6-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-[(S)-(tetrahydrofuran-2-yl)methoxy]quinazoline | 439081-59-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-Amino-4-[(3-chloro-4-fluorophenyl)amino]-7-[(S)-(tetrahydrofuran-2-yl)methoxy]quinazoline
• 英文别名: 4-N-(3-chloro-4-fluorophenyl)-7-[[(2S)-oxolan-2-yl]methoxy]quinazoline-4,6-diamine
• CAS: 439081-59-1
• 化学式: C₁₉H₁₈ClFN₄O₂
• 分子量: 388.829
• InChiKey: NMYUQRVTMBHNKE-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  82.3
• 氢给体数：
  2
• 氢受体数：
  7

文献信息

• Quinazoline derivatives and phamaceutical compositions containing them
  申请人：——

  公开号：US20020173509A1

  公开（公告）日：2002-11-21

  A compound of general formula I 1 wherein: R a is a benzyl, 1-phenylethyl, or 3-chloro-4-fluorophenyl group; R b is a dimethylamino, N-methyl-N-ethylamino, diethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetrahydrofuran-3-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetrahydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and R c is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group, or a tautomer, stereoisomer, or salt thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.

  通用式I1的化合物，其中： R是苄基、1-苯乙基或3-氯-4-氟苯基基团； R₂是二甲胺基、N-甲基-N-乙基胺基、二乙胺基、N-甲基-N-异丙基胺基、N-甲基-N-环丙基胺基、N-甲基-N-(2-甲氧乙基)胺基、N-乙基-N-(2-甲氧乙基)胺基、双(2-甲氧乙基)胺基、吗啉基、N-甲基-N-(三氢呋喃-3-基)胺基、N-甲基-N-(三氢呋喃-2-甲基)胺基、N-甲基-N-(三氢呋喃-3-甲基)胺基、N-甲基-N-(四氢吡喃-4-基)胺基或N-甲基-N-(四氢吡喃-4-甲基)胺基； R₃是环丙基甲氧基、环丁基氧基、环戊基氧基、三氢呋喃-3-基氧基、三氢呋喃-2-甲氧基、三氢呋喃-3-甲氧基、四氢吡喃-4-基氧基或四氢吡喃-4-甲氧基基团，或其互变异构体、立体异构体或盐，特别是与具有有价值的药理学性质的无机或有机酸或碱形成的生理学上可接受的盐，特别是对酪氨酸激酶介导的信号转导具有抑制作用的盐，在疾病治疗中的应用，特别是肿瘤性疾病和肺部及气道疾病的治疗，以及其制备。
• [DE] CHINAZOLINDERIVATE, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL, DEREN VERWENDUNG UND VERFAHREN ZU IHRER HERSTELLUNG<br/>[EN] QUINAZOLINE DERIVATIVES, MEDICAMENTS CONTAINING SAID COMPOUNDS, THEIR UTILIZATION AND METHOD FOR THE PRODUCTION THEREOF<br/>[FR] DERIVES DE LA QUINAZOLINE, MEDICAMENTS CONTENANT CES COMPOSES, LEUR UTILISATION ET LEUR PROCEDE DE FABRICATION
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2002050043A1

  公开（公告）日：2002-06-27

  Die vorliegende Erfindung betrifft Chinazolinderivate der allgemeinen Formel (I), in der Ra, Rb, und Rc wie im Anspruch 1 definiert sind, deren Tautomere, deren Stereoisomere und deren Salze, insbesondere deren physiologisch verträgliche Salze mit anorganischen oder organischen Säuren, welche wertvolle pharmakologische Eigenschaften aufweisen, insbesondere eine Hemmwirkung auf die durch Tyrosinkinasen vermittelte Signaltrunsduktion, deren Verwendung zur Behandlung von Krankheiten, insbesondere von Tumorerkrankungen, von Erkrankungen der Lunge und der Atemwege und deren Herstellung.

  本发明涉及通式（I）中的Chinazolinderivate，其中Ra，Rb和Rc如权利要求1中所定义，其互变异构体，立体异构体和盐，特别是与无机或有机酸形成的生理相容性盐，具有有价值的药理特性，特别是通过酪氨酸激酶介导的信号传导具有抑制作用，其用于治疗疾病，特别是肿瘤疾病，肺和呼吸道疾病以及其制备。
• Quinazoline derivatives and pharmaceutical compositions containing them
  申请人：Himmelsbach Frank

  公开号：US20060100223A1

  公开（公告）日：2006-05-11

  A compound of general formula I wherein: R a is a benzyl, 1-phenylethyl, or 3-chloro-4-fluorophenyl group; R b is a dimethylamino, N-methyl-N-ethylamino, diethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetrahydrofuran-3-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetrahydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and R c is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group, or a tautomer, stereoisomer, or salt thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.

