High affinity, selective neurokinin 2 and neurokinin 3 receptor antagonists from a common structural template.
High affinity, selective hNK2 or hNK3 ligands can be prepared from the common template 1 in a few simple chemical operations. The hNK3 ligands 3 antagonise the calcium mobilisation caused by activation of hNK3 receptors expressed in CHO cells as measured using fura-2 microspectrofluorimetry.
Harrison
T
T
Department of Medicinal Chemistry, Merck Sharp Laboratory, Essex, U.K. timothy_harrison@merck.com
Korsgaard
M P
MP
Swain
C J
CJ
Cascieri
M A
MA
Sadowski
S
S
Seabrook
G R
GR
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D007769:Lactams / Q000138:chemical synthesis* / Q000494:pharmacology; D008968:Molecular Conformation; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
D005456:Fluorescent Dyes; D007769:Lactams; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D002118:Calcium; D016257:Fura-2