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Tricyclic pyrazoles. Part 2: Synthesis and biological evaluation of novel 4,5-dihydro-1 H -benzo[ g ]indazole-based ligands for cannabinoid receptors

Bioorganic & Medicinal Chemistry, ISSN: 0968-0896, Vol: 13, Issue: 9, Page: 3309-3320
2005
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Article Description

A series of 4,5-dihydro-1 H -benzo[ g ]indazole-3-carboxamides ( 2a – k ) as analogues of the previously reported CB 2 ligands 6-chloro- and 6-methyl-1-(2′,4′-dichlorophenyl)- N -piperidin-1-yl-1,4-dihydroindeno[1,2- c ]pyrazole-3-carboxamides ( 1a, b ) was synthesized and their affinity and selectivity towards CB 1 and CB 2 receptors were evaluated. Several of the new compounds ( 2a, b, c, d and i ) exhibited CB 1 affinity in the nanomolar range with moderate or negligible affinity towards CB 2 receptors. Compounds 2a and c increased intestinal propulsion in mouse. Their pro-kinetic effects were reversed by the reference CB agonist CP-55,940. Consequently, in vivo CB 1 antagonistic activity was highlighted for these compounds.

Bibliographic Details

Murineddu, Gabriele; Ruiu, Stefania; Mussinu, Jean-Mario; Loriga, Giovanni; Grella, Giuseppe E; Carai, Mauro A M; Lazzari, Paolo; Pani, Luca; Pinna, Gérard A

Elsevier BV

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics; Chemistry

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