3-chloro-4-(pyridin-2-yloxy)aniline | 179687-67-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-chloro-4-(pyridin-2-yloxy)aniline
• 英文别名: 3-chloro-4-pyridin-2-yloxyaniline
• CAS: 179687-67-3
• 化学式: C₁₁H₉ClN₂O
• 分子量: 220.658
• InChiKey: ISOUIEYTFVMZSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  48.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-chloro-4-(pyridin-2-yloxy)aniline 、 methyl 2-(4-amino-6-chloropyrimidin-5-yl)-4,5-dihydrooxazol-4-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 水 、 叔丁醇 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Pyrimidine-Based Dual Inhibitors of Human Epidermal Growth Factor Receptor 1 (HER-1) and HER-2 Tyrosine Kinases

  摘要：

  A novel series of N-4-(3-chlorophenyl)-5-(oxazol-2-yl)pyrimidine-4,6-diamines were synthesized and evaluated as dual inhibitors of HER-1/HER-2 tyrosine kinases. In contrast to the currently approved HER-2-targeted agent (lapatinib, 1), our irreversible HER-1/HER-2 inhibitors have the potential to overcome the clinically relevant and mutation-induced drug resistance. The selected compound (19a) showed excellent inhibitory activity toward HER-1/HER-2 tyrosine lcinases with selectivity over 20 other kinases and inhibited the proliferation of both cancer cell types: lapatinib-sensitive cell lines (SK-Br3, MDA-MB-175, and N87) and lapatinib-resistant cell lines (MDA-MB-453, H1781, and H1975). The excellent pharmacokinetic profiles of 19a in mice and rats led us to further investigation of a novel therapeutic agent for HER-2-targeting treatment of solid tumors, especially HER-2-positive breast/gastric cancer and HER-2-mutated lung cancer.

  DOI：

  10.1021/jm201758g
• 作为产物：
  描述：

  2-(2-chloro-4-nitrophenoxy)pyridine 在 platinum on activated charcoal 、 氢气 作用下， 以 乙醇 为溶剂， 生成 3-chloro-4-(pyridin-2-yloxy)aniline
  参考文献：
  名称：

  Synthesis and evaluation of aniline headgroups for alkynyl thienopyrimidine dual EGFR/ErbB-2 kinase inhibitors

  摘要：

  Aniline 'headgroups' were synthesized and incorporated into an alkynyl thienopyrimidine series of EGFR and ErbB-2 inhibitors. Potent inhibition of enzyme activity and cellular proliferation was observed. In certain instances, protein binding was reduced and oral exposure was found to be somewhat improved relative to compounds containing the reference aniline. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.01.080

文献信息

• [EN] QUINAZOLINE DERIVATIVES AS ERBB RECEPTOR TYROSINE KINASES<br/>[FR] DERIVES DE QUINAZOLINE UTILISES COMME TYROSINE KINASES DU RECEPTEUR ERBB
  申请人：ASTRAZENECA AB

  公开号：WO2005118572A1

  公开（公告）日：2005-12-15

  The invention concerns quinazoline derivatives of the formula (I), wherein each of R1, R2, R3, R4, R5, R6, R7, X1, Q1, m and n have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosine kinases.

  该发明涉及公式(I)的喹唑啉衍生物，其中R1、R2、R3、R4、R5、R6、R7、X1、Q1、m和n中的每个都具有描述中定义的任意含义；它们的制备方法，含有它们的药物组合物以及它们在制造用作抗增殖剂的药物中的用途，用于预防或治疗对erbB受体酪氨酸激酶抑制敏感的肿瘤。
• Substituted bicyclic derivatives for the treatment of abnormal cell growth
  申请人：——

  公开号：US20020169165A1

  公开（公告）日：2002-11-14

  The invention relates to compounds of the formula 1 1 and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein R 1 , R 3 , R 4 , R 5 , R 11 , m and p are as defined herein. The invention also relates to methods of treating abnormal cell growth in mammals by administering the compounds of formula 1 and to pharmaceutical compositions for treating such disorders which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.

  该发明涉及公式11的化合物，以及其药学上可接受的盐、前药和溶剂化物，其中R1、R3、R4、R5、R11、m和p如本文所定义。该发明还涉及通过给予公式1的化合物治疗哺乳动物的异常细胞增长的方法，并且涉及用含有公式1的化合物的制药组合物治疗这种疾病的方法。该发明还涉及制备公式1的化合物的方法。
• [EN] ANILINE DERIVATIVES<br/>[FR] DERIVES DE L'ANILINE
  申请人：ZENECA LIMITED

