CATALYSTS FOR THE HYDROLYSIS OF COCAINE

描述：(申请人摘要) 这是一项设计和合成一组新化合物的提案， 可以结合可卡因并催化其水解性。预计这些化合物将 无毒，并与可卡因结合并特异性地将其水解性。自.以来 这是一种解决可卡因问题的新方法，各种结构都 提示可卡因可以通过与其苯甲酰基相互作用而结合，其 托烷骨架和它的氮原子。最简单的催化剂 将首先检查准备，但更复杂的结构是 可能对可卡因更有效、更具体。 所提出的催化剂不是蛋白质，而是使用了一些 糖衍生物的部分可卡因结合力。相对较小的 所提出的结构具有“小分子”的药用优势 探员们。应该可以在药物释放库中对它们进行管理， 也可以通过口服和注射的方式给药。因为他们是 不是蛋白质，它们几乎肯定不是抗原性的。就这样重复着 治疗应该是可能的。 拟议的结构利用了校长之前的工作 调查员，其中某些酯，但还没有可卡因， 以14,000,000的速度加速催化水解。它是 提出了为可卡因水解而设计的催化剂，如果他们实现了 这种加速将有助于治疗可卡因成瘾，也将有助于 治疗过量可卡因中毒。 在这项建议中，只有化学研究才能确定 这些在生理条件下对可卡因进行水解的催化剂- 包括添加血清-将被研究。如果有一些非常有效的 催化剂被开发，随后的工作不需要资金 这段时间将专门用于动物和人体试验，以建立 新型催化剂作为治疗可卡因的有用药物 上瘾和可卡因中毒。

DESCRIPTION: (Applicant's Abstract) This is a proposal to design and synthesize a group of novel compounds that can bind cocaine and catalyze its hydrolysis. The compounds are expected to be non-toxic and to bind cocaine and hydrolyze it with specificity. Since this is a novel approach to the cocaine problem, a variety of structures are suggested that can bind cocaine by interacting with its benzoyl group, its tropane skeleton, and its nitrogen atom. The catalysts that are simplest to prepare will be examined first, but the more complicated structures are likely to be more effective and more specific for cocaine. The catalysts proposed are not proteins, but are enzyme mimics using some sugar derivatives for part of their cocaine binding. The relatively small structures proposed have the advantage of "small molecules" as medicinal agents. It should be possible to administer them in drug-release depots, and also to administer them both orally and by injection. Since they are not proteins, they will almost certainly not be antigenic. Thus repeated treatment should be possible. The proposed structures take advantage of previous work of the principal investigator in which certain esters, but not yet cocaine, were catalytically hydrolyzed with rate accelerations of 14,000,000. It is proposed that catalysts designed for cocaine hydrolysis, if they achieve such accelerations, will be useful in treating cocaine addiction and also in treating cocaine intoxication from overdose. In this proposal only the chemical studies to establish the effectiveness of these catalysts in hydrolyzing cocaine under physiological conditions - including with added serum - will be studied. If some highly effective catalysts are developed, subsequent work for which no funds are requested at this time will be devoted to the animal and human trials needed to establish the new catalysts as useful medicinal agents for the treatment of cocaine addiction and cocaine poisoning.