EXPERIMENTAL CHEMOTHERAPY OF TUBERCULOSIS .2. THE SYNTHESIS OF PYRAZINAMIDES AND RELATED COMPOUNDS
EXPERIMENTAL CHEMOTHERAPY OF TUBERCULOSIS .2. THE SYNTHESIS OF PYRAZINAMIDES AND RELATED COMPOUNDS
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DOI：
10.1021/ja01134a045
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发表时间：
1952-01-01
影响因子：
15
通讯作者：
WILLIAMS, JH
中科院分区：
文献类型：
--
作者：
KUSHNER, S;DALALIAN, H;WILLIAMS, JH
本文叙述了大量具有抗结核活性的吡嗪酰胺类化合物及其有关化合物的制备。这些化合物主要是吡嗪酰胺的烷基、芳基、酰基和杂环衍生物。制备了几种相关吡嗪的缩氨基硫脲用于体内试验。在所制备的化合物中，吡嗪酰胺在小鼠试验中的活性高于对氨基水杨酸，并且在人体中被发现具有临床活性。烟酰胺和N-噻唑基烟酰胺的体内抗结核活性已经被我们中的一些人证实，这导致了在与它们密切相关的杂环化合物领域中的进一步合成。尽管在吡嗪化学领域中，已经报道了几种化合物作为兴奋剂、抗糙皮病剂或局部麻醉剂的活性，但据我们所知，还没有吡嗪类化合物在结核病化疗中的研究。由于吡嗪衍生物在结构上类似于环上有一个额外的氮原子取代的烟酰胺，因此确定这种结构上的相似性是否是有意义的，
The preparation of a large number of pyrazinamides and related compounds for antituberculous activity is described. The majority of these compounds were alkyl, aryl, acyl and heterocyclicderivatives of pyrazinamides. Thiosemicarbazones of several related pyrazines were prepared for in vivo testing. Of the compounds prepared, pyrazinamide was found to be more active than^-aminosalicylic acid in the mouse test, and was found to be clinically active in humans.The in vivo antituberculous activity of nicotin-amide and N-thiazolylnicotinamide, which has been reported2 by some of us, led to further synthe-sis in the field of heterocyclics closely related to them. Although in the field of pyrazine chemistry several compounds have been reported to be active as analeptics, 3 antipellagric agents4 or local anesthet-ics, 5 to our knowledge no study of pyrazines has been made in the chemotherapy oftuberculosis. Since thepyrazine derivatives resemble, in struc-ture,’nicotinamide with an additional nitrogen atom substituted in the ring, it was of interest to determine whether or not this similarity in structure