达拉非尼合成路线图解Graphical synthetic routes of dabrafenib
张茂风,张玉梁,吴锡山,钱岳杭,张立光
摘要(Abstract)：
<正>达拉非尼(dabrafenib,1)商品名为Tafinlar，中文化学名称为N-{3-[5-(2-氨基-4-嘧啶基)-2-(叔丁基)-4-噻唑基]-2-氟苯基}-2,6-二氟苯磺酰胺，英文化学名称为N-{3-[5-(2-aminopyrimidin-4-yl)-2-(tert-butyl) thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide，分子式为C_(23)H_(20)F_3N_5O_2S_2，分子量为519.56,CAS登记号为1195765-45-7。达拉非尼最早由葛兰素史克公司开发，当前为诺华公司所有。达拉非尼是一款BRAF(B rapidly accelerated fibrosarcoma)酪氨酸激酶抑制剂，其对BRAF V600E突变型激酶抑制活性的IC_(50)值为0.7 nmol·L~(-1[1])，此外对BRAF V600K和BRAF V600D等突变型激酶也具有较强的抑制活性~([2])。
关键词(KeyWords)：
基金项目(Foundation): 江苏高校‘青蓝工程’项目(苏教师函﹝2023﹞27号);; 苏州市科技计划项目(基础研究计划-医学应用基础研究)(SKY2023135);; 苏州卫生职业技术学院科技创新团队项目(SZWZYTD202204)
作者(Author): 张茂风,张玉梁,吴锡山,钱岳杭,张立光
DOI: 10.14142/j.cnki.cn21-1313/r.2023.12.009
参考文献(References)：
- [1] RHEAULT T R,STELLWAGEN J C,ADJABENG G M,et al.Discovery of dabrafenib:a selective inhibitor of raf kinases with antitumor activity against B-Raf-driven tumors[J].ACS Med Chem Lett,2013,4(3):358-362.
- [2] GENTILCORE G,MADONNA G,MOZZILLO N,et al.Effect of dabrafenib on melanoma cell lines harbouring the BRAFV600D/R mutations[J].BMC Cancer,2013,13(1):17.
- [3] MENZIES A M,LONG G V,MURALI R.Dabrafenib and its potential for the treatment of metasta-tic melanoma[J].Drug Des Devel Ther,2012,6:391-405.
- [4] US FDA.FDA grants regular approval to dabrafenib and trametinib combination for metastatic NSCLC with BRAF V600E mutation[EB/OL].[2023-07-08].https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-appro-val-dabrafenib-and-trametinib-combination-metastatic-nsclc-braf-v600e.
- [5] AULIAC J B,BAYLE S,DO P,et al.Efficacy of dabrafenib plus trametinib combination in patients with BRAF V600E-mutant NSCLC in real-world setting:GFPC 01-2019[J].Cancers,2020,12(12):3608.
- [6] 中国临床肿瘤学会.非小细胞肺癌诊疗指南[M].北京：人民卫生出版社，2021:122-124.Chinese Society of Clinical Oncology.Guidelines of Chinese Society of Clinical Oncology(CSCO) non-small cell lung cancer[M].Beijing:People′s Medical Publishing House,2021:122-124.
- [7] US FDA.FDA approves dabrafenib plus trametinib for anaplastic thyroid cancer with BRAF V600E mutation[EB/OL].[2023-07-08].https://www.fda.gov/drugs/resources-information-approved-dru gs/fda-approves-dabrafenib-plus-trametinib-anaplastic-thyroid-cancer-braf-v600e-mutation.
- [8] US FDA.FDA grants accelerated approval to dabrafenib in combination with trametinib for unresec-table or metastatic solid tumors with BRAF V600E mutation[EB/OL].[2023-07-08].https://www.fda.gov/drugs/resources-information-ap-proved-drugs/fda-grants-accelerated-approval-dab-rafenib-combination-trametinib-unresectable-or-metastatic-solid.
- [9] US FDA.FDA approves dabrafenib with trametinib for pediatric patients with low-grade glioma with a BRAF V600E mutation[EB/OL].[2023-07-08].https://www.fda.gov/drugs/resources-infor-mation-approved-drugs/fda-approves-dabrafenib-tra-metinib-pediatric-patients-low-grade-glioma-braf-v600e-mutation.
- [10] KIM T,MCCARVER S J,LEE C,et al.Sulfonami-dation of aryl and heteroaryl halides through photosensitized nickel catalysis[J].Angew Chem Int Edit,2018,57(13):3488-3492.
- [11] LI Q,XU L,MA D.Cu-catalyzed coupling reactions of sulfonamides with(hetero) aryl chlorides/bromides[J].Angew Chem Int Edit,2022,61(43):e202210483.
- [12] 任伟.黑色素瘤新药达拉菲尼的制备方法：中国，201711449350.6[P].2017-12-27.REN W.Method for preparing new drug dabrafenib for melanoma:CN,201711449350.6[P].2017-12-27.
- [13] DUMBLE M,KUMAR R,LAQUERRE S,et al.Combination:WO,2011047238[P].2011-04-21.
- [14] HOOS A,GRESHOCK J.Combination:WO,2014066606[P].2014-05-01.
- [15] HAM W S,CHOI H,ZHANG J,et al.C2-selective,functional-group-divergent amination of pyrimidines by enthalpy-controlled nucleophilic functionalization[J].J Am Chem Soc,2022,144(7):2885-2892.
- [16] HOOS A.Combinations of an anti-PD-L1 antibody and a MEK inhibitor and/or a BRAF inhibitor:WO,2014195852[P].2014-12-11.
- [17] CAPONIGRO G,HORN-SPIROHN T,LEHAR J.Pharmaceutical combination comprising the PI3K inhibitor alpelisib and the B-Raf inhibitor dabrafenib;the use of such combination in the treatment or prevention of cancer:WO,2017037573[P].2017-03-09.
- [18] PRUDENT R,PAUBLANT F.Lim kinase inhibitors,pharmaceutical composition and method of use in limk-mediated diseases:WO,2018055097[P].2018-03-29.
- [19] DAI X,WANG Y,JIANG Y,et al.C-terminal SRC kinase inhibitors:WO,2020125615[P].2020-06-25.