title: 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.
authors.affiliation: Department of Medicinal Chemistry, Zydus Research Centre, Cadila Healthcare Ltd, Sarkhej-Bavla N.H. 8A, Moraiya, Ahmedabad 382210, India. brijeshsrivastava@zyduscadila.com
authors.forename: Brijesh Kumar
authors.initials: BK
authors.lastname: Srivastava
authors.forename: Rina
authors.initials: R
authors.lastname: Soni
authors.forename: Amit
authors.initials: A
authors.lastname: Joharapurkar
authors.forename: Kalapatapu V V M
authors.initials: KV
authors.lastname: Sairam
authors.forename: Jayendra Z
authors.initials: JZ
authors.lastname: Patel
authors.forename: Amitgiri
authors.initials: A
authors.lastname: Goswami
authors.forename: Sandeep A
authors.initials: SA
authors.lastname: Shedage
authors.forename: Sidhartha S
authors.initials: SS
authors.lastname: Kar
authors.forename: Rahul P
authors.initials: RP
authors.lastname: Salunke
authors.forename: Shivaji B
authors.initials: SB
authors.lastname: Gugale
authors.forename: Amol
authors.initials: A
authors.lastname: Dhawas
authors.forename: Pravin
authors.initials: P
authors.lastname: Kadam
authors.forename: Bhupendra
authors.initials: B
authors.lastname: Mishra
authors.forename: Nisha
authors.initials: N
authors.lastname: Sadhwani
authors.forename: Vishal B
authors.initials: VB
authors.lastname: Unadkat
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Mitra
authors.forename: Mukul R
authors.initials: MR
authors.lastname: Jain
authors.forename: Pankaj R
authors.initials: PR
authors.lastname: Patel
mesh_terms: 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*
chemical_list: 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