The design and synthesis of novel NK1/NK2 dual antagonists.
Functional probing of the backbone of the Sanofi NK2 antagonist SR 48968 has resulted in the discovery of two new classes of NK1/NK2 dual antagonists: the diamine class and the oxime class. The addition of the amino or the oxime functional group results in the reversal of the stereochemical preference of the NK2 receptor.
Reichard
G A
GA
Schering-Plough Research Institute, Kenilwrorth, NJ 07033-1300, USA. gregory.reichard@spcorp.com
Ball
Z T
ZT
Aslanian
R
R
Anthes
J C
JC
Shih
N Y
NY
Piwinski
J J
JJ
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D003959:Diamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D007700:Kinetics; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001549:Benzamides; D003959:Diamines; D064729:Neurokinin-1 Receptor Antagonists; D010091:Oximes; D010880:Piperidines; D018041:Receptors, Neurokinin-2; C073839:SR 48968