title: Structure based design of a series of potent and selective non peptidic PTP-1B inhibitors.
abstract: A series of benzotriazole phenyldifluoromethylphosphonic acids were found to be potent PTP-1B inhibitors. Molecular modeling on the X-ray crystal structure of the lead structure led to the design of potent PTP-1B inhibitors that show moderate selectivity against TC-PTP, a very closely related protein tyrosine phosphatase.
authors.affiliation: Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Quebec H9R 4P8, Canada. lau@merck.com
authors.forename: Cheuk K
authors.initials: CK
authors.lastname: Lau
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Bayly
authors.forename: Jacques Yves
authors.initials: JY
authors.lastname: Gauthier
authors.forename: Chun Sing
authors.initials: CS
authors.lastname: Li
authors.forename: Michel
authors.initials: M
authors.lastname: Therien
authors.forename: Ernest
authors.initials: E
authors.lastname: Asante-Appiah
authors.forename: Wanda
authors.initials: W
authors.lastname: Cromlish
authors.forename: Yves
authors.initials: Y
authors.lastname: Boie
authors.forename: Farnaz
authors.initials: F
authors.lastname: Forghani
authors.forename: Sylvie
authors.initials: S
authors.lastname: Desmarais
authors.forename: Qingping
authors.initials: Q
authors.lastname: Wang
authors.forename: Kathryn
authors.initials: K
authors.lastname: Skorey
authors.forename: Deena
authors.initials: D
authors.lastname: Waddleton
authors.forename: Paul
authors.initials: P
authors.lastname: Payette
authors.forename: Chidambaram
authors.initials: C
authors.lastname: Ramachandran
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kennedy
authors.forename: Giovana
authors.initials: G
authors.lastname: Scapin
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007313:Insecta; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; C032627:methylphosphonic acid; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516609:Ptpn1 protein, mouse