1,4-Diazepane compounds as potent and selective CB2 agonists: optimization of metabolic stability

Doris Riether; Lifen Wu; Pier F Cirillo; Angela Berry; Edward R Walker; Monika Ermann; Beatriz Noya-Marino; James E Jenkins; Dan Albaugh; Claudia Albrecht; Michael Fisher; Mark J Gemkow; Heather Grbic; Sabine Löbbe; Clemens Möller; Kathy O'Shea; Achim Sauer; Daw-Tsun Shih; David S Thomson

doi:10.1016/j.bmcl.2011.02.017

1,4-Diazepane compounds as potent and selective CB2 agonists: optimization of metabolic stability

Bioorg Med Chem Lett. 2011 Apr 1;21(7):2011-6. doi: 10.1016/j.bmcl.2011.02.017. Epub 2011 Feb 25.

Affiliation

¹ Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc, 900 Ridgebury Road, Ridgefield, CT 06877, USA. [email protected]

PMID: 21354795
DOI: 10.1016/j.bmcl.2011.02.017

Abstract

A high-throughput screening campaign has identified 1,4-diazepane compounds which are potent Cannabinoid receptor 2 agonists with excellent selectivity against the Cannabinoid receptor 1. This class of compounds suffered from low metabolic stability. Following various strategies, compounds with a good stability in liver microsomes and rat PK profile have been identified.

MeSH terms

Animals
Azepines / chemistry
Azepines / pharmacology*
Microsomes, Liver / metabolism
Rats
Rats, Wistar
Receptor, Cannabinoid, CB2 / agonists*

Substances

1,4-diazepane
Azepines
Receptor, Cannabinoid, CB2