Discovery and synthesis of 6,7,8,9-tetrahydro-5H-pyrimido-[4,5-d]azepines as novel TRPV1 antagonists.
Utilization of a tetrahydro-pyrimdoazepine core as a bioisosteric replacement for a piperazine-urea resulted in the discovery a novel series of potent antagonists of TRPV1. The tetrahydro-pyrimdoazepines have been identified as having good in vitro and in vivo potency and acceptable physical properties.
Johnson & Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121, USA. nhawrylu@its.jnj.com
Natalie A
NA
Hawryluk
Jeffrey E
JE
Merit
Alec D
AD
Lebsack
Bryan J
BJ
Branstetter
Michael D
MD
Hack
Nadia
N
Swanson
Hong
H
Ao
Michael P
MP
Maher
Anindya
A
Bhattacharya
Qi
Q
Wang
Jamie M
JM
Freedman
Brian P
BP
Scott
Alan D
AD
Wickenden
Sandra R
SR
Chaplan
J Guy
JG
Breitenbucher
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology; D055808:Drug Discovery; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
D001381:Azepines; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat