Tafamidis中间体I的合成研究开题报告

1. 研究目的与意义（文献综述包含参考文献）

文 献 综 述1、tafamidis的简介attr-cm用于治疗成人野生型或遗传型转甲状腺素蛋白淀粉样变性心肌病（attr-cm），以减少心血管死亡及心血管相关的住院治疗，是一种用于治疗attr-cm罕见病的药品。

vyndaqel，tafamidis meglumine是一种转甲状腺素蛋白稳定剂，用于治疗野生型或遗传性转甲状腺素介导的淀粉样变性的心肌病。

fda已经接受其用于治疗转甲状腺素蛋白淀粉样变性心肌病（attr-cm）在研药物tafamidis的新药申请。

2. 研究的基本内容、问题解决措施及方案

毕 业 设 计（论 文）开 题 报 告２．本课题要研究或解决的问题和拟采用的研究手段（途径）：研究主题：1、通过文献综述了解tafamidis的研究背景与进展；2、完成tafamidis中间体i的合成。

研究途径： 将 4-氨基-3-羟基苯甲酸氯苯甲酰氯酰化，所得产物对甲苯磺酸合物处理，成的残余物(三甲基甲硅烷基)重氮甲烷酯化，环化，最后解产tafamidis。

tafamidis 中间体Ⅰ的合成1、1,3-苯并噁唑-6-羧酸甲酯为起始原料，与氯化亚砜、甲醇进行缩合反应2、碱性条件下，将化合物在有机溶剂中进行缩合反应，得到中间体Ⅰ参考文献1.stern lily k.,kittleson michelle m.. updates in cardiac amyloidosis diagnosis and treatment[j]. current oncology reports,2021,23(4):12.huh yeamin,riley steve,harnisch lutz,nicholas timothy. population pharmacokinetic modelling and simulation of tafamidis in healthy subjects and patients with transthyretin amyloidosis.[j]. british journal of clinical pharmacology,2021,87(9):3.psotka mitchell a.. tafamidis should be accessible for all patients with transthyretin amyloid cardiomyopathy[j]. jacc: heart failure,2021,9(2):4.lamb yvette n.. tafamidis: a review in transthyretin amyloid cardiomyopathy[j]. american journal of cardiovascular drugs,2021,21(1):5.rapezzi claudio,elliott perry,damy thibaud,nativi nicolau jose,berk john l.,velazquez eric j.,boman kurt,gundapaneni balarama,patterson terrell a.,schwartz jeffrey h.,sultan marla b.,maurer mathew s.. efficacy of tafamidis in patients with hereditary and wild-type transthyretin amyloid cardiomyopathy: further analyses from attr-act[j]. jacc: heart failure,2020(prepublish):6.田庄,张抒扬.氯苯唑酸治疗转甲状腺素心脏淀粉样变[j].中华心血管病杂志,2021,49(04):314-317.7.田野,赵燕芳.tafamidis meglumine(vyndaqel)[j].中国药物化学杂志,2020,30(02):127.doi:10.14142/j.cnki.cn21-1313/r.2020.02.010.8.孟佳欣,赵冬梅.tafamidis治疗转甲状腺素淀粉样变性的研究进展[j].临床药物治疗杂志,2019,17(11):1-5.9.tafamidis, a noninvasive therapy for delaying transthyretin familial amyloid polyneuropathy: systematic review and meta-analysis[j]. journal of clinical neurology (seoul, korea),2019,15(1):10. efficacy of tafamidis in transthyretin amyloid cardiomyopathy in the attr-act trial[j]. heart lung,2019,48(5):11.ferrer-nadal asuncion,ripoll tomas,uson mercedes,figuerola antoni,andreu hernan,losada ines,gonzalez juan,cisneros-barroso eugenia,buades juan. significant reduction in proteinuria after treatment with tafamidis.[j]. amyloid : the international journal of experimental and clinical investigation : the official journal of the international society of amyloidosis,2019,26(sup1):12.benjamin li,jose alvir,michelle stewart. extrapolation of data from the tafamidis in transthyretin cardiomyopathy clinical trial (attr-act) further highlights the survival benefit of tafamidis in transthyretin amyloid cardiomyopathy[j]. journal of cardiac failure,2019,25(8):13.mazen hanna,michelle stewart,balarama gundapaneni,terrell a. patterson,jeffrey h. schwartz,marla s. sultan,mathew s. maurer. tafamidis reduced the decline in health-related quality of life in the tafamidis in transthyretin cardiomyopathy clinical trial (attr-act)[j]. journal of cardiac failure,2019,25(8):14.lamb yvette n,deeks emma d. tafamidis: a review in transthyretin amyloidosis with polyneuropathy.[j]. drugs,2019,79(8):15.ikeda shu-ichi,hineno akiyo,ichikawa tohru,makino mutsuki. tafamidis dramatically improved severe proteinuria in a patient with ttr v30m hereditary attr amyloidosis.[j]. amyloid : the international journal of experimental and clinical investigation : the official journal of the international society of amyloidosis,2019,26(2):16.ferrer-nadal asuncion,ripoll tomas,mercedes uson,figuerola antoni,descals cristina,montala carles,andreu hernan,cisneros-barroso eugenia,gonzalez juan,losada ines,buades juan. sp198significant reduction in proteinuria after treatment with tafamidis[j]. nephrology dialysis transplantation,2019,34(supplement1):17.m. grogan,r. witteles,s.j. shah,j.h. schwartz,b. gundapaneni,t.a. patterson,m.b. sultan,m.s. maurer. efficacy of tafamidis in patients with hereditary or wild-type transthyretin amyloid cardiomyopathy: further results from the attr-act trial[j]. journal of heart and lung transplantation,2019,38(4):18.fang‐ching lee,ryuji sakakibara,fuyuki tateno,yosuke aiba,masahiko kishi,hiroyoshi suzuki,ayami shimizu,osamu takahashi,nobuo takada. tafamidis improves bladder function in hereditary attr amyloidosis[j]. neurology and clinical neuroscience,2019,7(2):19. fda oks regulatory submissions for review of tafamidis to treat transthyretin amyloidcardiomyopathy[j]. manufacturing close - up,2019:20.le bras alexandra. tafamidis: a new treatment for attr cardiomyopathy.[j]. nature reviews. cardiology,2018,15(11):