Structure–activity relationships of 2-arylamido-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxamide derivatives as cannabinoid receptor agonists and their analgesic action

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 24; pp. 7314 - 7321
• Main Authors: Thur, Yithachu, Bhalerao, Amit, Munshi, Zaki, Pansare, Nisha, Mann, Klaus, Hanauer, Guido, Kley, Hans-Peter, Nappe, Sandra, Weiss-Haljiti, Cornelia, Ostermann, Claude, Zitt, Christof, Schaefer, Michaela, Mondal, Dibyendu, Ali Siddiki, Afsar, Armugam, Velavan, Gudaghe, Vinod, Gupta, Mahendra, Rayudu, Pramila, Dautzenberg, Frank M., Das Sarma, Koushik
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-12-2012; Elsevier
• Subjects: Animals; Biological and medical sciences; CB2 agonists; GPCR; HTS; Humans; Inflammatory pain models; Medical sciences; Molecular Structure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Pyrans - chemical synthesis; Pyrans - chemistry; Pyrans - pharmacology; Rats; Receptors, Cannabinoid - metabolism; SAR; Structure-Activity Relationship; Thiophenes - chemical synthesis; Thiophenes - chemistry; Thiophenes - pharmacology; GPCR; Inflammatory pain models; CB2 agonists; SAR; HTS; Agonist; CB2 cannabinoid receptor; Analgesic; Structure activity relation; G protein coupled receptor; Cannabinoid receptor; Carboxamide; Models
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.10.087

SAR studies were performed on a series of 2-arylamido-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxamide derivatives as cannabinoid receptor agonists. Starting from HTS hit both potency and selectivity could be improved. Modifications to the thiophene fusion and C-3 amides were studied. A representative compound 3t produced analgesia when dosed orally in inflammatory pain models of writhing and carrageenan-induced allodynia.
SAR studies were performed on a series of 2-arylamido-5,7-dihydro-4H-thieno[2,3-c]pyran-3-carboxamide derivatives as cannabinoid receptor agonists. Starting from a HTS hit both potency and selectivity could be improved. Modifications to the thiophene fusion and C-3 amides were studied. A representative compound 3t produced analgesia when dosed orally in inflammatory pain models of writhing and carrageenan-induced allodynia.