Application of carbamic acid alkannin ester to preparation of pyruvate kinase inhibitor

Abstract

The invention provides an inhibitor for pyruvate kinase M2 (PKM2), namely a carbamic acid alkannin ester compound. A pyruvate kinase M2 inhibitor which has been reported at present comprises Compound 3, but the invention discovers that the effect of carbamic acid alkannin ester on the inhibition of the PKM2 is higher than that of the Compound 3. Therefore, the carbamic acid alkannin ester serving as an inhibitor for pyruvic acid has important application value. The invention has the advantages that: a novel pyruvate kinase inhibitor, namely the carbamic acid alkannin ester is provided, so that the basis is provided for the screening of novel medicines; and the inhibitor has an important application prospect.

Description

(1) Technical field [0001] The present invention mainly relates to the application of shikonin carbamate in the preparation of pyruvate kinase inhibitors. (2) Background technology [0002] The shikonin carbamate involved in the present invention is an artificially synthesized naphthoquinone compound. For the synthesis method, see Chinese patent CN200910153139.9. [0003] Pyruvate kinase is a key rate-limiting enzyme in glycolysis and plays a key role in energy metabolism. The M2-type pyruvate kinase (PKM2 for short) involved in the present invention mainly exists in the early development of individuals and tumor tissues. There are few PKM2 inhibitors reported so far, among which small molecule compound inhibitors are only one case of compound 3 (Vander Heiden MG, Christofk HR, Schuman E, Subtelny AO, Sharfi H, Harlow EE et al. Biochem Pharmacol2010, 79, 1118) , the amount of which inhibits 50% of the enzyme activity (ie IC50) is 50 μM. [0004] So far, there is no report...

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[0004] So far, there is no report of shikonin carbamate inhibiting pyruvate kinase activity

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