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

Steven J Coats; Mark J Schulz; John R Carson; Ellen E Codd; Dennis J Hlasta; Philip M Pitis; Dennis J Stone Jr; Sui-Po Zhang; Ray W Colburn; Scott L Dax

doi:10.1016/j.bmcl.2004.09.004

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

Bioorg Med Chem Lett. 2004 Nov 15;14(22):5493-8. doi: 10.1016/j.bmcl.2004.09.004.

Authors

Steven J Coats¹, Mark J Schulz, John R Carson, Ellen E Codd, Dennis J Hlasta, Philip M Pitis, Dennis J Stone Jr, Sui-Po Zhang, Ray W Colburn, Scott L Dax

Affiliation

¹ 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

PMID: 15482911
DOI: 10.1016/j.bmcl.2004.09.004

Abstract

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.

MeSH terms

Analgesics* / chemical synthesis
Analgesics* / chemistry
Animals
Benzamides* / chemical synthesis
Benzamides* / chemistry
Mice
Molecular Structure
Pain Measurement / drug effects
Receptors, Opioid, delta / agonists*
Receptors, Opioid, mu / agonists*
Structure-Activity Relationship

Substances

Analgesics
Benzamides
Receptors, Opioid, delta
Receptors, Opioid, mu