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.
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
Steven J
SJ
Coats
Mark J
MJ
Schulz
John R
JR
Carson
Ellen E
EE
Codd
Dennis J
DJ
Hlasta
Philip M
PM
Pitis
Dennis J
DJ
Stone
Sui-Po
SP
Zhang
Ray W
RW
Colburn
Scott L
SL
Dax
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