Synthesis and antituberculosis activity of novel 5-styryl-4-(hetero)aryl-pyrimidines via combination of the Pd-catalyzed Suzuki cross-coupling and S_N^H reactions

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• 作者：Marionella A. Kravchenko^a ; Egor V. Verbitskiy^b ; ^c ; ^{Verbitsky@ios.uran.ru" class="auth_mail} ; Igor D. Medvinskiy^a ; Gennady L. Rusinov^b ; ^c ; Valery N. Charushin^b ; ^c
• 关键词：SJYFTSNWNGUCJI-JLHYYAGUSA-N ; HSMXDGKBNZEYPQ-CMDGGOBGSA-N ; SRNGBYZODBSPKN-VAWYXSNFSA-N ; BNFCWKVJNRZFPQ-CMDGGOBGSA-N ; MHONRMDDOBZALO-CMDGGOBGSA-N ; NZSKSUXYPVHLKR-JLHYYAGUSA-N ; ZBTHZGHKQUAWBM-DTQAZKPQSA-N ; ZTPYWTXTZNYBTO-JLHYYAGUSA-N
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：15 July 2014
• 年：2014
• 卷：24
• 期：14
• 页码：3118-3120
• 全文大小：551 K

文摘

Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (S_N^H) reactions proved to be a convenient method for the synthesis of 5-styryl-4-(hetero)aryl substituted pyrimidines from commercially available 5-bromopyrimidine. All intermediate 5-bromo-4-(hetero)aryl substituted pyrimidines and also the targeted 5-styryl-4-(hetero)arylpyrimidines were found to be active in micromolar concentrations in vitro against Mycobacterium tuberculosis H₃₇Rv, avium, terrae, and multi-drug-resistant strain isolated from tuberculosis patients in Ural region (Russia). It has been found that some of these compounds possess a low toxicity and have a bacteriostatic effect, comparable and even higher with that of first-line antituberculosis drugs.