Parallel methods for the preparation and SAR exploration of N-ethyl-4-[(8-alkyl-8-aza-bicyclo[3.2.1]oct-3-ylidene)-aryl-methyl]-benzamides, powerful mu and delta opioid agonists.
Two parallel synthetic methods were developed to explore the structure-activity relationships (SAR) of a series of potent opioid agonists. This series of tropanylidene benzamides proved extremely tolerant of structural variation while maintaining excellent opioid activity. Evaluation of several representative compounds from this series in the mouse hot plate test revealed potent antinociceptive effects upon oral administration.
Coats
Steven J
SJ
Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, PO Box 776, Spring House, PA 19477-0776, USA. scoats@prdus.jnj.com
Schulz
Mark J
MJ
Carson
John R
JR
Codd
Ellen E
EE
Hlasta
Dennis J
DJ
Pitis
Philip M
PM
Stone
Dennis J
DJ
Zhang
Sui-Po
SP
Colburn
Ray W
RW
Dax
Scott L
SL
D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D010147:Pain Measurement / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013329:Structure-Activity Relationship
D000700:Analgesics; D001549:Benzamides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu