PYRROLE BASED APPROACH TO RIGIDIN AND RELATED ALKALOIDS

基于吡咯的刚性蛋白和相关生物碱的方法

• 批准号: 2110861
• 负责人: JOHN T. GUPTON
• 金额: $ 9.81万
• 依托单位: UNIVERSITY OF NORTH CAROLINA ASHEVILLE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2110861
• 关键词: alkaloids; analog; biological products; calmodulin; chemical substitution; drug design /synthesis /production; drug screening /evaluation; inhibitor /antagonist; phosphodiesterase inhibitors; pyrroles

DESCRIPTION: The principal investigator notes that in recent years he has been actively involved in developing efficient and regiocontrolled syntheses for pyrrole containing substances which have subsequently been bioassayed as part of the National Cancer Institute's in vitro screening program and that these synthetic methods have been based on the condensation reactions of vinylogous iminium salt derivatives with alpha-aminocarbonyl compounds. He indicates that as part of this program, he is currently directing his efforts towards a new and novel, marine derived alkaloid, Rigidin which has been shown to be a significant inhibitor of Calmodulin activated phosphodiesterase, a possible chemotherapeutic target. In this proposal he states that he seeks to accomplish at least four things: 1. extend the chemistry that he has developed for the regiocontrolled preparation of disubstituted pyrroles to the synthesis of trisubstituted pyrroles. 2. carry out appropriate experiments to understand the controlling features for the formation of trisubstituted pyrroles from a variety of vinylogous iminium salt derivatives. 3. to begin to apply this chemistry to the synthesis of the novel, Calmodulin antagonist Rigidin and related substances such as the bioactive, natural product Polycitone A. 4. to continue to submit samples of Rigidin and Polycitone A analogs, precursors and related pyrrole containing compounds to the NCI for further biological evaluation as part of the in vitro, primary antitumor screening program.

主要研究人员指出，近年来，他 一直积极参与开发高效和区域控制的合成 对于含吡咯的物质，随后已进行生物测定， 国家癌症研究所体外筛查项目的一部分， 这些合成方法基于以下物质的缩合反应： 乙烯基亚胺鎓盐与α-氨基羰基化合物的衍生物。 他 作为该计划的一部分，他目前正在指导他的 致力于一种新的和新颖的，海洋衍生的生物碱，Rigidin， 被证明是钙调素激活的重要抑制剂 磷酸二酯酶，可能的化疗靶点。 在这份提案中，他 他说，他至少要做四件事：1。 延长 化学，他已经开发了区域控制制备， 二取代的吡咯到三取代的吡咯的合成。 2. 进行适当的实验，以了解控制功能， 由各种乙烯基化合物形成三取代吡咯 亚胺盐衍生物。 3. to开始to apply应用this chemistry化学to the 新型钙调素拮抗剂Rigidin及其相关物质的合成 例如生物活性的天然产物Polycitone A。4. 继续 提交Rigidin和Polycitone A类似物、前体和相关样品 含吡咯的化合物提交给NCI进行进一步的生物学评价， 体外初步抗肿瘤筛选计划的一部分。