Bioisosteric replacement of dihydropyrazole of 4S-(-)-3-(4-chlorophenyl)-N-methyl-N′-[(4-chlorophenyl)-sulfonyl]- 4-phenyl-4,5-dihydro-1H-pyrazole-1-caboxamidine (SLV-319) a potent CB1 receptor antagonist by imidazole and oxazole

Abstract

Design, synthesis and conformational analysis of few imidazole and oxazole as bioisosters of 4S-(-)-3-(4-chlorophenyl)-N-methyl-N′-[(4-chlorophenyl)-sulfonyl]- 4-phenyl-4,5-dihydro-1H-pyrazole-1-caboxamidine (SLV-319) 2 is reported. Computer assisted conformational analysis gave a direct clue for the loss of CB1 antagonistic activity of the ligands without a fine docking simulation for the homology model. © 2007 Elsevier Ltd. All rights reserved.