inhibitors, and HIV integrase inhibitors, and a pharmaceutically acceptable carrier.

32. The composition of claim 30 wherein the other agent is dolutegravir.

33. A method for treating HIV infection comprising administering a compound of claim 28, or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

34. The method of claim 33 further comprising administering at least one other agent used for treatment of AIDS or HIV infection selected from nucleoside HIV reverse transcriptase inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, HIV protease inhibitors, HIV fusion inhibitors, HIV attachment inhibitors, CCR5 inhibitors, CXCR4 inhibitors, HIV budding or maturation inhibitors, and HIV integrase inhibitors.

35. The method of claim 34 wherein the other agent is dolutegravir.

36. The method of claim 34 wherein the other agent is administered to the patient prior to, simultaneously with, or subsequently to the compound or salt of claim 28.

29. (canceled)