Soluble C5aR antagonists

Patent metadata

Field	Value
Publication number	US-11254695-B2
Application number	US-201916660994-A
Country	US
Kind code	B2
Filing date	Oct 23, 2019
Priority date	Apr 4, 2016
Publication date	Feb 22, 2022
Grant date	Feb 22, 2022

Abstract

Compounds are provided to modulate the C5a receptor. The compounds have the following Formula (I):including stereoisomers and pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

First claim

What is claimed is:

1. A compound of Formula (I)

or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from the group consisting of —O—CH 2 —O—P(O)OR a OR b , —O—C(O)—C 1-6 alkylene-L 2 -X 1 , O—P(O)OR a OR b , and —O—C(O)-A 1 -(C 1-3 alkylene) n -C 4-7 heterocyclyl wherein the C 4-7 heterocyclyl is optionally substituted with 1 to 6 R c groups;
A 1 is selected from the group consisting of C 6-10 aryl, C 3-10 cycloalkyl, C 5-10 heteroaryl and C 5-10 heterocyclyl, each of which is optionally substituted with 1 to 5 R x which can be the same or different;
n=0 or 1;
L 2 is independently selected from the group consisting of a bond, —O—C(O)—C 1-6 alkylene-, and —NR d —C(O)—C 1-6 alkylene-;
X 1 is independently selected from the group consisting of —NR e R f , —P(O)OR a OR b , —O—P(O)OR a OR b , and —CO 2 H;
R 2 is H;
R 3 is H;
each R x is independently selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, CN, NR y R z , SR y and OR y ;
each R c is independently selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, CN, NR y R z , SR y and OR y ;
each R a , R b , R d , R e , R f , R y and R z is independently selected from the group consisting of H and C 1-6 alkyl.

2. The compound of claim 1 selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , which is in the form of a pharmaceutically acceptable salt.

4. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

5. The pharmaceutical composition of claim 4 , formulated for intravenous, transdermal or subcutaneous administration.

6. A compound of claim 1 , having the formula

or a pharmaceutically acceptable salt thereof.

7. A compound of claim 1 , having the formula

or a pharmaceutically acceptable salt thereof.

8. A compound of claim 1 , having the formula

or a pharmaceutically acceptable salt thereof.

9. A compound of claim 1 , having the formula

or a pharmaceutically acceptable salt thereof.

10. A compound of claim 1 , having the formula

or a pharmaceutically acceptable salt thereof.

11. A compound of claim 1 , having the formula

or a pharmaceutically acceptable salt thereof.

12. A compound of claim 1 , having the formula

or a pharmaceutically acceptable salt thereof.

13. A compound of claim 1 , having the formula

or a pharmaceutically acceptable salt thereof.

14. A compound of claim 1 , having the formula

or a pharmaceutically acceptable salt thereof.

15. A compound of claim 1 , having the formula

or a pharmaceutically acceptable salt thereof.

16. A compound of claim 1 , having the formula

or a pharmaceutically acceptable salt thereof.

Assignees

• Chemocentryx Inc

Inventors

• Fan Pingchen
• Krasinski Antoni
• Mali Venkat Reddy
• Miao Shichang
• Punna Sreenivas
• Song Yang
• Stella Valentino J
• Zeng Yibin
• Zhang Penglie

Classifications

• C07F9/65583 Primary

  each of the hetero rings containing nitrogen as ring hetero atom · CPC title

• C07F9/59

  Hydrogenated pyridine rings · CPC title

• C07D401/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D211/60 Primary

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title