title: Discovery of potent, selective and orally bioavailable triaryl-sulfonamide based PTP1B inhibitors.
abstract: A novel series of pTyr mimetics containing triaryl-sulfonamide derivatives (5a-r) are reported as potent and selective PTP1B inhibitors. Some of the test compounds (5o and 5p) showed excellent selectivity towards PTP1B over various PTPs, including TCPTP (in vitro). The lead compound 5o showed potent antidiabetic activity (in vivo), along with improved pharmacokinetic profile. These preliminary results confirm discovery of highly potent and selective PTP1B inhibitors for the treatment of T2DM.
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. dipam.patel@rediffmail.com
authors.forename: Dipam
authors.initials: D
authors.lastname: Patel
authors.forename: Mukul
authors.initials: M
authors.lastname: Jain
authors.forename: Shailesh R
authors.initials: SR
authors.lastname: Shah
authors.forename: Rajesh
authors.initials: R
authors.lastname: Bahekar
authors.forename: Pradip
authors.initials: P
authors.lastname: Jadav
authors.forename: Amit
authors.initials: A
authors.lastname: Joharapurkar
authors.forename: Nirav
authors.initials: N
authors.lastname: Dhanesha
authors.forename: Mubeen
authors.initials: M
authors.lastname: Shaikh
authors.forename: Kalapatapu V V M
authors.initials: KV
authors.lastname: Sairam
authors.forename: Prashant
authors.initials: P
authors.lastname: Kapadnis
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003920:Diabetes Mellitus / Q000188:drug therapy*; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D013449:Sulfonamides; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse