Inhibitors of human immunodeficiency virus replication

Patent metadata

Field	Value
Publication number	US-10035760-B2
Application number	US-201415031352-A
Country	US
Kind code	B2
Filing date	Oct 23, 2014
Priority date	Oct 24, 2013
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

Abstract

Compounds of Formula I with activity against HIV, including pharmaceutical compositions and methods for using these compounds in treating human immunodeficiency virus (HIV) infection, are set forth:

First claim

What is claimed is:

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof:

wherein:
R 1 is alkyl, aryl, arylalkyl, cycloalkyl or heteroaryl; wherein said aryl, arylalkyl or heteroaryl moieties are linked to the parent molecule through their respective carbon atoms, and further wherein said aryl, arylalkyl or heteroaryl moieties are substituted with 0-4 groups independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkoxycarbonylamino, alkyl, alkylsulphonyl, alkylthioxy, aminocarbonyl, alkynyl, carboxylic acid, cyano, halo, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, thioxy, —SO 2 alkyl, heteroaryl, and nitro;
R 2 is —H, C 1 -C 4 alkyl or C 3 -C 4 cycloalkyl;
or R 1 and R 2 together with the atoms to which they are attached form a heterocyclic ring optionally substituted with 0-2 alkyl groups;
R 3 is —H, C 1 -C 4 alkyl or C 3 -C 4 cycloalkyl;
R 4 is aryl which is substituted with 0-3 groups independently selected from the group consisting of alkenoxy, alkenyl, alkoxy, alkoxycarbonyl, alkyl, benzyloxy, carboamide, cyano, halo, haloalkyl, haloalkoxy, —NHCO(alkyl), —SO 2 NH-heterocycle, —OH, nitro, and —CH 2 OH;
R 5 and R 6 are independently selected from H or alkyl, or R 5 and R 4 together with the atom to which they are attached form an aryl group, or R 5 and R 6 together with the atoms to which they are attached form a C 3 -C 4 cycloalkyl;
R 7 is alkyl, aryl, heteroaryl, C 3 -C 7 cycloalkyl or dialkylaminoalkyl, wherein said aryl or heteroaryl is substituted with 0-3 groups independently selected from the group consisting of —OH, —NHCOalkyl, —NHCON(alkyl) 2 , —NHCO 2 -alkyl, —CONH 2 , —CN, —SO 2 N(alkyl) 2 , alkoxy, alkyl, halo, haloalkoxy, and haloalkyl; and
R 8 is alkyl containing 1-6 carbon atoms, or C 3 -C 4 cycloalkyl;
or R 7 and R 8 together with the nitrogen atom to which they are attached form a heterocycle which is substituted with 0-3 groups independently selected from the group consisting of alkyl, alkoxy, halo, —OH, —CN, and —SO 2 N(alkyl) 2 .

2. A compound or salt of claim 1 , wherein R 1 is aryl.

3. A compound or salt of claim 2 , wherein R 1 is phenyl, biphenyl or naphthalenyl.

4. A compound of claim 1 , wherein R 1 is heteroaryl.

5. A compound of claim 4 , wherein R 1 is selected from the group of thiophene, pyrrazolophenyl, furanylphenyl, pyridinylphenyl, pyrimidinylphenyl, thiophenylphenyl, benzothiophene, oxadiazolephenyl, indole, and azaindole.

6. A compound of claim 1 , wherein R 1 and R 2 together with the —N—SO 2 moiety to which they are attached form a heterocyclic ring.

7. A compound of claim 6 , wherein said heterocyclic ring is isothiazolidine 1,1-dioxide.

8. A compound or salt of claim 1 , wherein R 4 is phenyl, naphthanenyl, or biaryl.

9. A compound of claim 1 , wherein R 7 is aryl.

10. A compound of claim 9 , wherein R 7 is phenyl or naphthalenyl.

11. A compound or salt of claim 1 , wherein R 7 is selected from the group of bezodioxolyl, dihalobezodioxolyl, benzothiazole, quinoline, benzothiazole, benzimidazole, quinazoline, quinoxaline, dihydrobenzofuran, chroman, benzoxazole, isoquinoline, and isoquinolinone.

12. A compound of claim 1 , wherein R 7 and R 8 together form a heterocycle which is selected from the group of tetrahydroisoquinoline, dihydro-benzo[1,4]oxazine, dihydroindole, tetrahydrothieno[3,2-c]pyridine, 2-oxa-5-azabicyclo[2.2.1]heptanes, azetidine, and pyridinylpyrrolidine.

13. A compound selected from the group consisting of:

Assignees

• Viiv Healthcare Uk No 5 Ltd

Inventors

• Pendri Annapurna
• Li Guo
• Bender John A
• Yang Zhong
• Wang Alan Xiangdong
• Beno Brett R
• Fridell Robert A
• Belema Makonen
• Meanwell Nicholas A
• Gentles Robert G

Classifications

• A61P31/18

  for HIV · CPC title

• C07D333/18

  by sulfur atoms · CPC title

• C07D317/66

  Nitrogen atoms not forming part of a nitro radical · CPC title

• C07D311/58

  other than with oxygen or sulphur atoms in position 2 or 4 · CPC title

• C07C311/58 Primary

  having nitrogen atoms of the sulfonylurea groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title