Synthesis and structure-activity relationships of a series of pyrrole cannabinoid receptor agonists |
| |
Authors: | Tarzia Giorgio Duranti Andrea Tontini Andrea Spadoni Gilberto Mor Marco Rivara Silvia Vincenzo Plazzi Pier Kathuria Satish Piomelli Daniele |
| |
Affiliation: | Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Urbino Carlo Bo, Piazza del Rinascimento 6, I-61029 Urbino, Italy. gat@uniurb.it |
| |
Abstract: | We designed and synthesized a series of pyrrole derivatives with the aim of investigating the structure-activity relationship (SAR) for the binding of non-classical agonists to CB(1) and CB(2) cannabinoid receptors. Superposition of two pyrrole-containing cannabinoid agonists, JWH-007 and JWH-161, allowed us to identify positions 1, 3 and 4 of the pyrrole nucleus as amenable to additional investigation. We prepared the 1-alkyl-2,5-dimethyl-3,4-substituted pyrroles 10a-e, 11a-d, 17, 21, 25 and the tetrahydroindole 15, and evaluated their ability to bind to and activate cannabinoid receptors. Noteworthy in this set of compounds are the 4-bromopyrrole 11a, which has an affinity for CB(1) and CB(2) receptors comparable to that of well-characterized heterocyclic cannabimimetics such as Win-55,212-2; the amide 25, which, although possessing a moderate affinity for cannabinoid receptors, demonstrates that the 3-naphthoyl group, commonly present in indole and pyrrole cannabimimetics, can be substituted by alternative moieties; and compounds 10d, 11d, showing CB(1) partial agonist properties. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|