Synthesis and biological evaluation of new N-alkyl 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides as cannabinoid receptor ligands.

Abstract:

:A series of N-alkyl 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides were synthesized as new ligands of the human recombinant receptor hCB1. n-Alkyl carboxamides brought out different SARs from the branched subgroup. Unsubstituted pyrrole derivatives bearing a tert-alkyl chain at the 3-carboxamide nitrogen showed greater hCB1 receptor affinity than the corresponding unbranched compounds. In particular, the tert-butyl group as a chain terminal moiety strongly improved hCB1 receptor affinity (compound 24: Ki=45.6 nM; 29: Ki=37.5 nM). Acute administration of either compound 12 or 29 resulted in a specific, dose-dependent reduction in food intake in rats. Such results provide an useful basis for the design of new CB1 ligands.

journal_name

Eur J Med Chem

authors

Silvestri R,Ligresti A,La Regina G,Piscitelli F,Gatti V,Lavecchia A,Brizzi A,Pasquini S,Allarà M,Fantini N,Carai MA,Bigogno C,Rozio MG,Sinisi R,Novellino E,Colombo G,Di Marzo V,Dondio G,Corelli F

doi

10.1016/j.ejmech.2010.09.053

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

5878-86

issue

12

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(10)00702-6

journal_volume

45

pub_type

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