2-methyl-5-propan-2-yl-2H-pyrrole

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-methyl-5-propan-2-yl-2H-pyrrole
• 化学式: C₈H₁₃N
• 分子量: 123.2
• InChiKey: VPXALMHWAIHEIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  12.4
• 氢给体数：
  0
• 氢受体数：
  1

文献信息

• NOVEL METHOD AND APPLICATION OF UNSYMMETRICALLY MESO-SUBSTITUTED PORPHYRINS AND CHLORINS FOR PDT
  申请人：biolitec Unternehmensbeteiligungs II AG

  公开号：EP3459955A1

  公开（公告）日：2019-03-27

  Biologically active compounds that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, opthamological or urological disorders are provided as well as providing methods to obtain them in pharmaceutical quality. One embodiment consists of a method to synthesize a porphyrin with a defined arrangement of meso-substituents and then converting this porphyrin system to a chlorin system by dihydroxylation or reduction, and if more than one isomer is formed separate them by chromatography either on normal or reversed phase silica. In another embodiment the substituents on the porphyrin are selected to direct the reduction or dihydroxylation to the chlorin so that a certain isomer is selectively formed. Another embodiment is to provide amphiphilic compounds with a higher membrane affinity and increased PDT-efficacy. In another embodiment a method to reductively cleave the osmate(VI)ester avoiding the use of gaseous H2S is provided. In another embodiment substituents are identified that via their steric and/or electronic influence direct the dihydroxylation or reduction with diimine so that one isomer is favored. Another embodiment consists of formulate the desired isomer into a liposomal formulation to be injected avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.

  本发明提供了可用作诊断和治疗用光敏剂的生物活性化合物，特别是用于癌症、感染和其他过度增殖性疾病的PDT、荧光诊断和关节炎、炎症性疾病、病毒或细菌感染、皮肤病、眼科或泌尿科疾病等非肿瘤适应症的PDT治疗的生物活性化合物，并提供了以药品质量获得这些化合物的方法。一个实施方案包括合成具有确定中间取代基排列的卟啉的方法，然后通过二羟基化或还原将该卟啉体系转化为氯素体系，如果形成了一个以上的异构体，则在正相或反相硅胶上通过色谱法将它们分离。在另一个实施方案中，选择卟啉上的取代基来引导还原或二羟基化为氯素，从而选择性地形成某种异构体。另一个实施方案是提供具有更高膜亲和力和更高 PDT 效能的两亲化合物。在另一个实施方案中，提供了一种避免使用气态 H2S 而还原裂解 Osmate(VI)ester 的方法。在另一个实施方案中，确定了一些取代基，这些取代基通过其立体和/或电子影响，引导二羟基化或与二亚胺的还原反应，从而使一种异构体受到青睐。另一个实施方案是将所需的异构体配制成脂质体制剂进行注射，以避免四吡咯系统的溶解性问题或药代动力学延迟等不良影响。