C5aR antagonists

Patent metadata

Field	Value
Publication number	US-10660897-B2
Application number	US-201816030729-A
Country	US
Kind code	B2
Filing date	Jul 9, 2018
Priority date	Dec 22, 2008
Publication date	May 26, 2020
Grant date	May 26, 2020

Abstract

Compounds are provided that are modulators of the C5a receptor. The compounds are substituted piperidines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activation of C5a receptors.

First claim

What is claimed is:

1. A method for treating a human suffering from a disease or disorder selected from the group consisting of tissue graft rejection, hyperacute rejection of transplanted organs, rheumatoid arthritis, lupus nephritis, and autoimmune hemolytic and thrombocytopenic states, comprising administering to the human an effective amount of a compound having the formula:

and pharmaceutically acceptable salts, hydrates and rotomers thereof; wherein
X 1 is selected from the group consisting of N, CH and CR 1 ;
each R 1 is independently selected from the group consisting of
halogen, —CN, —R c , —CO 2 R a , —CONR a R b , and —C(O)R a ; wherein each R a and R b is independently selected from hydrogen, C 1-8 alkyl, and C 1-8 haloalkyl, each R c is independently selected from the group consisting of C 1-8 alkyl, C 1-8 haloalkyl, and C 3-6 cycloalkyl;

the subscript n is an integer of from 0 to 2;
X 2 is selected from the group consisting of N, CH and CR 2 ;
each R 2 is independently selected from the group consisting of
halogen, —CN, —R f , —CO 2 R d , —CONR d R e , and —C(O)R d ; wherein each R d and R e is independently selected from hydrogen, C 1-8 alkyl, and C 1-8 haloalkyl; each R f is independently selected from the group consisting of C 1-8 alkyl, C 1-8 haloalkyl, and C 3-6 cycloalkyl;

the subscript m is an integer of from 0 to 2; and
C 3 is selected from the group consisting of:

2. The method of claim 1 , wherein the disease or disorder is lupus nephritis.

3. The method of claim 1 , wherein the disease or disorder is tissue graft rejection or hyperacute rejection of transplanted organs.

4. The method of claim 1 , wherein the disease or disorder is autoimmune hemolytic and thrombocytopenic states.

5. The method of claim 1 , wherein the disease or disorder is rheumatoid arthritis.

Assignees

• Chemocentryx Inc

Inventors

• Fan Pingchen
• Greenman Kevin Lloyd
• Leleti Manmohan Reddy
• Li Yandong
• Powers Jay
• Tanaka Hiroko
• Yang Ju
• Zeng Yibin

Classifications

• C07D405/10

  linked by a carbon chain containing aromatic rings · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title

• C07D401/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K31/451

  having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine · CPC title