| Autor: |
Dolle RE; Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals Ltd., The Frythe, Welwyn, Hertfordshire, U.K., McNair D, Hughes MJ, Kruse LI, Eggelston D, Saxty BA, Wells TN, Groot PH |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1992 Dec 25; Vol. 35 (26), pp. 4875-84. |
| DOI: |
10.1021/jm00104a014 |
| Abstrakt: |
Citric acid analogues (+/-)-12a,b and (+/-)-17a,b, where one of the primary carboxylates has been replaced by a sulfoximinoyl and a 3-(3-hydroxy-beta-lactamyl) moiety, respectively, have been synthesized and evaluated as inhibitors of ATP-citrate lyase. The design of these inhibitors was based on methionine sulfoximine and tabtoxinine beta-lactam, potent, tight-binding inhibitors of glutamine synthetase. Both ATP-citrate lyase and glutamine synthetase employ phosphate-carboxylate anhydrides as a method for carboxylate activation during catalysis. Only one diastereomer, (+/-)-12a, displayed weak, reversible inhibition, while the remaining citrate analogues (+/-)-12b and (+/-)-17a,b were inactive against the lyase. No time-dependent inactivation of the enzyme was observed. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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