Modulators of chemokine receptors

Patent metadata

Field	Value
Publication number	US-10988464-B2
Application number	US-201916414272-A
Country	US
Kind code	B2
Filing date	May 16, 2019
Priority date	Nov 19, 2015
Publication date	Apr 27, 2021
Grant date	Apr 27, 2021

Abstract

Compounds are provided as chemokine inhibitors having the structure:

First claim

What is claimed is:

1. A compound having a formula selected from the group consisting of

2. The compound of claim 1 , having the formula

3. The compound of claim 1 , having the formula

4. The compound of claim 1 , having the formula

5. A pharmaceutical composition comprising a compound of formula (A1)

or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or dilutent wherein
R 1a is selected from CH 3 and Cl;
R 1b is H or is CH 3 ;
R 3 is H or D;
R 4 is H, C 1-8 alkyl, OH, —NR a R, —C 1-4 alkoxy, and Y; wherein the C 1-8 alkyl is optionally substituted with halogen, —CN, —CO 2 R a , —CONR a R b , —C(O)R a , OC(O)NR a R b , —NR a C(O)R b , —NR a C(O) 2 R c , —NR a C(O)NR a R b , —NR a R b , —OR a , —S(O) 2 NR a R b , —NR a S(O) 2 R b and Y, wherein Y is a 4 to 8 membered cycloheteroalkyl group or a 3 to 8 membered cycloalkyl group or a 5- or 6-membered aryl or heteroaryl group any of which is optionally substituted with from 1 to four substituents selected from halogen, oxo, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —C 1-6 hydroxyalkyl, —C 1-6 haloalkyl, O—C 1-6 haloalkyl, —C 1-4 alkyl-O—C 1-4 alkyl, —C 1-6 alkyl-NR a R b , —C 1-6 alkyl-CO 2 H, —C 1-6 alkyl-CO 2 R a , —C 1-6 alkyl-CONR a R b , —C 1-6 alkyl-C(O)R a , —C 1-6 alkyl-OC(O)NR a R b , —C 1-6 alkyl-NR a C(O)R b , —C 1-6 alkyl-NR a C(O) 2 R c , —C 1-6 alkyl-NR a C(O)NR a R b , —C 1-6 alkyl-OR a , —C 1-6 alkyl-S(O) 2 NR a R b , —C 1-6 alkyl-NR a S(O) 2 R b , —CO 2 R a , —CONR a R b , —C(O)R a , —OC(O)NR a R b , —NR a C(O)R b , —NR a C(O) 2 R c , —NR a C(O)NR a R b , —NR a R b , —OR a ,—S(O) 2 NR a R b , —NR a S(O) 2 R b , —CH 2 CO 2 R a ; each R a and R b is independently selected from hydrogen, C 1-4 alkyl, C 1-4 hydroxyalkyl and C 1-4 haloalkyl, and R c is selected from C 1-4 alkyl, C 1-4 hydroxyalkyl and C 1-4 haloalkyl; and wherein the 4 to 8 membered cycloheteroalkyl group and the 3 to 8 membered cycloalkyl group may additionally be optionally substituted with oxo;
R 5a and R 5b are each independently selected from H, F, Cl, Br and CH 3 ;
R 6a and R 6b are each members independently selected from the group consisting of H, C 1-4 alkyl, C 1-4 hydroxyalkyl and C 1-4 haloalkyl; or optionally R 6a and R 6b are taken together to form oxo (═O) or a 4 to 6 membered cycloheteroalkyl group or a 3 to 6 membered cycloalkyl group; and
R 7 is methyl or ethyl.

6. The pharmaceutical composition of claim 5 , wherein R 4 is H or Y; and R 6a and R 6b are each independently selected from H and CH 3 or a pharmaceutically acceptable salt thereof.

7. The pharmaceutical composition of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 1a is CH 3 ; R 1b is H or is CH 3 ; R 3 is H or D; R 4 is H; R 5a is H, F, Me or Cl or Br; R 5b is H or F; R 6a and R 6b are each H; and R 7 is methyl or ethyl; or a pharmaceutically acceptable salt thereof.

8. The pharmaceutical composition of claim 5 , or a pharmaceutically acceptable salt thereof, wherein said compound is substantially free of other isomers at the carbon atom bearing R 3 .

9. The pharmaceutical composition of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 4 is Y.

10. The pharmaceutical composition of claim 5 , wherein said compound has a formula selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

11. The pharmaceutical composition of claim 10 , wherein said compound has the formula

or a pharmaceutically acceptable salt thereof.

12. The pharmaceutical composition of claim 10 , wherein said compound has the formula

or a pharmaceutically acceptable salt thereof.

13. The pharmaceutical composition of claim 10 , wherein said compound has the formula

or a pharmaceutically acceptable salt thereof.

14. The pharmaceutical composition of claim 10 , wherein said compound has the formula

or a pharmaceutically acceptable salt thereof.

15. The pharmaceutical composition of claim 10 , wherein said compound has the formula

or a pharmaceutically acceptable salt thereof.

16. The pharmaceutical composition of claim 10 , wherein said compound has the formula

or a pharmaceutically acceptable salt thereof.

Assignees

• Chemocentryx Inc

Inventors

• Chen Xi
• Dragoli Dean R
• Fan Junfa
• Kalisiak Jaroslaw
• Krasinski Antoni
• Leleti Manmohan Reddy
• Mali Venkat
• Mcmahon Jeffrey
• Singh Rajinder
• Tanaka Hiroko
• Yang Ju
• Yu Chao
• Zhang Penglie

Classifications

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D405/14 Primary

  containing three or more hetero rings · CPC title

• C07D405/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D209/46

  with an oxygen atom in position 1 · CPC title