C5aR antagonists

Patent metadata

Field	Value
Publication number	US-10035768-B2
Application number	US-201715722819-A
Country	US
Kind code	B2
Filing date	Oct 2, 2017
Priority date	Jun 24, 2010
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

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 process for preparing a compound of formula (ii),

comprising
(a) treating a compound of formula (i)

with H 2 and a platinum oxide catalyst under reducing conditions; and

(b) subjecting the product of step (a) to resolution with di-toluoyl-L-tartaric acid to provide compound (ii).

2. A process in accordance with claim 1 , wherein compound (ii) is prepared in about 97% enantiomeric excess.

3. A process in accordance with claim 1 , further comprising a step wherein the compound of formula (i) is prepared by treating ethyl 2-chloronicotinate with N-Boc-4-aminophenylboronic acid in the presence of Pd(PPh 3 ) 4 .

4. A process in accordance with claim 1 , wherein step (a) is carried out in ethanol and HCl.

5. A process in accordance with claim 1 , wherein step (b) is carried out in THF and tert-butyl methyl ether.

6. A process for preparing a compound of formula (ii),

comprising subjecting a compound of formula (iia)

to resolution with di-toluoyl-L-tartaric acid to provide compound (ii).

7. A process in accordance with claim 6 , wherein compound (ii) is prepared in about 97% enantiomeric excess.

8. A compound having the formula:

9. A compound of claim 8 , having the formula:

which is provided in about 97% enantiomeric excess.

10. A compound having the formula:

Assignees

• Chemocentryx Inc

Inventors

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

Classifications

• A61P43/00

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

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title