Indole-2-carboxamides as allosteric modulators of the cannabinoid CB₁ receptor

  • J Med Chem. 2012 Jun 14;55(11):5627-31. doi: 10.1021/jm201485c.
Francesco Piscitelli  1 ,  Alessia Ligresti ,  Giuseppe La Regina ,  Antonio Coluccia ,  Ludovica Morera ,  Marco Allarà ,  Ettore Novellino ,  Vincenzo Di Marzo ,  Romano Silvestri
Affiliations
  • 1. Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
PMID: 22571451 DOI: 10.1021/jm201485c
Abstract

We synthesized new N-phenylethyl-1H-indole-2-carboxamides as the first SAR study of allosteric modulators of the CB(1) receptor. The presence of the carboxamide functionality was required in order to obtain a stimulatory effect. The maximum stimulatory activity on CB(1) was exerted by carboxamides 13 (EC(50) = 50 nM) and 21 (EC(50) = 90 nM) bearing a dimethylamino or piperidinyl group, respectively, at position 4 of the phenethyl moiety and a chlorine atom at position 5 of the indole.