Investigation of 4-amino-5-alkynylpyrimidine-2(1H)-ones as anti-mycobacterial agents

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• 作者：Gaurav Garg^a ; Milind Pande^b ; Ambika Agrawal^c ; Jie Li^d ; Rakesh Kumar^c ; ^{rkumar@ualberta.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tuberculosis ; Heterocycles ; Pyrimidines ; Anti-mycobacterial agent
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：24
• 期：8
• 页码：1771-1777
• 全文大小：914 K

文摘

In vitro anti-mycobacterial activities of novel 4-amino-5-alkynylpyrimidine-2(1H)-ones were investigated. 4-Amino-5-heptynylpyrimidine-2(1H)-one (3) and 4-amino-5-(2-phenylethynyl)pyrimidine-2(1H)-one (7) displayed potent in vitro activity against Mycobacterium bovis and Mycobacterium tuberculosis. Compounds 3 and 7 were also assessed for their in vivo activity in BALB/c mice infected with M. tuberculosis (H37Ra). Both compounds showed promising in vivo efficacy at a dose of 25 mg/kg for 2 weeks. Importantly, compounds 3 and 7 interacted synergistically with the front-line anti-tuberculosis drug isoniazid in vitro and in vivo. These results suggest that this class of compounds has strong anti-mycobacterial potential.