N-{3-cyclopropyl-4-[(4-methylpiperazin-1-yl)methyl]phenyl}-3-iodo-4-methylbenzamide | 1229622-64-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-{3-cyclopropyl-4-[(4-methylpiperazin-1-yl)methyl]phenyl}-3-iodo-4-methylbenzamide
• 英文别名: N-(3-cyclopropyl-4-((4-methylpiperazin-1-yl)methyl)phenyl)-3-iodo-4-methylbenzamide；N-[3-cyclopropyl-4-[(4-methylpiperazin-1-yl)methyl]phenyl]-3-iodo-4-methylbenzamide
• CAS: 1229622-64-3
• 化学式: C₂₃H₂₈IN₃O
• 分子量: 489.399
• InChiKey: NLNQRXDTBJRQCS-UHFFFAOYSA-N

物化性质

• 沸点：
  507.5±50.0 °C(Predicted)
• 密度：
  1.473±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-乙炔咪唑并[1,2-b]吡嗪 、 N-{3-cyclopropyl-4-[(4-methylpiperazin-1-yl)methyl]phenyl}-3-iodo-4-methylbenzamide 在 copper(l) iodide 、 四(三苯基膦)钯 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 N-(3-cyclopropyl-4((4-methylpiperazin-1-yl)methyl)phenyl)-3-(imidazo[1,2-b] pyridazin-3-ylethynyl)-4-methylbenzamide
  参考文献：
  名称：

  Discovery of 3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a Potent, Orally Active Pan-Inhibitor of Breakpoint Cluster Region-Abelson (BCR-ABL) Kinase Including the T315I Gatekeeper Mutant

  摘要：

  In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of I1e315 side chain. Extensive SAR studies led to the discovery of development candidate 20g (AP24534), which inhibited the kinase activity of both native BCR-ABL and the T315I mutant with low nM IC(50)s, and potently inhibited proliferation of corresponding Ba/F3-derived cell lines. Daily oral administration of 20g significantly prolonged survival of mice injected intravenously with BCR-ABL(T315I) expressing Ba/F3 cells. These data, coupled with a favorable ADME profile, support the potential of 20g to be an effective treatment for CM L, including patients refractory to all currently approved therapies.

  DOI：

  10.1021/jm100395q
• 作为产物：
  描述：

  3-cyclopropyl-4-(4-methyl-piperazin-1-ylmethyl)-phenylamine 、 3-碘-4-甲基苯甲酰氯 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 N-{3-cyclopropyl-4-[(4-methylpiperazin-1-yl)methyl]phenyl}-3-iodo-4-methylbenzamide
  参考文献：
  名称：

  Discovery of 3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a Potent, Orally Active Pan-Inhibitor of Breakpoint Cluster Region-Abelson (BCR-ABL) Kinase Including the T315I Gatekeeper Mutant

  摘要：

  In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of I1e315 side chain. Extensive SAR studies led to the discovery of development candidate 20g (AP24534), which inhibited the kinase activity of both native BCR-ABL and the T315I mutant with low nM IC(50)s, and potently inhibited proliferation of corresponding Ba/F3-derived cell lines. Daily oral administration of 20g significantly prolonged survival of mice injected intravenously with BCR-ABL(T315I) expressing Ba/F3 cells. These data, coupled with a favorable ADME profile, support the potential of 20g to be an effective treatment for CM L, including patients refractory to all currently approved therapies.

  DOI：

  10.1021/jm100395q

文献信息

• [EN] METHODS AND COMPOSITIONS FOR RAF KINASE MEDIATED DISEASES<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR LE TRAITEMENT DE MALADIES MÉDIÉES PAR LA KINASE RAF
  申请人：ARIAD PHARMA INC

  公开号：WO2013162727A1

  公开（公告）日：2013-10-31

  The invention discloses methods and compositions for treating or preventing RAF kinase mediated diseases or conditions by administering a compound of Formula 1: or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the variables are defined as herein.

  该发明揭示了通过给予化合物Formula 1或其药学上可接受的盐、溶剂或水合物来治疗或预防由RAF激酶介导的疾病或症状的方法和组合物，其中变量如本文所定义。
• Bicyclic heteroaryl compounds
  申请人：Zou Dong

  公开号：US20070191376A1

  公开（公告）日：2007-08-16

  This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  本发明涉及通式如下的化合物：其中变量基团如本文所定义，以及它们的制备和使用。
• Monocyclic Heteroaryl compounds
  申请人：ARIAD Pharmaceuticals, Inc.

  公开号：US08278307B2

  公开（公告）日：2012-10-02

  This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  本发明涉及以下通式的化合物：其中变量基团如本文所定义，并涉及其制备和应用。
• Substituted acetylenic imidazo[1,2-B]pyridazine compounds as kinase inhibitors
  申请人：ARIAD Pharmaceuticals, Inc.

  公开号：US08114874B2

  公开（公告）日：2012-02-14

  This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use. In particular, the compounds include embodiments in which Ring T is an imidazo[1,2-b]pyridazine ring system, Rings A and B are each aryl and L1 is —C(O)NR1— or —NR1C(O)—. Uses for the compounds and for compositions containing them include treatment of cancer and other diseases mediated by protein kinases.

  本发明涉及以下通式的化合物：其中变量基团如本文所定义，以及它们的制备和使用。特别是，该化合物包括环T为咪唑并[1,2-b]吡嗪环系统，环A和环B均为芳基，L1为—C(O)NR1—或—NR1C(O)—的实施例。该化合物和含有它们的组合物的用途包括治疗癌症和其他由蛋白激酶介导的疾病。
• Bicyclic Heteroaryl Compounds
  申请人：Zou Dong

  公开号：US20120135986A1

  公开（公告）日：2012-05-31

  This invention relates to compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.

  本发明涉及一般公式中的化合物：其中变量基团如本文所定义，并涉及它们的制备和使用。