| Autor: |
Thomas AA; Array BioPharma Inc., 3200 Walnut Street, Boulder, CO 80301, USA. athomas@arraybiopharma.com, De Meese J, Le Huerou Y, Boyd SA, Romoff TT, Gonzales SS, Gunawardana I, Kaplan T, Sullivan F, Condroski K, Lyssikatos JP, Aicher TD, Ballard J, Bernat B, DeWolf W, Han M, Lemieux C, Smith D, Weiler S, Wright SK, Vigers G, Brandhuber B |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2008 Jan 15; Vol. 18 (2), pp. 509-12. Date of Electronic Publication: 2007 Dec 03. |
| DOI: |
10.1016/j.bmcl.2007.11.098 |
| Abstrakt: |
Inhibition of the thiamine-utilizing enzyme transketolase (TK) has been linked with diminished tumor cell proliferation. Most thiamine antagonists have a permanent positive charge on the B-ring, and it has been suggested that this charge is required for diphosphorylation by thiamine pyrophosphokinase (TPPK) and binding to TK. We sought to make neutral thiazolium replacements that would be substrates for TPPK, while not necessarily needing thiamine transporters (ThTr1 and ThTr2) for cell penetration. The synthesis, SAR, and structure-based rationale for highly potent non-thiazolium TK antagonists are presented. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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