CAS: 123663-49-0; N-(7-(Methylsulfonamido)-4-Oxo-6-Phenoxy-4H-Chromen-3-yl)Formamide

该化合物是一种合成小分子,被归类为免疫分子,主要用于治疗风湿性关节炎,其化学结构具有有助于其药理活动的功能组的独特组合.Iguratimod通过阻止生产亲食性细胞细胞素和调制免疫反应,帮助减少与自免疫条件有关的炎症和联合损伤.该物质以相对有利的安全性特征而著称,与传统的疾病改良抗血病药物(DARDs)相比,它相对有利.就溶液而言,Iguratimod一般在有机溶剂中溶解,但水中的溶性有限,这可能影响其生物利用率.该化合物通常通过口授方式管理,并在肝脏中进行代谢,其药理基因受各种因素影响,包括剂量和个人病人特征.

结构式图片

欧盟法规

ECHA物质C&L通报

上下游产品

N,N-dimethyl-formamide dimethyl acetalN,N-dimethyl-formamide dimethyl acetal α-formamido-2'-hydroxy-4'-methanesulfonamido-5'-phenoxyacetophenone formyl acetic anhydride N-(3-amino-4-oxo-6-phenoxy-4H-1-benzopyran-7-yl)methanesulfonamideN-[3-(formylamino)-4-oxo-6-phenoxy-4H-chromen-7-yl]methanesulfonamide monohydrate

合成工艺路线路线简述

    艾拉莫德杂质1 以75的收率获得艾拉莫德
    参考文献:3-(甲酰胺)-7-(甲磺酰胺)-6-(苯氧基)-4H-1-(苯并吡喃)-4-酮的制备方法
    标题:3-(甲酰胺)-7-(甲磺酰胺)-6-(苯氧基)-4H-1-(苯并吡喃)-4-酮的制备方法
    摘要:本发明公开了一种抗炎药3-(甲酰胺)-7-(甲磺酰胺)6-(苯氧基)-4H-1-苯并吡喃-4-酮的制备方法.它以3-苯氧基-4-甲磺酰胺-6-甲氧基苯乙酮(化合物1)为原料,经脱甲基制得化合物2,环合生成化合物3,经催化氢化制成为化合物4,经溴代生成化合物5,经插烯胺化制得化合物6,经甲酰化生成3-(甲酰胺)-7-(甲磺酰胺)-6-(苯氧基)-4H-1-苯并吡喃-4-酮(T-614).本发明的方法可用如上述反应式表示.

    海关参考信息

    专利信息


    专利号:US-11993606-B2
    优先权日:2015-10-16
    标题:Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
    发明人:MOHAMED MOHAMED-ESLAM F; OTHMAN AHMED A; PANGAN AILEEN L; SONG IN-HO; KLÜNDER BEN; VOSS JEFFREY W; PADLEY ROBERT J; CAMP HEIDI S
    权利人:ABBVIE INC
    摘要:The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis and various spondyloarthritic conditions, including types of axial spondyloarthritis (axSpA)), kits, methods of synthesis, and products-by-process. In various aspects, provided are methods for treating active non-radiographic axSpA (nr-axSpA) and methods for treating active ankylosing spondylitis (AS).

    专利号:US-11512092-B2
    优先权日:2015-10-16
    标题 :Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
    发明人:ALLIAN AYMAN; JAYANTH JAYANTHY; MOHAMED MOHAMED-ESLAM F; MULHERN MATHEW; NORDSTROM FREDRIK LARS; OTHMAN AHMED A; ROZEMA MICHAEL J; BHAGAVATULA LAKSHMI; MARROUM PATRICK J; MAYER PETER T; SHEIKH AHMAD Y; BORCHARDT THOMAS B; KLÜNDER BEN
    权利人:ABBVIE INC
    摘要:The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis and various spondyloarthritic conditions, including types of axial spondyloarthritis (axSpA)), kits, methods of synthesis, and products-by-process. In various aspects, provided are methods for treating active non-radiographic axSpA (nr-axSpA) and methods for treating active ankylosing spondylitis (AS).

    专利号:US-11524964-B2
    优先权日:2015-10-16
    标题:Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
    发明人:MOHAMED MOHAMED-ESLAM F; OTHMAN AHMED A; KLÜNDER BEN; PANGAN AILEEN L; SONG IN-HO
    权利人:ABBVIE INC
    摘要:The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis and various spondyloarthritic conditions, including types of axial spondyloarthritis (axSpA)), kits, methods of synthesis, and products-by-process. In various aspects, provided are methods for treating active non-radiographic axSpA (nr-axSpA) and methods for treating active ankylosing spondylitis (AS).

    专利号:US-11993605-B2
    优先权日:2015-10-16
    标 题:Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
    发明人:MOHAMED MOHAMED-ESLAM F; OTHMAN AHMED A; KLÜNDER BEN; PANGAN AILEEN L; ANDERSON JACLYN KAY; VOSS JEFFREY W; PADLEY ROBERT J; CAMP HEIDI S
    权利人:ABBVIE INC
    摘要:The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis), kits, methods of synthesis, and products-by-process.

    专利号:CN-116891450-A
    优先权日:2022-12-29
    标 题:Synthesis method of Iguratimod
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    主要参考文献


    1: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Oct;30(8):643-72. Epub 2007 Feb 20. Epub 2007 Feb 20. Chinese.

    合成参考文献


    参考文献:10.1007/s00277-018-3327-4
    摘要:Takanashi S, Nakazato T, Aisa Y, Ito C, Arakaki H, Osada Y, Hirano M, Mori T. The prognostic value of positron emission tomography/computed tomography in rheumatoid arthritis patients with methotrexate-associated lymphoproliferative disorders. Ann Hematol. 2018 Sep;97(9):1611–8. doi: 10.1007/s00277-018-3327-4.
    参考文献:10.1186/s13075-018-1548-5
    摘要:Chen YL, Lin JZ, Mo YQ, Ma JD, Li QH, Wang XY, Yang ZH, Yan T, Zheng DH, Dai L. Deleterious role of hepatitis B virus infection in therapeutic response among patients with rheumatoid arthritis in a clinical practice setting: a case-control study. Arthritis Res Ther. 2018 May 02;20(1):81.
    参考文献:10.1111/1756-185x.13633
    摘要:Zhang P, Gong Y, Liu Z, Liu Y, Lin W, Li J, Wang M, Liu X, Fei Y, Chen H, Peng L, Li J, Zhou J, Shi Q, Zhang X, Shen M, Zeng X, Zhang F, Li Y, Zhao Y, Zhang W. Efficacy and safety of iguratimod plus corticosteroid as bridge therapy in treating mild IgG4‐related diseases: A prospective clinical trial. Int J of Rheum Dis. 2019 Jun 27;22(8):1479–88. doi: 10.1111/1756-185x.13633.
    参考文献:10.1371/journal.pone.0253513
    摘要:Shibata K, Yoshimura A, Ikeuchi S, Ishii M. Effectiveness of drug safety measures for reducing the incidence of adverse drug reactions: Post-hoc analysis of data from all-case surveillance of iguratimod using generalized estimating equations. PLoS ONE. 2021 Jul 30;16(7):e0253513. doi: 10.1371/journal.pone.0253513.
    参考文献:10.1186/s12931-022-01978-y
    摘要:Hozumi H, Kono M, Hasegawa H, Kato S, Inoue Y, Suzuki Y, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Inui N, Nakamura Y, Yokomura K, Nakamura H, Suda T. Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: mortality and its prediction model. Respiratory Research. 2022 Mar 11;23(1):57. doi: 10.1186/s12931-022-01978-y.
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