title: 2-Aryl-3,3,3-trifluoro-2-hydroxypropionic acids: a new class of protein tyrosine phosphatase 1B inhibitors.
abstract: A new series of non-peptidic, mono-acid protein tyrosine phosphatase 1B (PTP1B) inhibitors has been identified by structure-based design. Compounds with 2-(indol-3-yl)- and 2-phenyl-3,3,3-trifluoro-2-hydroxypropionic acid core units targeted at the enzyme's primary site and a hydrophobic chlorophenylthiazole extension in its 2 degrees site exhibit 3-60microM IC(50)s for PTP1B inhibition in an Sf9 cell-based assay.
authors.affiliation: Department of Chemistry, School of Engineering & Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK. D.R.Adams@hw.ac.uk
authors.forename: David R
authors.initials: DR
authors.lastname: Adams
authors.forename: Achamma
authors.initials: A
authors.lastname: Abraham
authors.forename: Jun
authors.initials: J
authors.lastname: Asano
authors.forename: Catherine
authors.initials: C
authors.lastname: Breslin
authors.forename: Colin A J
authors.initials: CA
authors.lastname: Dick
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ixkes
authors.forename: Blair F
authors.initials: BF
authors.lastname: Johnston
authors.forename: Derek
authors.initials: D
authors.lastname: Johnston
authors.forename: Justin
authors.initials: J
authors.lastname: Kewnay
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mackay
authors.forename: Simon J
authors.initials: SJ
authors.lastname: MacKenzie
authors.forename: Morag
authors.initials: M
authors.lastname: McFarlane
authors.forename: Lee
authors.initials: L
authors.lastname: Mitchell
authors.forename: Daniel
authors.initials: D
authors.lastname: Spinks
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000145:classification / Q000378:metabolism; D008024:Ligands; D011422:Propionates / Q000737:chemistry* / Q000145:classification* / Q000494:pharmacology; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018411:Spodoptera / Q000166:cytology
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D011422:Propionates; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1