Synthesis, SAR and intramolecular hydrogen bonding pattern of 1,3,5-trisubstituted 4,5-dihydropyrazoles as potent cannabinoid CB(1) receptor antagonists.
The synthesis, structure-activity relationship (SAR) studies and intramolecular hydrogen bonding pattern of 1,3,5-trisubstituted 4,5-dihydropyrazoles are described. The target compounds 6-18 represent a novel class of potent and selective CB(1) receptor antagonists. Based on X-ray diffraction data, the orally active 17 is shown to elicit a different intramolecular H-bonding mode as compared to ibipinabant (3) and SLV330 (4).
Lange
Jos H M
JH
Solvay Pharmaceuticals, Research Laboratories, Chemical Design & Synthesis Unit, C. J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands. jos.lange@solvay.com
van der Neut
Martina A W
MA
den Hartog
Arnold P
AP
Wals
Henri C
HC
Hoogendoorn
Jan
J
van Stuivenberg
Herman H
HH
van Vliet
Bernard J
BJ
Kruse
Chris G
CG
D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D019440:Anti-Obesity Agents; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013449:Sulfonamides