CAS: 923032-37-5; (S)-N-(3,4-Difluoro-2-((2-Fluoro-4-Iodophenyl)Amino)-6-Methoxyphenyl)-1-(2,3-Dihydroxypropyl)Cyclopropane-1-Sulfonamide

该化合物是MEK1和MEK2的选择性止热抑制剂,是RAS/RAF/MEK/ERK信号传输路径的关键组成部分,在针对异常的MAPK路径激活方面表现出高度的优势,这种激活经常与各种癌症有关,尤其是那些有RAS或RAF突变的癌症有关.Refometinib 显示了有利的药用动因特性,包括口服生物利用率和持续的组织渗透.MEK1/2的特殊性将目标外影响最小化,提高了治疗精确度.临床和临床研究表明,它具有克服抗药性机制的混合疗法潜力,特别是与RAF抑制器.Refometinib的特征精良机制和临床相关性使得它成为进行肿瘤研究和定向癌症治疗发展的宝贵工具.

结构式图片

物理性质

MSDS等安全信息

欧盟法规

C&L通报

上下游产品

1-allyl-N-(3.4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)cyclopropane-1-sulfonamide N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide (S)-5-((1-iod°Cyclopropyl)methyl)-2,2,3,3,8,8,9,9-°Ctamethyl-4,7-dioxa-3,8-disiladecane (S)-3-(1-iod°Cyclopropyl)propane-1,2-diol

合成工艺路线路线简述

  • 1262760-18-8 = 923032-37-5
    反应条件:1.1 Reagents: Pyridine,Sulfolane,Hydrochloric Acid Solvents: Water; 1.5 H,Rt
    标题:Chiral Synthesis Of N-{3,4-Difluoro-2-[(2-Fluoro-4-Iodophenyl)Amino]-6-Methoxyphenyl}-1-[2,3-Dihydroxy-Propyl]Cyclopropanesulfonamides
    参考文献:World Intellectual Property Organization]

    923032-74-0 + 1262760-00-8 = 923032-37-5
    反应条件:1.1 Reagents: Pyridine,Sulfolane Catalysts: Tetrabutylammonium Bromide; 18 H,70 °C1.2 Reagents: Hydrochloric Acid,Water; 1 H
    标题:Synthesis Of Bay 86-9766/rdea-119 Via Chiral Sulfonate Intermediates
    作者:Fey,Peter; Harlow,Lisa; Beevers,Andrew
    参考文献:Ip.Com Journal 日期:2011 卷标:11]

    1262760-18-8 = 923032-37-5
    反应条件:1.1 Reagents: Hydrochloric Acid Solvents: Tetrahydrofuran,Water; Overnight,Rt
    标题:Preparation Of (R)- And (S)-N-(3,4-Difluoro-2-(2-Fluoro-4-Iodophenylamino)-6-Methoxyphenyl)-1-(2,3-Dihydroxypropyl)Cyclopropane-1-Sulfonamide And Protected Derivatives Thereof
    参考文献:World Intellectual Property Organization]

    = 923032-37-5 [标题:Reaction Conditions
    标题:Chiral Synthesis Of N-{3,4-Difluoro-2-[(2-Fluoro-4-Iodophenyl)Amino]-6-Methoxyphenyl}-1-[2,3-Dihydroxy-Propyl]Cyclopropanesulfonamides
    参考文献:United States]

    = 923032-37-5 [标题:Reaction Conditions
    标题:Preparation Of The Prodrug Compound And Their Medical Applications
    参考文献:World Intellectual Property Organization]

    = 923032-37-5 [标题:Reaction Conditions
    标题:Preparation Of N-(Arylamino)-Sulfonamide Inhibitors Of Mek
    参考文献:United States]

    923032-36-4 = 923032-37-5 + 923032-38-6 [标题:Reaction Conditions
    标题:Preparation Of N-[2-(Arylamino)Aryl] Sulfonamide Compounds As Mek Kinase Inhibitors
    参考文献:United States]

    923032-40-0 = 923032-37-5 + 923032-38-6 [标题:Reaction Conditions
    标题:Biomarkers For Determining Effective Response Of Treatments Of Hepatocellular Carcinoma Patients
    参考文献:World Intellectual Property Organization]

    923032-36-4 = 923032-37-5 + 923032-38-6 [标题:Reaction Conditions
    标题:Preparation Of N-(Arylamino)-Sulfonamide Inhibitors Of Mek
    参考文献:Brazil]

    923032-36-4 = 923032-37-5 + 923032-38-6 [标题:Reaction Conditions
    标题:Preparation Of Phenylaminophenylsulfonamides For Treatment Of Cancer And Inflammatory Disease.
    参考文献:World Intellectual Property Organization
📜Butyl 1-[(2R)-Oxiran-2-Ylmethyl]Cyclopropanesulfonate置于吡啶,环丁砜,盐酸,三氟化硼乙醚,Sodium Methylate,三溴氧磷体系中,用 甲醇,乙二醇二甲醚,水 作为反应溶剂,化学反应 24.0H,反应生成 瑞法替尼
参考文献: Chiral Synthesis Of N-{3,4-Difluoro-2-[(2-Fluoro-4-Iodophenyl)Amino]-6-Methoxyphenyl}-1-[2,3-Dihydroxy-Propyl]Cyclopropanesulfonamides[fr] Synthèse Chirale De N-{3,4-Difluoro-2-[(2-Fluoro-4-Iodophényl)Amino]-6-Méthoxyphényl}-1-[2,3-Dihydroxy-Propyl]Cyclopropanesulfonamides
标题: Chiral Synthesis Of N-{3,4-Difluoro-2-[(2-Fluoro-4-Iodophenyl)Amino]-6-Methoxyphenyl}-1-[2,3-Dihydroxy-Propyl]Cyclopropanesulfonamides[fr] Synthèse Chirale De N-{3,4-Difluoro-2-[(2-Fluoro-4-Iodophényl)Amino]-6-Méthoxyphényl}-1-[2,3-Dihydroxy-Propyl]Cyclopropanesulfonamides
摘要:该发明涉及一种新的对(S)-和(R)-对映体进行选择性的制备方法,该方法是制备n-{3,4-二氟-2-[(2-氟-4-碘苯基)氨基]-6-5-甲氧基苯基}-1-[2,3-二羟基-丙基]环丙烷磺酰胺的(S)-和(R)-对映体,以及新的中间化合物,以及利用这些新的中间化合物制备n-{3,4-二氟-2-[(2-氟-4-碘苯基)氨基]-6-甲氧基苯基}-1-[2,3-二羟基-丙基]环丙烷磺酰胺的(S)-和(R)-对映体.