  公开号：WO1996015118A1

  公开（公告）日：1996-05-23

  (EN) The invention concerns aniline derivatives of formula (I) wherein m is 1, 2 or 3 and each R1 includes halogeno, hydroxy, amino, hydroxyamino, ureido, trifluoromethoxy and (1-4C)alkyl; n is 0, 1, 2 or 3 and each R2 includes halogeno, trifluoromethyl, hydroxy, amino, nitro, cyano and (1-4C)alkyl; X is a group of the formula CO, C(R3)2, CH(OR3), C(R3)2-C(R3)2, C(R3)=C(R3), C=C, CH(CN), O, S, SO, SO2, CONR3, SO2NR3, NR3CO, NR3SO2, OC(R3)2, SC(R3)2, C(R3)2O or C(R3)2S wherein each R3 is independently hydrogen or (1-4C)alkyl; and Q is a phenyl or naphthyl group or a 5- or 6-membered heteroaryl moiety containing 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulphur; or a pharmaceutically-acceptable salt thereof; processes for their preparation, pharmaceutical compositions containing them, and the use of the receptor tyrosine kinase inhibitory properties of the compounds in the treatment of proliferative disease such as cancer.(FR) L'invention concerne des dérivés de l'aniline de la formule (I). Dans cette formule, m vaut 1, 2 ou 3 et chaque R1 représente halogéno, hydroxy, amino, hydroxyamino, uréido, trifluorométhoxy et (1-4C) alkyle; n vaut 0, 1, 2 ou 3 et chaque R2 représente halogéno, trifluorométhyle, hydroxy, amino, nitro, cyano et (1-4C) alkyle; X est un groupe de la formule CO, C(R3)2, CH(OR3), C(R3)2-C(R3)2, C(R3)=C(R3), C=C, CH(CH), O, S, SO, SO2, CONR3, SO2NR3, NR3CO, NR3CO2, OC(R3)2, SC(R3)2, C(R3)2O ou C(R3)2S, où chaque R3 est indépendamment hydrogène ou (1-4C) alkyle; et Q est un groupe de phényle ou de naphthyle ou une fraction hétéroarylique à 5 ou 6 éléments comprenant 1, 2 ou 3 hétéroatomes choisis parmi l'oxygène, l'azote et le soufre. L'invention concerne également un sel de la présente formule qui soit acceptable sur le plan pharmaceutique; des procédés pour leur préparation, des compositions pharmaceutiques à base de ces substances, et l'utilisation des propriétés inhibitrices du récepteur de tyrosine-kinase des composés dans le traitement de maladies à évolution chronique telles que le cancer.

  本发明涉及公式（I）的苯胺衍生物，其中m为1、2或3，每个R1包括卤素、羟基、氨基、羟氨基、脲基、三氟甲氧基和（1-4C）烷基；n为0、1、2或3，每个R2包括卤素、三氟甲基、羟基、氨基、硝基、氰基和（1-4C）烷基；X是公式CO、C（R3）2、CH（OR3）、C（R3）2-C（R3）2、C（R3）=C（R3）、C=C、CH（CN）、O、S、SO、SO2、CONR3、SO2NR3、NR3CO、NR3SO2、OC（R3）2、SC（R3）2、C（R3）2O或C（R3）2S的基团，其中每个R3独立地为氢或（1-4C）烷基；Q是苯基或萘基或包含1、2或3个氧、氮和硫杂原子的5或6元杂环基；或其药学上可接受的盐；制备它们的方法，含有它们的制药组合物，以及利用化合物的受体酪氨酸激酶抑制性质治疗增殖性疾病，如癌症。
• Quinazoline derivatives as antitumor agents
  申请人：Hennequin Francois Andre Laurent

  公开号：US20050043336A1

  公开（公告）日：2005-02-24

  The invention concerns quinazoline derivatives of Formula (I); wherein each of Q 1 , Q 2 , Z, R 1 , R 2 , R 3 , and m have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosin kinases.

  该发明涉及公式（I）的喹唑啉衍生物；其中Q1，Q2，Z，R1，R2，R3和m的每个定义在说明中具有任何意义；它们的制备过程，包含它们的制药组合物以及它们在制造对erbB受体酪氨酸激酶抑制敏感的肿瘤的预防或治疗药物中的使用。
• Quinazoline Derivatives as Erbb Receptor Tyrosine kinases
  申请人：Bradbury Hugh Robert

  公开号：US20070232607A1

  公开（公告）日：2007-10-04

  The invention concerns quinazoline derivatives of the formula (I), wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X 1 , Q 1 , m and n have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosine kinases.

  这项发明涉及公式（I）的喹唑啉衍生物，其中R1、R2、R3、R4、R5、R6、R7、X1、Q1、m和n中的每一个都具有描述中定义的任何含义；它们的制备过程，含有它们的制药组合物以及它们在制造用作抗增殖剂的药物的过程中的使用，用于预防或治疗对erbB受体酪氨酸激酶抑制敏感的肿瘤。