Preparation of oxime dual NK(1)/NK(2) antagonists with reduced NK(3) affinity.
By employing a stereosimplification approach, a thorough SAR exploration of the piperidine region of Sch 206272 was possible through a practical and efficient synthesis of substituted cyclic ureas. This SAR study led to the identification of a benzimidazolinone series of compounds which display single digit nanomolar NK(1)/NK(2) affinity and near micromolar binding for the NK(3) receptor.
Reichard
Gregory A
GA
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. gregory.reichard@spcorp.com
Grice
Cheryl A
CA
Shih
Neng-Yang
NY
Spitler
James
J
Majmundar
Sapna
S
Wang
Steven D
SD
Paliwal
Sunil
S
Anthes
John C
JC
Piwinski
John J
JJ
D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010091:Oximes / Q000737:chemistry* / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D064729:Neurokinin-1 Receptor Antagonists; D010091:Oximes; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin