Mahboobi, Siavosh and Uecker, Andrea and Cenac, Christophe and Sellmer, Andreas and Eichhorn, Emerich and Elz, Sigurd and Boehmer, Frank-D. and Dove, Stefan (2007) Inhibition of FLT3 and PDGFR tyrosine kinase activity by bis(benzo[b]furan-2-yl)methanones. BIOORGANIC & MEDICINAL CHEMISTRY, 15 (5). pp. 2187-2197. ISSN 0968-0896,
Full text not available from this repository. (Request a copy)Abstract
series of bis(benzo[b]furan-2-yl)methanones was synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. Mostly, C-5 substitution leads to PDGFR selectivity, which was strongest in the case of the 5,5'-dimethoxy derivative. The 5.5'-diamino and the 6,6'-dihydroxy compounds are more active at FLT3. At both kinases, the potency of the best inhibitors approaches IC50 values of ca. 0.5 mu M. Molecular modeling studies suggest that the bisbenzofuranylmethanones are able to fit into the same binding site as their indolyl analogues which have been suggested to form a bidentate hydrogen bridge with the backbone in the hinge regions. The loss of one H bond by the NH-O exchange might be partially compensated by, for example, the weak interaction of one furanyl oxygen with FLT3 Cys-828. (c) 2007 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACUTE MYELOID-LEUKEMIA; NORMAL HEMATOPOIESIS; ANTIVIRAL ACTIVITY; POTENT; DERIVATIVES; ANGIOGENESIS; DISEASE; TARGETS; DOMAIN; ACIDS; bisbenzofuranylmethanone; receptor tyrosine kinase; FLT3; PDGFR; bisindolymethanone; benzofuranylindolylmethanone |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry I (Prof. Elz) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Dec 2020 08:10 |
| Last Modified: | 21 Dec 2020 08:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33054 |
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