Synthesis and Cannabinoid Activity of a Variety of 2,3-Substituted 1-Benzo[b]thiophen Derivatives and 2,3-Substituted Benzofuran: Novel Agonists for the CB1 Receptor

Gerard P. Moloney; James A. Angus; Alan D. Robertson; Martin J. Stoermer; Michael Robinson; Lucy Lay; Christine E. Wright; Ken McRae; Arthur Christopoulos

doi:10.1071/CH07412

RESEARCH ARTICLE

Synthesis and Cannabinoid Activity of a Variety of 2,3-Substituted 1-Benzo[b]thiophen Derivatives and 2,3-Substituted Benzofuran: Novel Agonists for the CB₁ Receptor

Gerard P. Moloney ^A ^E , James A. Angus ^B , Alan D. Robertson ^C , Martin J. Stoermer ^A , Michael Robinson ^A , Lucy Lay ^B , Christine E. Wright ^B , Ken McRae ^A and Arthur Christopoulos ^D

+ Author Affiliations

- Author Affiliations

^A Department of Medicinal Chemistry, Victorian College of Pharmacy (Monash University), 381 Royal Parade, Parkville VIC 3052, Australia.

^B Cardiovascular Therapeutics Unit, Department of Pharmacology, University of Melbourne, VIC 3010, Australia.

^C AMRAD Corporation Limited (now known as Zenyth Therapeutics Limited), 576 Swan Street, Richmond VIC 3121, Australia.

^D Drug Discovery Laboratory, Department of Pharmacology, Monash University, VIC 3800, Australia.

^E Corresponding author. Email: gerard.moloney@vcp.monash.edu.au

Australian Journal of Chemistry 61(7) 484-499 https://doi.org/10.1071/CH07412
Submitted: 29 November 2007 Accepted: 31 May 2008 Published: 16 July 2008

Abstract

An exploratory chemical effort has been undertaken to develop a novel series of compounds as selective CB₁ agonists. It is hoped that compounds of this type will have clinical utility in pain control and cerebral ischaemia following stroke or traumatic head injury. We report here medicinal chemistry studies directed towards the investigation of several classes of 1-benzo[b]thiophen and benzofuran derivatives as novel CB₁ agonists. We have discovered a novel series of compounds, which contain a 1-benzo[b]thiophen or a benzofuran group as the central aromatic group. Our investigation of this series of compounds has enhanced our understanding of the importance of binding sites within the CB₁ receptor for favourable CB₁ potency. Our understanding of these factors allowed us to modify the structure of a 1-benzothiophen derivative and improve its potency at the CB₁ receptor.

References

Synthesis and Cannabinoid Activity of a Variety of 2,3-Substituted 1-Benzo[b]thiophen Derivatives and 2,3-Substituted Benzofuran: Novel Agonists for the CB1 Receptor

Abstract

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Synthesis and Cannabinoid Activity of a Variety of 2,3-Substituted 1-Benzo[b]thiophen Derivatives and 2,3-Substituted Benzofuran: Novel Agonists for the CB₁ Receptor