Biphenyl derivatives as novel dual NK(1)/NK(2)-receptor antagonists.
In a continuation of our efforts to simplify the structure of our neurokinin antagonists, a series of substituted biphenyl derivatives has been prepared. Several compounds exhibit potent affinities for both the NK(1) receptor (<10nM) and for the NK(2) receptor (<50 nM). Details on the design, synthesis, biological activities, SAR and conformational analysis of this new class of dual NK(1)/NK(2) receptor antagonists are presented.
Pharma Research, Novartis Pharma AG, CH-4002, Basel, Switzerland. robert.mah@speedelgroup.com
Robert
R
Mah
Marc
M
Gerspacher
Andreas
A
von Sprecher
Stefan
S
Stutz
Vincenzo
V
Tschinke
Gary P
GP
Anderson
Claude
C
Bertrand
Natarajan
N
Subramanian
Howard A
HA
Ball
D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D006168:Guinea Pigs; D006801:Humans; D008968:Molecular Conformation; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D018041:Receptors, Neurokinin-2