title: Indole-2-carboxamides as allosteric modulators of the cannabinoid CB₁ receptor.
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.
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Piscitelli
authors.forename: Alessia
authors.initials: A
authors.lastname: Ligresti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Regina
authors.forename: Antonio
authors.initials: A
authors.lastname: Coluccia
authors.forename: Ludovica
authors.initials: L
authors.lastname: Morera
authors.forename: Marco
authors.initials: M
authors.lastname: Allarà
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
mesh_terms: D000494:Allosteric Regulation; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D007211:Indoles; D010879:Piperazines; D010880:Piperidines; D011759:Pyrrolidines; D043884:Receptor, Cannabinoid, CB1; D011994:Recombinant Proteins