- Synthesis, SAR and intramolecular hydrogen bonding pattern of 1,3,5-trisubstituted 4,5-dihydropyrazoles as potent cannabinoid CB1 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 CB1 r
- Lange, Jos H.M.,van der Neut, Martina A.W.,den Hartog, Arnold P.,Wals, Henri C.,Hoogendoorn, Jan,van Stuivenberg, Herman H.,van Vliet, Bernard J.,Kruse, Chris G.
-
experimental part
p. 1752 - 1757
(2010/07/08)
-
- Diaryl dihydropyrazole-3-carboxamides with significant in vivo antiobesity activity related to CB1 receptor antagonism: Synthesis, biological evaluation, and molecular modeling in the homology model
-
A number of analogues of diaryl dihydropyrazole-3-carboxamides have been synthesized. Their activities were evaluated for appetite suppression and body weight reduction in animal models. Depending on the chemical modification of the selected dihydropyrazole scaffold, the lead compounds - the bisulfate salt of (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid morpholin-4-ylamide 26 and the bisulfate salt of (-)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3- carboxylic acid morpholin-4-ylamide 30-showed significant body weight reduction in vivo, which is attributed to their CB1 antagonistic activity and exhibited a favorable pharmacokinetic profile. The molecular modeling studies also showed interactions of two isomers of (±)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 9 with CB1 receptor in the homology model similar to those of N-piperidino-5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (rimonabant) 1 and 4S-(-)-3-(4-chlorophenyl)-N-methyl-N′-[(4-chlorophenyl) -sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamidine (SLV-319) 2.
- Srivastava, Brijesh Kumar,Joharapurkar, Amit,Raval, Saurin,Patel, Jayendra Z.,Soni, Rina,Raval, Preeti,Gite, Archana,Goswami, Amitgiri,Sadhwani, Nisha,Gandhi, Neha,Patel, Harilal,Mishra, Bhupendra,Solanki, Manish,Pandey, Bipin,Jain, Mukul R.,Patel, Pankaj R.
-
p. 5951 - 5966
(2008/04/12)
-
- 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazole derivatives having CB1-antagonistic activity
-
The present invention relates to 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazole derivatives as CB1 antagonists, to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said pyrazole derivatives. Th
- -
-
Page/Page column 6-7
(2010/02/13)
-