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.
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.
Srivastava
Brijesh Kumar
BK
Department of Medicinal Chemistry, Zydus Research Centre, Cadila Healthcare Ltd, Sarkhej-Bavla N.H. 8A, Moraiya, Ahmedabad 382210, India. brijeshsrivastava@zyduscadila.com
Soni
Rina
R
Joharapurkar
Amit
A
Sairam
Kalapatapu V V M
KV
Patel
Jayendra Z
JZ
Goswami
Amitgiri
A
Shedage
Sandeep A
SA
Kar
Sidhartha S
SS
Salunke
Rahul P
RP
Gugale
Shivaji B
SB
Dhawas
Amol
A
Kadam
Pravin
P
Mishra
Bhupendra
B
Sadhwani
Nisha
N
Unadkat
Vishal B
VB
Mitra
Prasenjit
P
Jain
Mukul R
MR
Patel
Pankaj R
PR
D000818:Animals; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
C482795:3-(4-chlorophenyl)-N-methyl-N'-((4-chlorophenyl)sulfonyl)-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamidine; D007093:Imidazoles; D010080:Oxazoles; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013449:Sulfonamides