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Novel pyrrolocycloalkylpyrazole analogues as CB 1 ligands
Author(s) -
Asproni Battistina,
Manca Ilaria,
Pinna Giansalvo,
Cichero Elena,
Fossa Paola,
Murineddu Gabriele,
Lazzari Paolo,
Loriga Giovanni,
Pinna Gérard A.
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13069
Subject(s) - cannabinoid receptor , chemistry , indolizine , azepine , stereochemistry , cannabinoid , cannabinoid receptor type 2 , docking (animal) , carboxamide , receptor , biochemistry , antagonist , medicine , nursing
Novel 1,4‐dihydropyrazolo[3,4‐ a ]pyrrolizine‐, 4,5‐dihydro‐1 H ‐pyrazolo[4,3‐ g ]indolizine‐ and 1,4,5,6‐tetrahydropyrazolo[3,4‐ c ]pyrrolo[1,2‐ a ]azepine‐3‐carboxamide‐based compounds were designed and synthesized for cannabinoid CB 1 and CB 2 receptor interactions. Any of the new synthesized compounds showed high affinity for CB 2 receptor with K i values superior to 314 n m , whereas some of them showed moderate affinity for CB 1 receptor with K i values inferior to 400 n m . 7‐Chloro‐1‐(2,4‐dichlorophenyl) ‐N‐ (homopiperidin‐1‐yl)‐4,5‐dihydro‐1 H ‐pyrazolo[4,3 ‐g ]indolizine‐3‐carboxamide ( 2j ) exhibited good affinity for CB 1 receptor ( K i CB 1 = 81 n m ) and the highest CB 2 / CB 1 selectively ratio (>12). Docking studies carried out on such compounds were performed using the hCB 1 X‐ray in complex with the close pyrazole analogue AM 6538 and disclosed specific pattern of interactions related to the tricyclic pyrrolopyrazole scaffolds as CB 1 ligands.