Structure-activity relationships of oxime neurokinin antagonists: oxime modifications

Gregory A Reichard; James Spitler; Robert Aslanian; Mwangi wa Mutahi; Neng Yang Shih; Ling Lin; Pauline C Ting; John C Anthes; John J Piwinski

doi:10.1016/s0960-894x(02)00027-6

Structure-activity relationships of oxime neurokinin antagonists: oxime modifications

Bioorg Med Chem Lett. 2002 Mar 11;12(5):833-6. doi: 10.1016/s0960-894x(02)00027-6.

Authors

Gregory A Reichard¹, James Spitler, Robert Aslanian, Mwangi wa Mutahi, Neng Yang Shih, Ling Lin, Pauline C Ting, John C Anthes, John J Piwinski

Affiliation

¹ Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. [email protected]

PMID: 11859013
DOI: 10.1016/s0960-894x(02)00027-6

Abstract

A thorough SAR study of the oxime region of the dual NK(1)/NK(2) antagonist 1 revealed several modifications that result in potent dual antagonists. Follow up SAR studies on a second-generation scaffold demonstrate that certain polar groups on the oxime can improve the dual binding affinity to the subnanomolar range.

MeSH terms

Animals
Area Under Curve
Guinea Pigs
Molecular Structure
Neurokinin-1 Receptor Antagonists*
Oximes / chemical synthesis*
Oximes / metabolism
Oximes / pharmacology*
Rats
Receptors, Neurokinin-2 / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Neurokinin-1 Receptor Antagonists
Oximes
Receptors, Neurokinin-2