title: Design, synthesis and biological evaluation of novel aminomethyl-piperidones based DPP-IV inhibitors.
abstract: A series of novel aminomethyl-piperidones were designed and evaluated as potential DPP-IV inhibitors. Optimized analogue 12v ((4S,5S)-5-(aminomethyl)-1-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-4-(2,5-difluorophenyl)piperidin-2-one) showed excellent in vitro potency and selectivity for DPP-IV over other serine proteases. The lead compound 12v showed potent and long acting antihyperglycemic effects (in vivo), along with improved pharmacokinetic profile.
authors.affiliation: Zydus Research Centre, Sarkhej-Bavla N.H. 8A Moraiya, Ahmedabad 382210, India; Department of Chemistry, Faculty of Science, M.S. University of Baroda, Vadodara 390002, India. Electronic address: jadavpradeep37@rediffmail.com.
authors.forename: Pradip
authors.initials: P
authors.lastname: Jadav
authors.affiliation: Zydus Research Centre, Sarkhej-Bavla N.H. 8A Moraiya, Ahmedabad 382210, India. Electronic address: rajeshbahekar@zyduscadila.com.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Bahekar
authors.affiliation: Department of Chemistry, Faculty of Science, M.S. University of Baroda, Vadodara 390002, India. Electronic address: shailesh-chem@msubaroda.ac.in.
authors.forename: Shailesh R
authors.initials: SR
authors.lastname: Shah
authors.affiliation: Zydus Research Centre, Sarkhej-Bavla N.H. 8A Moraiya, Ahmedabad 382210, India.
authors.forename: Dipam
authors.initials: D
authors.lastname: Patel
authors.affiliation: Zydus Research Centre, Sarkhej-Bavla N.H. 8A Moraiya, Ahmedabad 382210, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Joharapurkar
authors.affiliation: Zydus Research Centre, Sarkhej-Bavla N.H. 8A Moraiya, Ahmedabad 382210, India.
authors.forename: Mukul
authors.initials: M
authors.lastname: Jain
authors.affiliation: Zydus Research Centre, Sarkhej-Bavla N.H. 8A Moraiya, Ahmedabad 382210, India.
authors.forename: Kalapatapu V V M
authors.initials: KV
authors.lastname: Sairam
authors.affiliation: Zydus Research Centre, Sarkhej-Bavla N.H. 8A Moraiya, Ahmedabad 382210, India.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Singh
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D015394:Molecular Structure; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D010881:Piperidones; D011719:Pyrazines; D014230:Triazoles; D000068900:Sitagliptin Phosphate
keywords: Aminomethyl-piperidones; Antidiabetic; DPP-IV inhibitors; Long-acting; Selective