title: Design, synthesis and biological evaluation of novel pyrazolo-pyrimidinones as DPP-IV inhibitors in diabetes.
abstract: We report the design, synthesis, biological activity and docking studies of series of novel pyrazolo[3,4-d]pyrimidinones as DPP-IV inhibitors in diabetes. Molecules were synthesized and evaluated for their DPP-IV inhibition activity. Compounds 5e, 5k, 5o and 6a were found to be potent inhibitors of DPP-IV enzyme. Amongst all the synthesized compounds, 6-methyl-5-(4-methylpyridin-2-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (5k) was found to be the most active based on in vitro DPP-IV studies and also exhibited promising in vivo blood glucose lowering activity in male Wistar rats.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Ahmedabad, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India; Department of Medicinal Chemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India.
authors.forename: Sneha R
authors.initials: SR
authors.lastname: Sagar
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research-Ahmedabad, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Agarwal
authors.affiliation: Department of Medicinal Chemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India.
authors.forename: Dhaivat H
authors.initials: DH
authors.lastname: Pandya
authors.affiliation: Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India.
authors.forename: Ranjeet Prasad
authors.initials: RP
authors.lastname: Dash
authors.affiliation: Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Nivsarkar
authors.affiliation: Department of Medicinal Chemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad 380054, Gujarat, India. Electronic address: kamalav@perdcentre.com.
authors.forename: Kamala K
authors.initials: KK
authors.lastname: Vasu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006943:Hyperglycemia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011720:Pyrazoles; D011744:Pyrimidinones; C031280:pyrazole; C000602659:DPP4 protein, rat; D018819:Dipeptidyl Peptidase 4
keywords: DPP-IV enzyme; Molecular docking; Pyrazolo-pyrimidinones