海关参考信息

专利信息


专利号:US-2025289827-A1
优先权日:2022-12-02
标 题:Morphic forms of a mutant braf degrader and methods of manufacture thereof
发明人：YU ROBERT T; HE MINSHENG; SCHNADERBECK MATTHEW J; KREGER BRIDGET; POLLOCK ROY MACFARLANE; JIANG SIYI; LI MEIQI; CHEN BOLU; LU JIANNAN
权利人:C4 THERAPEUTICS INC
摘要:Advantageous isolated morphic forms of (3R)-3-[6-[2-cyano-3-[[ethyl(methyl)sulfamoyl]amino]-6-fluorophenoxy]-4-oxoquinazolin-3-yl]-8-[2-[1-[3-(2,4-dioxo-1,3-diazinan-1-yl)-5-fluoro-1-methylindazol-6-yl]-4-hydroxypiperidin-4-yl]acetyl]-1-oxa-8-azaspiro[4.5]decane (Compound 1), which is a mutant BRAF degrader, and methods to prepare Compound 1 morphic forms for therapeutic applications are provided in the invention. The invention also provides improved methods for the synthesis of Compound 1, new pharmaceutical compositions comprising Compound 1, and new uses of Compound 1.

专利号:US-9328066-B2
优先权日:2011-05-27
标 题 :Chiral synthesis of N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamides
发明人：FEY PETER; MAYER AGATHE CHRISTINE
权利人:FEY PETER; MAYER AGATHE CHRISTINE; BAYER IP GMBH
摘要:The present invention relates to a novel enantioselective method of preparing (S)- and (R)-enantiomers of N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-5 methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamide, to novel intermediate compounds, and to the use of said novel intermediate compounds for the preparation of said (S)- and (R)-enantiomers of N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamide.

专利号:CA-2837162-A1
优先权日:2011-05-27
标 题:Chiral synthesis of n-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamides

专利号:MY-186875-A
优先权日:2011-05-27
标 题:Chiral synthesis of n-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamides

专利号:EP-2714652-A1
优先权日:2011-05-27
标题:Chiral synthesis of n-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamides

专利号:US-2014155637-A1
优先权日:2011-05-27
标题 :Chiral synthesis of n--1-[2,3-dihydroxy-propyl]cyclopropanesulfonamides

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主要参考文献


1: Wylie-Sears J, Levine RA, Bischoff J. Losartan inhibits endothelial-to-mesenchymal transformation in mitral valve endothelial cells by blocking transforming growth factor-β-induced phosphorylation of ERK. Biochem Biophys Res Commun. 2014 Mar 12. pii: S0006-291X(14)00445-8. doi: 10.1016/j.bbrc.2014.03.014. [Epub ahead of print] doi: 10.1158/1078-0432.CCR-12-3529. Epub 2013 Feb 22. doi: 10.3109/1354750X.2012.689133. Epub 2012 May 23. doi: 10.1371/journal.pone.0031729. Epub 2012 Feb 16.
5: Holm TM, Habashi JP, Doyle JJ, Bedja D, Chen Y, van Erp C, Lindsay ME, Kim D, Schoenhoff F, Cohn RD, Loeys BL, Thomas CJ, Patnaik S, Marugan JJ, Judge DP, Dietz HC. Noncanonical TGFβ signaling contributes to aortic aneurysm progression in Marfan syndrome mice. Science. 2011 Apr 15;332(6027):358-61. doi: 10.1126/science.1192149.
6: Diep CH, Munoz RM, Choudhary A, Von Hoff DD, Han H. Synergistic effect between erlotinib and MEK inhibitors in KRAS wild-type human pancreatic cancer cells. Clin Cancer Res. 2011 May 1;17(9):2744-56. doi: 10.1158/1078-0432.CCR-10-2214. Epub 2011 Mar 8.

合成参考文献


参考文献:10.1016/s1470-2045(18)30505-9
摘要:Das M. Refametinib in RAS-mutated hepatocellular cancer. Lancet Oncol. 2018 Aug;19(8):e389. doi: 10.1016/s1470-2045(18)30505-9.
参考文献:10.1124/mol.119.115964
摘要:Lee TD, Lee OW, Brimacombe KR, Chen L, Guha R, Lusvarghi S, Tebase BG, Klumpp-Thomas C, Robey RW, Ambudkar SV, Shen M, Gottesman MM, Hall MD. A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Molecular Pharmacology. 2019 Nov;96(5):629–40. doi: 10.1124/mol.119.115964.
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