PHOTOCHEMISTRY OF DIAZENIUMDIOLATES--NO RELEASING DRUGS

二醇二氮烯鎓盐的光化学——无释放药物

• 批准号: 6525463
• 负责人: John P Toscano
• 金额: $ 18.59万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6525463
• 关键词: chemical synthesis; computer simulation; diazo compound; drug design /synthesis /production; electron spin resonance spectroscopy; infrared spectrometry; nitrene; nitric oxide; photochemistry

DESCRIPTION (Adapted from abstract): Nitric oxide (NO) is an important bioregulator that is involved in the control of neurotransmission, blood clotting, and blood pressure. In addition, NO has been shown to kill cancerous tumor cells. Thus, previous research has focused on developing drugs that can deliver NO efficiently and selectively, e.g., to tumor cells without dramatically affecting other bioregulatory processes. Diazeniumdiolates are an interesting class of such drugs presently under development. Recent efforts to make diazeniumdiolates more effective pharmaceuticals have concentrated on using derivatives of such compounds to deliver NO specifically to a targeted site. A major goal of the proposed research is to develop photochemical precursors to diazeniumdiolates that can be used as effective NO-releasing agents. Since initial experiments in other laboratories with classic photoprotecting groups gave unexpected and disappointing results, reaction pathways will be clarified so that more efficient phototriggered NO-releasing drugs can be rationally designed. In addition, if diazeniumdiolates are to enjoy routine medical use, their basic photochemistry must be understood so that phototoxicity issues may be anticipated and avoided The specific aims of the proposed research, which address the above goals, are briefly outlined: (1) Reaction pathways involved in the photochemistry of O-alkylated diazeniumdiolates will be elucidated with product analysis and the powerful tool of time-resolved infrared (TRIR) spectroscopy. (2) Oxygen-substituted nitrenes (O-nitrenes), proposed to be intermediates efficiently produced by photolysis of O-alkylated diazeniumdiolates will be characterized. (3) Since O-nitrenes are a heretofore unstudied class of intermediates their reactivity will be examined in detail by both experimental and computational methods. (4) Ultimately, new O-alkylated diazeniumdiolate derivatives for the efficient photochemical production of NO will be designed and tested.

描述（改编自摘要）：一氧化氮 (NO) 是一种重要的 生物调节剂参与神经传递、血液的控制 凝血和血压。 此外，NO已被证明可以杀死 癌性肿瘤细胞。 因此，之前的研究主要集中在开发 能够有效、选择性地将 NO 递送至肿瘤细胞等的药物 不会显着影响其他生物调节过程。 二氮烯鎓二醇是目前正在研究的一类有趣的药物 发展。 最近为使二醇二氮烯鎓盐成为更有效的药物而做出的努力 专注于使用此类化合物的衍生物来传递 NO 专门针对目标站点。 拟议研究的一个主要目标是 开发二氮烯鎓二醇的光化学前体，可用作 有效的NO释放剂。 由于在其他方面进行了初步实验 具有经典光保护基团的实验室给出了意想不到的和 令人失望的结果，反应途径将得到澄清，以便更多 可以合理设计高效的光触发NO释放药物。 在 此外，如果二醇二氮烯鎓要享受常规医疗用途，它们的基本 必须了解光化学，以便解决光毒性问题 预期和避免的 针对上述目标的拟议研究的具体目标， 简要概述： (1) 光化学涉及的反应途径 O-烷基化二氮烯二醇盐的含量将通过产品分析来阐明 以及时间分辨红外 (TRIR) 光谱的强大工具。 (2) 氧取代氮烯（O-氮烯），建议作为中间体 通过 O-烷基化二醇二氮烯鎓盐的光解有效生产 特点。 (3) 由于邻氮宾是迄今为止尚未研究过的一类 中间体的反应性将由双方详细检查 实验和计算方法。 (4)最终，新的O-烷基化 用于高效光化学生产的二氮烯鎓二醇衍生物 NO 将被设计和测试。

项目成果

Controlled photochemical release of nitric oxide from O(2)-naphthylmethyl- and O(2)-naphthylallyl-substituted diazeniumdiolates.

• DOI: 10.1021/ja027957h
• 发表时间: 2002-10
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: K. Bushan;Hua Xu;P. Ruane;R. D’Sa;Christopher M. Pavlos;Joseph A. Smith;Tevye C. Celius;J. Toscano

Controlled photochemical release of nitric oxide from O2-benzyl-substituted diazeniumdiolates.

• DOI: 10.1021/ja026900s
• 发表时间: 2002-07
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: P. Ruane;Bushan Km;Christopher M. Pavlos;R. D’Sa;J. Toscano