The analgesic activity of some benzoxazolone derivatives.
The analgesic activity of some benzoxazolone derivatives.
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一些苯并恶唑酮衍生物的镇痛活性。
DOI：
10.1021/ja01172a036
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发表时间：
1949
影响因子：
15
通讯作者：
M. A. Spielman
中科院分区：
文献类型：
--
作者：
W. Close;B. D. Tiffany;M. A. Spielman
Lespagnol和他的同事2是第一个指出苯并恶唑酮类化合物可能影响中枢神经系统的人。由于苯并恶唑酮在结构上与2，4-恶唑烷二酮相关，而2，4-恶唑烷二酮是许多具有镇痛和抗惊厥活性的化合物的核心，3因此似乎需要在苯并恶唑酮衍生物中进行广泛的研究，以获得可能的治疗应用。本研究中包括的化合物是苯并恶唑酮的N-烷基、N-酰基和N-二烷基氨基烷基衍生物以及各种核取代衍生物。发现这些化合物大多数能引起动物轻度镇痛，苯并恶唑酮的制备需要使用各种邻氨基酚（II）作为中间体。这些通常通过硝化相应的苯酚（I），然后催化还原来制备。在某些情况下，认为苯酚与氯化重氮苯偶联并化学还原生成的偶氮衍生物更为有利。大多数氨基酚对空气氧化非常敏感;这些被分离并以其盐酸盐的形式使用。
Lespagnol and his co-workers2 were the first to indicate that compounds of the benzoxazolone type may affect the central nervous system. In-asmuch as benzoxazolone is structurally related to 2, 4-oxazolidinedione which forms the nucleus of a number of compounds with analgesic and an-ticonvulsant activity, 3 it seemed desirable to make an extensive search among benzoxazolone derivatives for possible therapeutic application. The compounds included in this study were N-alkyl, N-acyl, and N-dialkylaminoalkyl derivatives of benzoxazolone and various nuclear sub-stituted derivatives. It was found that a majority of these compounds are capable ofinducing mild analgesia in animals.The preparation of the benzoxazolones required the use of various o-aminophenols (II) as inter-mediates. These were prepared generally through nitration of the corresponding phenol (I), followed by catalytic reduction. In certain cases it was con-sidered more expedient to couple the phenol with benzenediazonium chloride and to reduce the re-sulting azo derivative chemically. Most of the aminophenols were very sensitive to air oxidation; these were isolated and used in the form of their hydrochlorides.