2-Aryl-3,3,3-trifluoro-2-hydroxypropionic acids: a new class of protein tyrosine phosphatase 1B inhibitors.
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.
Adams
David R
DR
Department of Chemistry, School of Engineering & Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK. D.R.Adams@hw.ac.uk
Abraham
Achamma
A
Asano
Jun
J
Breslin
Catherine
C
Dick
Colin A J
CA
Ixkes
Ulrich
U
Johnston
Blair F
BF
Johnston
Derek
D
Kewnay
Justin
J
Mackay
Simon P
SP
MacKenzie
Simon J
SJ
McFarlane
Morag
M
Mitchell
Lee
L
Spinks
Daniel
D
Takano
Yasuo
Y
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
D004791:Enzyme Inhibitors; D008024:Ligands; D011422:Propionates; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1