抗癌药物奥拉帕尼重要中间化合物的合成研究

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摘要：奥拉帕尼化学名是1-（环丙甲酞基)4-[5-[(3,4-二氢4氧代-1-酞嗪基)甲基]-2氟苯甲酰哌嗪。奥拉帕尼为一种全新的口服聚腺普二磷酸酷核糖聚合酶抑制剂，奥拉帕尼是利用DNA修复途径中的缺陷，优先去杀死癌细胞。同时又可以增强放疗和烷化剂以及铂类药物的化疗疗效。奥拉帕尼的研究目前正处于临床的Ⅱ期，它是主要被用在治疗乳腺癌基因一号或二号的基因突变癌中。42337

癌症亦被称为恶性肿瘤，是一类异常细胞增殖和快速和特征转移的疾病，其已经对人体健康造成严重威胁。目前主要有三种途径用于癌症治疗：放射治疗，手术和化疗。在最近几年，基于对癌症的出其认识指出，癌症的治疗涉及了用于抑制细胞内的转导的蛋白激酶靶向药物治疗的方法产生的信号。据国际癌症研究中心的统计，每年约有20万卵巢癌病例中，占了女性的恶性肿瘤近13.3％。其中，英国每年有卵巢癌7000个案，有死亡的4200例妇女患卵巢癌；每年美国有22500例而且死亡的居然占到14000例。卵巢癌是其中一个女性生殖器官非常常见的恶性肿瘤，它的死亡率与近年居高不下，时至今日它的死亡率居妇科恶性肿瘤首位，且发病率逐年上升。

本实验用有机合成的方法合成奥拉帕尼，首先通过对奥拉帕尼的结构进行解析，运用逆合成分析法将奥拉帕尼的合成分成四步，有机合成法合成奥拉帕尼产率优异且反应条件易于施行，是较为理想的合成方法。

毕业论文关键词：奥拉帕尼；癌；遗传性；卵巢癌；有机合成

Synthesis of anticancer drugs Olaparib important intermediate compound

Abstract:Also known as malignant cancer, is - class to abnormal cell proliferation and metastasis of rapid disease characterized, it has been a serious threat to human health. Currently there are three main ways cancer treatment: radiation therapy, surgery and chemotherapy. In recent years, the foundation points for cancer awareness, cancer treatment involves generating a signal for inhibiting the intracellular transduction protein kinase targeted drug therapy approach. According to the International Cancer Research Center statistics, each year about 200,000 ovarian cancer cases, women accounted for nearly 13.3% of malignant tumors. Among them, the UK Every year, 7,000 cases of women suffering from ovarian cancer, 4200 cases of death； and the United States each year there are 22,500 cases, 14,000 cases of death. Ovarian cancer is a common malignancy of the female genital organs - the mortality rate of ovarian cancer is one of common malignant tumors of female genital mutilation, the mortality rate ranks first in gynecological malignancies, and the incidence rate increased year by year.

Olaparib chemical name 1- (cyclopropylmethyl phthalidyl A) 4- [5 - [(3,4-dihydro-phthalazin-4-oxo-1-yl) methyl] -2-fluorobenzoyl piperidine triazine. Olaparib is a new oral poly glandular Cape cool diphosphate ribose polymerase (PARP) inhibitor, which utilizes DNA repair pathway defects, priority to kill cancer cells. While enhancing the efficacy of such radiation and alkylating agents and platinum-based chemotherapy. Olaparib is currently in clinical phase Ⅱ, mainly for the treatment of breast cancer gene mutations One or II cancer (mainly in breast cancer, ovarian cancer, etc.).

The experimental method for the synthesis of organic synthesis Olaparib, first by Ola parib structure analysis, using inverse synthetic analysis method Qlaparib synthetic pided into four steps, the synthesis of organic synthesis production Olaparib excellent rate and the reaction conditions easy implementation, is an ideal synthesis.

Keywords ： olaparib； cancer, ovarian cancer ； heritable；Organic Synthesis

1 绪论

肿瘤，是由各种因素致瘤的影响人体的引起细胞质的延迟改变，包括在肿瘤原癌基因的扩增、突变还有或者是损失抑癌基因，并且使基因表达发生变化，异常的细胞增殖而结果形成新的生物。肿瘤细胞具有独立或相对独立的生长能力，所以即使致癌物质停止它的作用后肿瘤后仍然可以持续增长。根据肿瘤对身体的损害程度及其生长特性可以将肿瘤分为三类：良性的，恶性的、良性和恶性之间的交界肿瘤。