Synthesis and PTP1B inhibition of novel 4-aryl-1-oxa-9-thiacyclopenta[b]fluorenes

Authors
Wrobel, J Li, ZA Sredy, J Sawicki, DR Seestaller, L Sullivan, D
Citation
J. Wrobel et al., Synthesis and PTP1B inhibition of novel 4-aryl-1-oxa-9-thiacyclopenta[b]fluorenes, BIOORG MED, 10(14), 2000, pp. 1535-1538
Citations number
12
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
10
Issue
14
Year of publication
2000
Pages
1535 - 1538
Database
ISI
SICI code
0960-894X(20000717)10:14<1535:SAPION>2.0.ZU;2-9
Abstract
Novel 4-aryl-1-oxa-9-thiacyclopenta[b]fluorenes were designed, synthesized, and evaluated as inhibitors of the protein tyrosine phosphatase, PTP1B. Co mpounds 3 (IC50 = 284 nM) and 4 (IC50 = 74 nM), showed nanomolar potency ag ainst PTP1B (TRDI(P)YETD(P)Y(P)YRK as substrate). Compound 4 also lowered i nsulin in the diabetic ob/ob mouse at a dose of 10 mg/kg/day, po. (C) 2000 Elsevier Science Ltd. All rights reserved.