N,N-dialkyl-4-[(8-azabicyclo[3.2.1]-oct-3-ylidene)phenylmethyl]benzamides, potent, selective delta opioid agonists.
A series of N,N-dialkyl-4-(9-aryltropanylidenemethyl)benzamides was prepared. The lead compounds, 15a and 15c, exhibited extremely high affinity for the delta opioid receptor with excellent selectivity versus the micro opioid receptor. They were full agonists at the delta opioid receptor, as assessed by stimulation of GTPgammaS binding, and displayed antinociceptive activity.
Carson
John R
JR
Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, LLC, Welsh and McKean Roads, PO 776, Spring House, PA 19477-0776, USA. jcarson@prdus.jnj.com
Coats
Steven J
SJ
Codd
Ellen E
EE
Dax
Scott L
SL
Lee
Jung
J
Martinez
Rebecca P
RP
Neilson
Lou Anne
LA
Pitis
Philip M
PM
Zhang
Sui-Po
SP
D000701:Analgesics, Opioid / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000819:agonists*; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D001549:Benzamides; D017465:Receptors, Opioid, delta; D016244:Guanosine 5'-O-(3-Thiotriphosphate)