The present invention provides methods to obtain 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, ophthalmological or urological disorders. An embodiment of the present invention consists of a method to synthesize diketo-chlorins as precursors. In yet another embodiment these precursors are converted to β-functionalized hydroxy- and dihydroxy-chlorins. Another embodiment is to provide amphiphilic compounds with a higher membrane affinity and increased PDT-efficacy. Another embodiment consists of the formulation of the desired isomer into a liposomal formulation to be injected avoiding undesirable effects like precipitation at the injection site or delayed pharmacokinetics of the tetrapyrrole systems.
本发明提供了一种获得
生物活性化合物的方法,这些化合物可以用作诊断和治疗应用的光敏剂,特别是用于癌症、感染和其他过度增殖性疾病的光动力疗法(PDT),荧光诊断和非肿瘤指示物(如关节炎、炎症性疾病、病毒或细菌感染、皮肤病、眼科疾病或泌尿系统疾病)的PDT治疗。本发明的一种实施例包括合成二酮-叶绿素作为前体的方法。在另一种实施例中,这些前体被转化为β-官能化的羟基和二羟基-叶绿素。另一种实施例是提供具有更高膜亲和力和增加PDT效果的两性化合物。另一种实施例包括将所需的异构体制成脂质体制剂以注射,避免不良影响,如在注射部位沉淀或四
吡咯系统的延迟药代动力学。