title: Novel pyrazole-3-carboxamide derivatives as cannabinoid-1 (CB1) antagonists: journey from non-polar to polar amides.
abstract: The synthesis and biological evaluation of novel pyrazole-3-carboxamide derivatives as CB1 antagonists are described. As a part of eastern amide SAR, various chemically diverse motifs were introduced. In general, a range of modifications were well tolerated. Several molecules with high polar surface area were also identified as potent CB1 receptor antagonists. The in vivo proof of principle for weight loss is exemplified with a lead compound from this series.
authors.affiliation: Discovery Research, Dr Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad 500049, India. pradipks@drreddys.com
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Sasmal
authors.forename: D Srinivasa
authors.initials: DS
authors.lastname: Reddy
authors.forename: Rashmi
authors.initials: R
authors.lastname: Talwar
authors.forename: B
authors.initials: B
authors.lastname: Venkatesham
authors.forename: D
authors.initials: D
authors.lastname: Balasubrahmanyam
authors.forename: M
authors.initials: M
authors.lastname: Kannan
authors.forename: P
authors.initials: P
authors.lastname: Srinivas
authors.forename: Shiva K
authors.initials: SK
authors.lastname: Kyasa
authors.forename: B Neelima
authors.initials: BN
authors.lastname: Devi
authors.forename: Vikram P
authors.initials: VP
authors.lastname: Jadhav
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Khan
authors.forename: Priya
authors.initials: P
authors.lastname: Mohan
authors.forename: Hira
authors.initials: H
authors.lastname: Chaudhury
authors.forename: Debnath
authors.initials: D
authors.lastname: Bhuniya
authors.forename: Javed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Ranjan
authors.initials: R
authors.lastname: Chakrabarti
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D051379:Mice; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000577:Amides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013777:Tetrazoles