6-cyclohexyl methyl pyrimidone compounds (s-DACOs) non-nucleoside reverse transcriptase inhibitors (nnrtis) as well as preparation method and use thereof

Abstract

The invention relates to 6-cyclohexyl methyl pyrimidone compounds (S-DACOs) non-nucleoside reverse transcriptase inhibitors (NNRTIs) as well as a preparation method and use thereof, belonging to the technical fields of chemical synthesis and medicine. The compounds are 5-alkyl-6-cyclohexylmethyl-2-(4'-carboxylate benzyl)thio-pyrimidone compounds as shown in a formula I, pharmacologically acceptable salts of the 5-alkyl-6-cyclohexylmethyl-2-(4'-carboxylate benzyl)thio-pyrimidone compounds, or precursors and derivatives having the same biological functions; the formula I is shown in the description, wherein R1 is alkyl or cycloalkyl of C1-C6; R2 is alkyl or cycloalkyl of C1-C8, mono-substituted or poly-substituted phenyl, and the substituent group on a benzene ring of the phenyl is hydrogen, halogen, nitro, amino, cyano, sulfonic group, carboxy, alkyl of C1-C3 or alkoxy of C1-C3; R2 is 1-naphthyl, 2-naphthyl, diphenyl, 2-thienyl or a group shown in the description, and in the group shown in the description, X is hydrogen, halogen, nitro, amino, cyano, sulfonic group, carboxy, alkyl of C1-C3 or alkoxy of C1-C3; the chemical formula of R2 is shown in the description; the NNRTIs are obtained by enabling 5-alkyl- 6-cyclohexylmethyl-thiouracil A, which is taken as a raw material, to react with 4-carboxyester benzyl bromide B respectively under the solvent condition and alkaline condition. The compounds provided by the invention have good human immunodeficiency virus (HIV)-1 inhibition activity and low in toxicity, and can be used for preparing medicines for treating acquired immune deficiency syndrome (AIDS).

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis and medicine. Background technique [0002] Acquired immunodeficiency syndrome (AIDS), also known as AIDS, is a disease caused by human immunodeficiency virus (Human immunodeficiency virus, HIV) infection. HIV virus can selectively attack human T lymphocytes and destroy human body The immune system is weakened, making the human body susceptible to infection by external germs, and in severe cases, it can also cause malignant tumors, so the fatality rate is high. [0003] In the viral replication cycle of HIV, reverse transcriptase (Reverse transcriptase, RT) acts on the early stage of its replication and is the key enzyme that catalyzes the conversion of viral RNA to DNA. Therefore, HIV RT has become one of the important targets for the design of anti-HIV drugs . HIV reverse transcriptase inhibitors can be divided into nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleos...

AI Technical Summary

Problems solved by technology

However, nucleoside reverse transcriptase inhibitors (NRTIs) are competitive inhibitors. In addition to inhibiting the replication of viral genes, they also interfere with the growth of DNA chains in normal cells, thereby causing some toxic side effects in the human body.

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