title: Tetrahydro-β-carboline derivatives targeting fatty acid amide hydrolase (FAAH) and transient receptor potential (TRP) channels.
abstract: A series of twenty-five derivatives of tetrahydro-β-carbolines 1-3 was synthesized and assayed on FAAH and TRPV1 and TRPA1 channels. Four carbamates, that is, 5a,c,e, and 9b inhibited FAAH with significant potency and interacted also effectively with TRPV1 and TRPA1 nociceptive receptors, while ureas 7b,d,f, and 8a,b were endowed with specific submicromolar TRPV1 modulating activities.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, piazzale Aldo Moro 5, 00185 Roma, Italy. giorgio.ortar@uniroma1.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ortar
authors.forename: Luciano
authors.initials: L
authors.lastname: De Petrocellis
authors.forename: Aniello Schiano
authors.initials: AS
authors.lastname: Moriello
authors.forename: Marco
authors.initials: M
authors.lastname: Allarà
authors.forename: Enrico
authors.initials: E
authors.lastname: Morera
authors.forename: Marianna
authors.initials: M
authors.lastname: Nalli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002219:Carbamates / Q000737:chemistry; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014508:Urea / Q000737:chemistry; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000700:Analgesics; D015220:Calcium Channels; D002219:Carbamates; D002243:Carbolines; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; D050051:Transient Receptor Potential Channels; D014508:Urea; D000099252:Fatty Acid Amide Hydrolases; C473350:TRPA1 protein, human; C494482:TRPV1 protein, human