Piperazinyl oxime ethers as NK-1 receptor antagonists.
The synthesis and structure-activity relations for a new class of centrally active NK-1 receptor antagonists are described. The new compounds are based on piperazine 2 and contain an oxime ether functionality. Several new compounds have high affinity for the NK-1 receptor and show good antagonistic activity in the gerbil foot-tapping assay.
van den Hoogenband
Adri
A
Solvay Pharmaceuticals, Research Laboratories, C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
van Maarseveen
Jan H
JH
McCreary
Andrew C
AC
Mulder
Arie T
AT
van Scharrenburg
Guus J M
GJ
van Stuivenberg
Herman H
HH
Zethof
Theo J J
TJ
Zijta
Barbara
B
Iwema Bakker
Wouter I
WI
D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D016466:CHO Cells; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D004987:Ethers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D005849:Gerbillinae; D006801:Humans; D008968:Molecular Conformation; D009043:Motor Activity / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D010091:Oximes / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D004987:Ethers; D064729:Neurokinin-1 Receptor Antagonists; D010091:Oximes; D010446:Peptide Fragments; D010879:Piperazines; C068032:GR 73632; D013373:Substance P