SYNTHESIS AND ANTITUMOR EVALUATION OF CC1065 ANALOGS

CC-1065类似物是发现的最有效的抗癌药物之一 并且具有独特的抗肿瘤作用机制。 CC-1065的衍生物 缺乏其延迟毒性，具有显著的抗肿瘤活性， 临床试验 然而，对人类骨髓的抑制破坏了 其临床效果。两种新的外消旋CC-1065类似物YW-200和 YW-213具有显著的体内抗肿瘤活性， 骨髓抑制，其他CC-1065类似物的剂量限制性毒性。 我们拟合成和评价天然对映体（+）-YW-200， （+）-YW-201，YW-213的前体。 （+）-YW-200和（+）-YW-201将具有 提高了抗肿瘤效果，副作用少。 总目标 第二阶段是临床前开发，最终目标是提交 一个IND。 拟议的商业应用： 一类新型抗癌药物具有巨大且不断增长的市场。

CC-1065 analogs are among the most potent anti-cancer drugs discovered and have unique mechanisms of antitumor action. Derivatives of CC-1065 lacking its delayed toxicity have significant antitumor activity in clinical trials. However, suppression on human bone marrow undermines their clinical effectiveness. Two new racemic CC-1065 analogs, YW-200 and YW-213 show remarkable antitumor activity in vivo without causing myelosuppression, the dose-limiting toxicity for other CC-1065 analogs. We propose to synthesize and evaluate natural enantiomeric (+)-YW-200 and (+)-YW-201, a precursor to YW-213. (+)-YW-200 and (+)-YW-201 will have improved antitumor efficacy with fewer side-effects. The overall goal of phase II is pre-clinical development with the ultimate goal of filing an IND. PROPOSED COMMERCIAL APPLICATIONS: A novel class of anti-cancer drugs has a substantial and growing market.