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Pyridine-3-sulphon-(2-pyridyl)-amide; a Note on the Modelling of Chemotherapeutic Agents

 

作者:

 

期刊: Nature  (Nature Available online 1940)
卷期: Volume 146, issue 3707  

页码: 653-654

 

ISSN:0028-0836

 

年代: 1940

 

DOI:10.1038/146653a0

 

出版商: Nature Publishing Group

 

数据来源: Nature

 

摘要:

THIS compound (I) was prepared for the following reason: pyridine-3-sulphonic acid and its amide were found to inhibit bacterial growth, apparently by interference with nicotinic acid metabolism1. Sulphanilamide appears to act as a therapeutic agent by interfering with the utilization ofp-aminobenzoic acid by the invading organisms2, but the 2-aminopyridine derivative(M.&B. 693) is in many cases more effective. Following a rule of thumb method common in chemotherapeutic research, theM.&B. 693 analogue of pyridine-3-sulphonic acid, (I), was prepared and its inhibitory powers compared with those of the parent acid and amide byin vitrotests analogous to those previously described1,2. The compound was found less active than the simple acid and amide.In terms of the theory3 on the basis of which pyridine-3-sulphonic acid was first investigated, which relates several inhibitory compounds to definite structures (for example, p-aminobenzoic acid, nicotinic acid) of importance to the organisms concerned, such failure to produce a more active compound can readily be understood. There is considerable specificity between the mutual effects of p-aminobenzoic acid and sulphanilamide, and between nicotinic acid and pyridine-3-sulphonic acid. M.&B. 693 is possibly related equally specifically to a derivative of £>-aminobenzoic acid. Unless, therefore, the natural nicotinic acid derivatives are similar to those of p-aminobenzoic acid, it is unlikely that a group which enhances the activity of sulphanilamide will enhance that of pyridine-3-sulphonic acid. Instances of failure to produce more active 'hybrids' in this manner are common in chemotherapeutic literature; for example, among sulphanilamide derivatives themselves, diethylaminoalkyl4, quino-line5, tropinone8 and dihydrocuprein9 derivatives are described as of relatively little activity, and hybrids between quinine and emetine7 have not the activity of optimal members of the component series. It is suggested that the reason for such lack of success may be the same as in the case of the present pyridyl compound. Though corresponding essential metabolites are not in these cases known, it is not likely that they will be closely related to one another; known essential metabolites, for example, the vitamins, are very diverse in structure.Preparation of (I). Pyridine-3-sulphonyl chloride (from 2-5 gm. of the acid) and 2-aminopyridine (1-5 gm.; I am indebted to Dr. A. J. Ewins for this material) were mixed in pyridine (5 ml.), warmed at 100° for | hr. and water (20 ml.) added. The product separated on cooling and was recrystallized from alcohol (60 ml.) yielding colourless prisms (1-8 gm.) m.p. 185° (found: C, 50-8; H, 4-0; N, 17-9; S, 13-5 per cen

 

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