FUNCTIONALIZED CONGENERS OF BIOACTIVE COMPOUNDS

我们实验室最近的研究表明，某些药物可能是 附着在定义明确的“载体”分子上，并且仍然保持着 结合受体部位并影响生物活性。这 将药物附着在载体上的合成策略称为 “功能化同类”方法。“载体”分子可以是许多 比母药大几倍；事实上，实际上没有最大 全功能模拟的大小限制。与前药方法不同 或将药物固定化为缓释，即“功能化” 同类“的方法旨在产生没有代谢作用的类似物 裂解步骤是激活所必需的。此外，依附于 药物到诸如多肽之类的“载体”可产生增强的亲和力 在细胞外受体位置上，以及在 母体药物的药理概况。 含有连接链的嘌呤衍生物被开发为 腺苷受体和三磷酸腺苷受体的功能化同系物。 荧光染料等报告基团已经共价连接 从而得到亲和力相对较高的受体探针。网站： 替伦西平(中国常用药物)结构的链衍生化 治疗胃溃疡和作为大脑的研究工具)，一种选择性 毒碱拮抗剂已经被找到了。在一系列氨基烷基中 结果表明，随着链长的增加，分子间的相互作用增强 该衍生物作为毒碱拮抗剂的效力。成立为法团 异硫氰酸苯酯的化学反应亲和标记 对于毒碱受体已被开发出来。其他记者团体包括 在telenzepine系列中包括生物素，对氨基苯乙酰(for 制备放射性示踪剂和光亲和标记试剂)，以及 荧光染料荧光素和四甲基罗丹明(用于定位 在显微镜下观察受体位置，并进行不需要的结合分析 放射性同位素的使用)。

Recent work in our laboratory has demonstrated that certain drugs may be attached to well-defined "carrier" molecules and still retain the ability to bind to the receptor site and effect biological activity. This synthetic strategy for the attachment of drugs to carriers is termed the "functionalized congener" approach. The "carrier" molecule may be many times larger than the parent drug; indeed there is practically no maximum size limitation for a fully potent analog. Unlike the prodrug approach or the immobilization of drugs for slow release, the "functionalized congener" approach is designed to produce analogs for which no metabolic cleavage step is necessary for activation. Moreover, the attachment of the drug to a "carrier" such as a peptide may result in enhanced affinity at an extracellular receptor site and an improvement in the pharmacological profile of the parent drug. Purine derivatives containing attached chains were developed as functionalized congeners for adenosine receptors and for ATP receptors. Reporter groups such as fluorescent dyes have been covalently attached resulting in receptor probes of relatively high affinity. Sites for chain derivatization on the structures of telenzepine (useful drugs in treating stomach ulcers and as research tools for the brain), a selective muscarinic antagonists, have been located. In a series of amino alkyl derivatives, it was found that increasing the chain length enhances the potency of the derivative as a muscarinic antagonist. By incorporation of a phenyl isothio-cyanate group, chemically reactive affinity labels for muscarinic receptors were developed. Other reporter groups included in the telenzepine series include biotin, p-aminophenylacetyl (for preparing radiotracers and photoaffinity labeling reagents), and fluorescent dyes fluorescein and tetramethylrhodamine (for locating the receptor sites microscopically and for binding assays that do not require the use of radioisotopes).