Tetrahydro-β-carboline derivatives targeting fatty acid amide hydrolase (FAAH) and transient receptor potential (TRP) channels

• Published in: Bioorganic & medicinal chemistry letters 2013-01, Vol.23 (1), p.138-142
• Main Authors: Ortar, Giorgio, Petrocellis, Luciano De, Moriello, Aniello Schiano, Allarà, Marco, Morera, Enrico, Nalli, Marianna, Marzo, Vincenzo Di
• Format: Article
• Language: English
• Subjects: Amidohydrolases - antagonists & inhibitors; Amidohydrolases - metabolism; Analgesics - chemical synthesis; Analgesics - chemistry; Analgesics - metabolism; Calcium Channels - metabolism; carbamates; Carbamates - chemistry; Carbolines - chemical synthesis; Carbolines - chemistry; Carbolines - metabolism; chemistry; FAAH; fatty acids; Humans; Nerve Tissue Proteins - antagonists & inhibitors; Nerve Tissue Proteins - metabolism; Protein Binding; receptors; Structure-Activity Relationship; Tetrahydro-β-carbolines; Transient receptor potential channels; Transient Receptor Potential Channels - antagonists & inhibitors; Transient Receptor Potential Channels - metabolism; TRPA1; TRPA1 Cation Channel; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - metabolism; TRPV1; Urea - chemistry
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.10.137

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.