| Autor: |
Vedantham P; Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045, USA., Zhang M, Gor PJ, Huang M, Georg GI, Lushington GH, Mitscher LA, Ye QZ, Hanson PR |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of combinatorial chemistry [J Comb Chem] 2008 Mar-Apr; Vol. 10 (2), pp. 195-203. Date of Electronic Publication: 2007 Dec 29. |
| DOI: |
10.1021/cc7000869 |
| Abstrakt: |
Efforts to synthesize potential methionine aminopeptidase inhibitors is described. Preliminary SAR and docking studies served as a guide to design the compound libraries. "Chromatography-free" synthesis of various heterocyclic amides was realized by using a high-load, soluble coupling reagent derived via ring-opening metathesis polymerization (ROMP). Subsequent microwave-assisted Suzuki reactions with ortho-substituted arylboronic acids, followed by chromatographic purification afforded a 55-member library in high yields and purities. While the biological testing was not satisfactory, concurrent X-ray crystallography studies revealed key structural features essential for inhibition of methionine aminopeptidase, which directed fruitful results reported in the accompanying manuscript. In addition, in silico Lipinksi profiles and ADME properties of the library are also reported. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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