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    • 3. 发明申请
    • PIRENZEPINE AS AN AGENT IN CANCER TREATMENT
    • 哌仑定作为癌症治疗的代理
    • US20140271922A1
    • 2014-09-18
    • US14056028
    • 2013-10-17
    • PROTEOSYS AG
    • Andre SCHRATTENHOLZ
    • C07D487/04A61K33/24A61K45/06A61K31/551
    • C07D487/04A61K31/55A61K31/551A61K31/5513A61K31/553A61K31/554A61K33/24A61K45/06
    • The present invention generally relates to the neuroprotective activity of condensed diazepinones, e.g. condensed benzodiazepinones such as pirenzepine or compounds which are metabolized to condensed benzodiazepinones such as olanzapine. These compounds are suitable as co-medicaments for the prevention and/or treatment of drug-induced neurotoxic effects in general and neurotoxic side effects during cancer treatments with cytostatic drugs such as platinum-derivatives, e.g. cis-, carbo- and oxaliplatin, taxanes, bleomycin, cyclophosphamide and vincristine etc. Further, these compounds have an intrinisic anti-cancer activity on their own due to PARP-1 inhibition, which prevents NADH depletion in oxidative metabolism of healthy cells thus preventing the shift to anoxygenic, glycolytic metabolism present in many types of tumour cells thus eliminating this crucial metabolic advantage favouring tumour growth. These results exploit the fact of differential PARP-1 expression between many cancer cells and healthy tissues.
    • 本发明一般涉及浓缩的二氮杂酮的神经保护活性,例如 缩合苯并二氮杂酮如哌仑西平或代谢为缩合苯并二氮杂酮如奥氮平的化合物。 这些化合物适合作为用于预防和/或治疗药物诱导的神经毒性作用的共同药物,以及用细胞生长抑制药物如铂衍生物(例如,铂衍生物)治疗癌症治疗期间的神经毒副作用。 顺式,卡铂和奥沙利铂,紫杉烷,博来霉素,环磷酰胺和长春新碱等。此外,由于PARP-1抑制,这些化合物本身具有内在的抗癌活性,从而阻止健康细胞氧化代谢中的NADH消耗,从而防止 转移到存在于许多类型的肿瘤细胞中的过氧化,糖酵解代谢,从而消除了有利于肿瘤生长的这种关键的代谢优势。 这些结果利用了许多癌细胞和健康组织之间的差异PARP-1表达的事实。