Antiviral compounds

Patent metadata

Field	Value
Publication number	US-11850247-B2
Application number	US-202117222433-A
Country	US
Kind code	B2
Filing date	Apr 5, 2021
Priority date	Apr 10, 2020
Publication date	Dec 26, 2023
Grant date	Dec 26, 2023

Abstract

The invention provides a compound of formula I, formula II, or formula III:

or a salt thereof, wherein R 1 -R 10 have any of the values described in the specification, as well as compositions comprising a compound of formula I. The compounds are useful as HIV-1 CA-targeting molecules and as antiviral agents.

First claim

What is claimed is:

1. A compound of formula I, formula II, or formula III:

or a salt thereof, wherein:
R 1 is selected from the group consisting of:

R 2 is methyl or ethyl;
R 3 is phenyl, optionally substituted at the 3-position with bromo, chloro, fluoro, methyl, or methoxy, and optionally substituted at the 4-position with bromo, chloro, fluoro, methyl, or methoxy;
R 4 is 4-chloropyridyl, 4-bromopyridyl, or phenyl that is optionally substituted at the 4-position with halo, methyl, ethyl, or methoxy;
R 5 is selected from the group consisting of:

R 6 is a ring:

which ring is optionally substituted with carboxy, (C 1 -C 6 )alkoxycarbonyl, or —C(═O)NR c R d ;
R 7 is 4-chloropyridyl, 4-bromopyridyl, or phenyl that is optionally substituted at the 4-position with halo, methyl, ethyl, or methoxy;
R 8 is selected from the group consisting of:

R 9 is pyridyl that is substituted with phenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, or 4-cyanophenyl or R 9 is imidazole that is substituted with phenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, or 4-cyanophenyl;
R 10 is 4-chloropyridyl, 4-bromopyridyl, or phenyl that is optionally substituted at the 4-position with halo, methyl, ethyl, or methoxy;
R a is H or methyl;
R b is phenyl that is optionally substituted with one or more groups independently selected from the group consisting of nitro, halo, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, hydroxy, —SO 2 F, and NR e R f ;
R c is H, phenyl, benzyl, or (C 1 -C 6 )alkyl;
R d is H, phenyl, benzyl, or (C 1 -C 6 )alkyl;
R e is H, hydroxy, or (C 1 -C 6 )alkyl;
R f is H or (C 1 -C 6 )alkyl;
R g is H, OH, or (C 1 -C 6 )alkoxy; and
R h is H or (C 1 -C 6 )alkyl.

2. The compound or salt of claim 1 , which is a compound of formula I or a salt thereof.

3. The compound or salt of claim 1 , which is a compound of formula II or a salt thereof.

4. The compound or salt of claim 1 , which is a compound of formula III or a salt thereof.

5. The compound or salt of claim 1 , which is a compound of formula Ia:

or a salt thereof.

6. The compound or salt of claim 1 , which is a compound of formula Ib:

or a salt thereof.

7. The compound or salt of claim 1 , which is a compound of formula Ic:

or a salt thereof.

8. The compound or salt of claim 1 , which is a compound of formula Ie:

or a salt thereof.

9. The compound or salt of claim 1 , which is a compound of formula Ig:

or a salt thereof.

10. The compound or salt of claim 1 , which is a compound of formula Ih:

or a salt thereof.

11. The compound or salt of claim 1 , which is a compound of formula

or a salt thereof.

12. The compound or salt of claim 1 , which is a compound of formula In:

or a salt thereof.

13. The compound or salt of claim 1 , which is a compound of formula (II), wherein R 6 is:

wherein R x is carboxy, (C 1 -C 6 )alkoxycarbonyl, or —C(═O)NR e R d ; or a salt thereof.

14. The compound or salt of claim 1 , which is a compound of formula (II), wherein R 6 is:

wherein R x is —C(═O)NR e R d ; or a salt thereof.

15. The compound or salt of claim 1 , which is a compound of formula IIIa:

or a salt thereof, wherein R y is phenyl.

16. The compound or salt of claim 1 , which is a compound of formula IIIb

or a salt thereof, wherein R z is phenyl or 4-cyanophenyl.

17. A pharmaceutical composition comprising a compound as described in claim 1 and a pharmaceutically acceptable excipient.

18. The pharmaceutical composition of claim 17 , that further comprises, a cytochrome P450 inhibitor.

19. The compound:

20. A pharmaceutical composition comprising: 1) a compound as described in claim 19 , 2) a pharmaceutically acceptable excipient, and optionally, 3) a cytochrome P450 inhibitor.

Assignees

• Univ Minnesota
• Univ Emory

Inventors

• Wang Zhengqiang
• Sarafianos Stefanos G

Classifications

• A61K31/517 Primary

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• A61K31/405

  Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin · CPC title

• A61K31/4178

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title

• A61K31/4184

  condensed with carbocyclic rings, e.g. benzimidazoles · CPC title