Preparation of oxime dual NK(1)/NK(2) antagonists with reduced NK(3) affinity

Gregory A Reichard; Cheryl A Grice; Neng-Yang Shih; James Spitler; Sapna Majmundar; Steven D Wang; Sunil Paliwal; John C Anthes; John J Piwinski

doi:10.1016/s0960-894x(02)00462-6

Preparation of oxime dual NK(1)/NK(2) antagonists with reduced NK(3) affinity

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2355-8. doi: 10.1016/s0960-894x(02)00462-6.

Authors

Gregory A Reichard¹, Cheryl A Grice, Neng-Yang Shih, James Spitler, Sapna Majmundar, Steven D Wang, Sunil Paliwal, John C Anthes, John J Piwinski

Affiliation

¹ Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. gregory.reichard@spcorp.com

PMID: 12161132
DOI: 10.1016/s0960-894x(02)00462-6

Abstract

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.

MeSH terms

Benzimidazoles / chemistry
Benzimidazoles / pharmacology
Neurokinin-1 Receptor Antagonists
Oximes / chemistry*
Oximes / pharmacology
Receptors, Neurokinin-2 / antagonists & inhibitors
Receptors, Neurokinin-3 / antagonists & inhibitors
Receptors, Tachykinin / antagonists & inhibitors*
Sensitivity and Specificity
Structure-Activity Relationship

Substances

Benzimidazoles
Neurokinin-1 Receptor Antagonists
Oximes
Receptors, Neurokinin-2
Receptors, Neurokinin-3
Receptors, Tachykinin