CAS: 441798-33-0; N-(5-(4-Bromophenyl)-6-(2-((5-Bromo-2-Pyrimidinyl)Oxy)Ethoxy)-4-Pyrimidinyl)-N'-Propylsulfamide

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N-[5-(4-溴苯基)-6-(2-羟基乙氧基)-4-嘧啶基]-N'-丙基氨基磺酰胺 N-[5-(4-Bromophenyl)-6-[2-Hydroxyethoxy]-4-Pyrimidinyl]-N-Propylsulfamide 1393813-43-8
N-[5-(4-溴苯基)-6-氯-4-嘧啶基]-N'-丙基氨基磺酰胺 N-5-(4-Bromophenyl)-6-Chloro-4-Pyrimidinyl-N'-Propylsulfamide 1393813-42-7

4-溴苯乙酸甲酯置于potassium Tert-Butylate,Sodium,Sodium Hydride,三氯氧磷体系中,用 四氢呋喃,甲醇,乙二醇二甲醚,二甲基亚砜,N,N-二甲基苯胺,Mineral Oil 作为反应溶剂,化学反应 173.42H,反应生成 马西替坦
参考文献:的发现ñ-[5-(4-溴苯基)-6-[2-[(5-溴-2-嘧啶基)氧基]乙氧基]-4-嘧啶基]-ñ '-Propylsulfamide(美西特田),一种口服活性,强效双重内皮素受体拮抗剂
标题:的发现ñ-[5-(4-溴苯基)-6-[2-[(5-溴-2-嘧啶基)氧基]乙氧基]-4-嘧啶基]-ñ '-Propylsulfamide(美西特田),一种口服活性,强效双重内皮素受体拮抗剂
摘要:从波生坦(1)的结构开始,我们着手于一项药物化学程序,旨在鉴定具有高口服功效的新型有效的双重内皮素受体拮抗剂.这导致发现了一系列新的烷基磺酰胺取代的嘧啶.其中,化合物17(macitentan,Act-064992)引起了人们的特别关注,因为它是对et B受体具有显着亲和力的et A的有效抑制剂,并且在高血压dahl盐敏感性大鼠中显示出优异的药代动力学特性和高体内功效.化合物17成功完成了一项肺动脉高压的长期iii期临床试验.
DOI:10.1021/jm3009103

专利信息

专利号:WO-2025102245-A1
优先权日:2023-11-14
标题:Synthesis method for dual endothelin receptor antagonist aprocitentan
发明人：XU XIANGUANG; WANG ZHEN; ZHU GUORONG; TU YONGJUN
权利人:ZHEJIANG TIANYU PHARMACEUTICAL CO LTD
摘要:Provided in the present invention is a synthesis method for aprocitentan, comprising the following steps: 1) a compound of formula X and a sulfonylation reagent compound of formula XI undergoing a sulfonylation reaction to prepare a compound of formula XII; and 2) removing an R protective group on the pyrimidine sulfonamide compound of formula XII obtained in the previous step, so as to obtain aprocitentan. The synthesis method of the present invention overcomes the problem in the prior art that preparing macitentan by means of condensation of chloropyrimidine and sulfonamide needs to use an excessive amount of a strong base and involves a relatively low conversion efficiency, relatively many side products and other defects. The synthesis method does not need using a fluorine reagent for fluorination, involves economical steps, is environmentally-friendly, and has a relatively low comprehensive production cost. Compared with existing methods for preparing aprocitentan, the method of the present invention has characteristics of easily available raw materials, being environmentally-friendly and economical, and the like, thereby facilitating the industrial production of aprocitentan.

专利号:US-11667610-B2
优先权日:2016-09-28
标题:Method for preparing Macitentan and intermediate compound thereof
发明人：JIA QIANG; MA CHI; YANG ZHENGWEI; YANG JINJIN
权利人:SEASONS BIOTECHNOLOGY TAIZHOU CO LTD
摘要:The present invention relates to technical field of chemical synthesis of drugs, and provides a preparation method of Macitentan and intermediate compound thereof. Adding THF solution containing compound II and 5-bromo-2-chloropyrimidine slowly into THF solution containing base to react, or adding THF solution containing compound II and THF solution containing 5-bromo-2-chloropyrimidine slowly at the same time into THF solution containing base to react and obtain Macitentan (shown as compound I), wherein the base is selected from sodium hydride, potassium hydride, lithium hydride or lithium bis(trimethylsilyl)amide. The selectivity of the preparation method is very good, which is suitable for industrial production. The obtained product Macitentan has good quality and high yield. And the product compound II also has good quality and high yield, its HPLC purity is up to 99.0%, the content of impurity A is less than 0.20%, the content of impurity B is less than 0.25%.

专利号:US-10906888-B2
优先权日:2016-07-14
标 题:Pyrimidine carboxamides as inhibitors of Vanin-1 enzyme
发明人：CASIMIRO-GARCIA AGUSTIN; STROHBACH JOSEPH WALTER; HEPWORTH DAVID; LOVERING FRANK ELDRIDGE; CHOI CHULHO; ALLAIS CHRISTOPHE PHILIPPE; WRIGHT STEPHEN WAYNE
权利人:PFIZER
摘要:Compounds, pharmaceutically acceptable salts thereof, are disclosed wherein the compounds have the structure of (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

专利号:US-10308615-B2
优先权日:2015-05-29
标 题:Heterocyclic compounds as inhibitors of Vanin-1 enzyme
发明人：CASIMIRO-GARCIA AGUSTIN; CONDON JEFFREY SCOTT; FLICK ANDREW CHRISTOPHER; GOPALSAMY ARIAMALA; KIRINCICH STEVEN J; MATHIAS JOHN PAUL; STROBACH JOSEPH WALTER; XIANG JASON SHAOYUN; XING LI HUANG; WANG XIAOLUN
权利人:PFIZER
摘要:Compounds, pharmaceutically acceptable salts thereof, are disclosed wherein the compounds have the structure of n nas defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

专利号:US-2018230127-A1
优先权日:2015-08-13
标题 :Bicyclic-Fused Heteroaryl Or Aryl Compounds
发明人：ANDERSON DAVID RANDOLPH; CURRAN KEVIN JOSEPH; GAVRIN LORI KRIM; GOLDBERG JOEL ADAM; LEE ARTHUR; LOWE MICHAEL DENNIS; PATNY AKSHAY; PIERCE BETSY SUSAN; SAIAH EDDINE; TRZUPEK JOHN DAVID
权利人:PFIZER
摘要:Compounds, tautomers and pharmaceutically acceptable salts of the compounds of Formula (Ia) are disclosed which are inhibitors of Interleukin-1 receptor associated kinase (IRAK4). Methods of treatment, methods of synthesis, and intermediates are also disclosed as defined in the specification.

专利号:US-10316018-B2
优先权日:2015-08-27
标题 :Bicyclic-fused heteroaryl or aryl compounds as IRAK4 modulators
发明人：LEE KATHERINE LIN; ALLAIS CHRISTOPHE PHILIPPE; DEHNHARDT CHRISTOPH MARTIN; GAVRIN LORI KRIM; HAN SEUNGIL; HEPWORTH DAVID; LEE ARTHUR; LOVERING FRANK ELDRIDGE; MATHIAS JOHN PAUL; OWEN DAFYDD RHYS; PAPAIOANNOU NIKOLAOS; SAIAH EDDINE; STROHBACH JOSEPH WALTER; TRZUPEK JOHN DAVID; WRIGHT STEPHEN WAYNE; ZAPF CHRISTOPH WOLFGANG
权利人:PFIZER
摘要:Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula Ia, n nas defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.