title: Monocyclic thiophenes as protein tyrosine phosphatase 1B inhibitors: capturing interactions with Asp48.
abstract: 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.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
authors.forename: Zhao-Kui
authors.initials: ZK
authors.lastname: Wan
authors.forename: Jinbo
authors.initials: J
authors.lastname: Lee
authors.forename: Weixin
authors.initials: W
authors.lastname: Xu
authors.forename: David V
authors.initials: DV
authors.lastname: Erbe
authors.forename: Diane
authors.initials: D
authors.lastname: Joseph-McCarthy
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Follows
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Zhang
mesh_terms: 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*
chemical_list: D004791:Enzyme Inhibitors; D013876:Thiophenes; D001224:Aspartic Acid; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases