Rapid access towards follow-up NOP receptor agonists using a knowledge based approach.
A knowledge based approach has been adopted to identify novel NOP receptor agonists with simplified hydrophobes. Substitution of the benzimidazol-2-one piperidine motif with a range of hydrophobic groups and pharmacophore guided bio-isosteric replacement of the benzimidazol-2-one moiety was explored. Compound 51 was found to be a high affinity, potent NOP receptor agonist with reduced affinity for the hERG channel.
Palin
Ronald
R
Department of Chemistry, Schering-Plough Research Institute, Newhouse, Lanarkshire ML15SH, UK. ronald.palin@spcorp.com
Clark
John K
JK
Evans
Louise
L
Feilden
Helen
H
Fletcher
Dan
D
Hamilton
Niall M
NM
Houghton
Andrea K
AK
Jones
Philip S
PS
McArthur
Duncan
D
Montgomery
Brian
B
Ratcliffe
Paul D
PD
Smith
Alasdair R C
AR
Sutherland
Aaron
A
Weston
Mark A
MA
Wishart
Grant
G
D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry*; D006224:Cricetinae; D009292:Narcotic Antagonists / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D011957:Receptors, Opioid / Q000378:metabolism; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
D001562:Benzimidazoles; D009292:Narcotic Antagonists; D010880:Piperidines; D011957:Receptors, Opioid; C053110:benzimidazol-2-one; C032727:piperidine; D000094942:Nociceptin Receptor