Antimycobacterial activity of spirooxindolo-pyrrolidine, pyrrolizine and pyrrolothiazole hybrids obtained by a three-component regio- and stereoselective 1,3-dipolar cycloaddition
Antimycobacterial activity of spirooxindolo-pyrrolidine, pyrrolizine and pyrrolothiazole hybrids obtained by a three-component regio- and stereoselective 1,3-dipolar cycloaddition
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DOI：
10.1039/c0md00239a
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发表时间：
2011-07-01
期刊：
影响因子：
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通讯作者：
Sriram, Dharmarajan
中科院分区：
文献类型：
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作者：
Rajesh, Stephen Michael;Perumal, Subbu;Sriram, Dharmarajan
由isatin和苯基甘氨酸/脯氨酸/硫脯氨酸原位合成的-硝基苯乙烯与非稳定的亚甲基酰基化合物进行区域和立体选择性反应，得到了spirooxindolo -吡咯烷、吡咯lizine和吡咯洛噻唑等杂化化合物。对这些化合物的体外抗结核分枝杆菌H37Rv （MTB）活性进行了评价。11个化合物的活性高于吡嗪酰胺，其中6′-（3-硝基苯基）-7′-硝基-3′，6′，7′，7a′-四氢-1′- h -螺-[吲哚-3,5′-吡咯罗-[1,2-c]噻唑]-2- 1的MIC值为7.6 μ M，其效价与一线抗结核药物乙胺丁醇相似，是吡嗪酰胺的6.7倍。
Spirooxindolo-pyrrolidine, pyrrolizine and pyrrolothiazole hybrid compounds were obtained in excellent yields from the regio- and stereoselective reaction between beta-nitrostyrenes and non-stabilized azomethine ylides, generated in situ from isatin and phenylglycine/proline/thiaproline. These compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB). Eleven compounds were more active than pyrazinamide and one of them, namely 6'-(3-nitrophenyl)-7'-nitro-3',6',7',7a'-tetrahydro-1'H-spiro-[indoline-3,5'-pyrrolo-[1,2-c]thiazol]-2-one, displayed a 7.6 mu M MIC value, which represents a potency similar to that of the first-line anti-TB drug ethambutol and 6.7 times higher than that of pyrazinamide.