  化合物的一般式I，其中：R为苄基，1-苯乙基或3-氯-4-氟苯基基团；Rb为二甲基氨基，N-甲基-N-乙基氨基，二乙基氨基，N-甲基-N-异丙基氨基，N-甲基-N-环丙基氨基，N-甲基-N-(2-甲氧基乙基)氨基，N-乙基-N-(2-甲氧基乙基)氨基，双(2-甲氧基乙基)氨基，吗啡环氧基，N-甲基-N-(四氢呋喃-3-基)氨基，N-甲基-N-(四氢呋喃-2-甲基)氨基，N-甲基-N-(四氢呋喃-3-甲基)氨基，N-甲基-N-(四氢吡喃-4-基)氨基或N-甲基-N-(四氢吡喃-4-甲基)氨基基团；以及Rc为环丙基甲氧基，环丁氧基，环戊氧基，四氢呋喃-3-氧基，四氢呋喃-2-甲氧基，四氢呋喃-3-甲氧基，四氢吡喃-4-氧基或四氢吡喃-4-甲氧基基团，或其互变异构体、立体异构体或盐，特别是与无机或有机酸或碱的生理上可接受的盐，具有有价值的药理学性质，特别是对由酪氨酸激酶介导的信号转导具有抑制作用，其在疾病治疗中的应用，特别是肿瘤性疾病和肺部和呼吸道疾病的治疗，以及其制备。
• QUINAZOLINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：HIMMELSBACH Frank

  公开号：US20100010023A1

  公开（公告）日：2010-01-14

  A compound of general formula I wherein: R a is a benzyl, 1-phenylethyl, or 3-chloro-4-fluorophenyl group; R b is a dimethylamino, N-methyl-N-ethylamino, diethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetra-hydrofuran-3-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetra-hydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and R c is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group, or a tautomer, stereoisomer, or salt thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.

  化合物I的一般式为：其中：R为苄基、1-苯乙基或3-氯-4-氟苯基基团；Rb为二甲基氨基、N-甲基-N-乙基氨基、二乙基氨基、N-甲基-N-异丙基氨基、N-甲基-N-环丙基氨基、N-甲基-N-(2-甲氧基乙基)氨基、N-乙基-N-(2-甲氧基乙基)氨基、双(2-甲氧基乙基)氨基、吗啉基、N-甲基-N-(四氢呋喃-3-基)氨基、N-甲基-N-(四氢呋喃-2-甲基)氨基、N-甲基-N-(四氢呋喃-3-甲基)氨基、N-甲基-N-(四氢吡喃-4-基)氨基或N-甲基-N-(四氢吡喃-4-甲基)氨基基团；且Rc为环丙基甲氧基、环丁氧基、环戊氧基、四氢呋喃-3-基氧基、四氢呋喃-2-甲基氧基、四氢呋喃-3-甲基氧基、四氢吡喃-4-基氧基或四氢吡喃-4-甲基氧基基团，或其互变异构体、立体异构体或盐，特别是与无机或有机酸或碱形成的生理上可接受的盐，具有有价值的药理学特性，特别是对酪氨酸激酶介导的信号转导具有抑制作用，在治疗疾病，特别是肿瘤性疾病和肺部和呼吸道疾病以及其制备方面的用途。
• METHODS OF TREATING DISEASES USING QUINAZOLINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：HIMMELSBACH Frank

  公开号：US20110046168A1

  公开（公告）日：2011-02-24

  A compound of general formula I wherein: R a is a benzyl, 1-phenylethyl, or 3-chloro-4-fluorophenyl group; R b is a dimethylamino, N-methyl-N-ethylamino, diethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetrahydrofuran-3-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetrahydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and R c is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group, or a tautomer, stereoisomer, or salt thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.

  通式I的化合物，其中：R是苯甲基、1-苯乙基或3-氯-4-氟苯基基团；Rb是二甲基氨基、N-甲基-N-乙基氨基、二乙基氨基、N-甲基-N-异丙基氨基、N-甲基-N-环丙基氨基、N-甲基-N-(2-甲氧基乙基)氨基、N-乙基-N-(2-甲氧基乙基)氨基、双(2-甲氧基乙基)氨基、吗啡啉、N-甲基-N-(四氢呋喃-3-基)氨基、N-甲基-N-(四氢呋喃-2-甲基)氨基、N-甲基-N-(四氢呋喃-3-甲基)氨基、N-甲基-N-(四氢吡喃-4-基)氨基或N-甲基-N-(四氢吡喃-4-甲基)氨基基团；Rc是环丙基甲氧基、环丁氧基、环戊氧基、四氢呋喃-3-氧基、四氢呋喃-2-甲氧基、四氢呋喃-3-甲氧基、四氢吡喃-4-氧基或四氢吡喃-4-甲氧基基团，或其互变异构体、立体异构体或盐，特别是与无机或有机酸或碱的生理上可接受的盐，具有有价值的药理学特性，特别是对酪氨酸激酶介导的信号转导具有抑制作用，它们在疾病治疗中的应用，特别是肿瘤性疾病和肺部和呼吸道疾病的治疗，以及其制备。