Click-based synthesis and antitubercular evaluation of novel dibenzo[b,d]thiophene-1,2,3-triazoles with piperidine, piperazine, morpholine and thiomorpholine appendages

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• 作者：Lokesh Pulipati^a ; Perumal Yogeeswari^b ; Dharmarajan Sriram^b ; Srinivas Kantevari^a ; ^c ; ^{kantevari@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; ^{kantevari@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Dibenzothiophene ; Triazole ; Piperidine ; Piperazine ; Antitubercular agents ; Click chemistry
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 June 2016
• 年：2016
• 卷：26
• 期：11
• 页码：2649-2654
• 全文大小：1258 K

文摘

A series of novel piperidine, piperazine, morpholine and thiomorpholine appended dibenzo[b,d]thiophene-1,2,3-triazoles were designed and synthesized utilizing azide–alkyne click chemistry in the penultimate step. The required azide building block class="boldFont">6a–class="boldFont">e was synthesized from commercial dibenzo[b,d]thiophene in good yields following five step reaction sequence. All the new analogues class="boldFont">8a–class="boldFont">f, class="boldFont">9a–class="boldFont">f, class="boldFont">10a–class="boldFont">f, class="boldFont">11a–class="boldFont">f & class="boldFont">12a–class="boldFont">f were characterized by their NMR and mass spectral analysis. Screening all thirty new compounds for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, resulted class="boldFont">8a, class="boldFont">8f and class="boldFont">11e as potent analogues with MIC 0.78 μg/mL, 0.78 μg/mL & 1.56 μg/mL, respectively, and has shown lower cytotoxicity. Interestingly, all six piperazine appended dibenzo[b,d]thiophene-1,2,3-triazoles class="boldFont">11a–class="boldFont">f exhibited Mtb inhibition activity with MIC 1.56–12.5 μg/mL. To some extent, the data observed here indicated Mycobacterium tuberculosis inhibition among the appendages is in the order, piperazine > thiomorpholine > morpholine.