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“方法的目的是产生类似的产品，而不是 代谢裂解步骤是激活所必需的。此外， 药物与多肽等“载体”的结合可导致 增强细胞外受体位点的亲和力和改善 在母体药物的药理档案中。 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： 三磷酸腺苷和选择性毒扁豆碱结构的链衍生化 已经找到了敌手。A3腺苷受体在 中枢神经系统、心脏、炎症和生殖功能的调节。 我们已经为这种新型受体开发了唯一的选择性试剂。 选择性A3激动剂对治疗神经退行性变有效 疾病。拮抗剂被认为具有抗炎作用。 属性。新的黄嘌呤和腺苷衍生物正在被 合成，筛选A3受体选择性，然后在 活着。不可逆结合的受体探针正在开发中。

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 ATP and selective muscarinic antagonists have been located. A3 adenosine receptors are important in the regulation of CNS, cardiac, inflammatory, and reproductive functions. We have developed the only selective agents for this novel receptor. Selective A3 agonists are effective in the treatment of neurodegenerative diseases. Antagonists have been proposed to have anti-inflammatory properties. New xanthine and adenosine derivatives are being synthesized, screened for A3-receptor selectivity, and later tested in vivo. Irreversibly-binding receptor probes are being developed.