Monocyclic thiophenes as protein tyrosine phosphatase 1B inhibitors: capturing interactions with Asp48.
A series of monocyclic thiophenes was designed and synthesized as PTP1B inhibitors. Guided by X-ray co-crystal structural information and computational modeling, rational design led to key interactions with Asp48 and improved inhibitory potency against PTP1B.
Wan
Zhao-Kui
ZK
Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
Lee
Jinbo
J
Xu
Weixin
W
Erbe
David V
DV
Joseph-McCarthy
Diane
D
Follows
Bruce C
BC
Zhang
Yan-Ling
YL
D001224:Aspartic Acid / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013876:Thiophenes; D001224:Aspartic Acid; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases