A chiral optical amide substituted α,β-diamino acid derivative and its preparation method and application

Abstract

The invention discloses an α,β-diamino acid derivative substituted by a chiral optical pure alkyne amide, a preparation method and an application thereof. The structure of the derivative is shown in formula (I); wherein, the R 1 For benzene, naphthyl, halogenated phenyl, C 1～4 Alkyl substituted phenyl, C 1～4 Alkoxy substituted phenyl; R 2 is hydrogen, halogen, C 1～2 Alkyl, C 1～2 Alkoxy or tert-butylcarbonyl substituted C 1～4 Alkoxy; R 3 is thiophene, furan, naphthyl, benzene, halophenyl, methyl-substituted phenyl or methoxy-substituted phenyl; R 4 for hydrogen, C 1～2 Alkyl or phenyl. The compound is novel in structure and has good antitumor effect, especially has good effect on human colon cancer, human non-small cell lung cancer, human osteosarcoma and human acute promyelocytic leukemia, and has great antitumor effect. Great application value; at the same time, the preparation method has few reaction steps, simple and safe operation, low cost, and has the advantages of high atom economy, high selectivity and high yield.

Description

technical field [0001] The present invention relates to the technical field of pharmaceutical synthesis and anticancer drugs, and more specifically relates to a chiral optical alkyne amide substituted α,β-diamino acid derivative and its preparation method and application. Background technique [0002] Carbon atom chiral centers and amide groups widely exist in natural products and some common drugs, which have good activity, for example, in some antibacterial drugs such as quinolone antibacterial drugs and blood lipid-lowering drugs such as statins Both contain chiral centers of carbon atoms, but the chiral centers of carbon atoms are particularly important for drug activity. The effects of different isomers can vary thousands of miles, such as the "reaction stop" event that occurred in the last century. However, the aryl all-carbon chiral center and amide are the ubiquitous structural units in natural products and medicines. Compounds with these two structures have good bio...

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Problems solved by technology

However, the aryl all-carbon chiral center and amide are the ubiquitous structural units in natural products and medicines. Compounds with these two structures have good biological activity and have great development prospects in antitumor aspects; in addition, alkyne Amide groups also widely exist in anticancer, antibacterial, anti-inflammatory drugs and many natural products, such as steroidal anti-inflammatory drugs, sulfonamide antibacterial drugs, etc.; but chiral optical alkyneamide substituted α,β- In the chemical synthesis of diamino acid derivatives, an amide compound containing two aryl all-carbon chiral centers is generated, so how to construct an alkyne amide compound with two all-carbon chiral centers with high purity , and at the same time ensure its good activity, relatively speaking, there are still some challenges

[0003] In the early stage of research, a class of α-aryl-α, β-diamino acid ester derivatives (patent 201710004520.3) was synthesized. SMMC7721 cells) have a good inhibitory effect, but the types and activity range of the compound still have great research value and development space, which needs further research

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