Structure-activity relationships of oxime neurokinin antagonists: oxime modifications.
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.
Reichard
Gregory A
GA
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. gregory.reichard@spcorp.com
Spitler
James
J
Aslanian
Robert
R
Mutahi
Mwangi wa
Mw
Shih
Neng Yang
NY
Lin
Ling
L
Ting
Pauline C
PC
Anthes
John C
JC
Piwinski
John J
JJ
D000818:Animals; D019540:Area Under Curve; D006168:Guinea Pigs; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010091:Oximes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D064729:Neurokinin-1 Receptor Antagonists; D010091:Oximes; D018041:Receptors, Neurokinin-2