anti-4-[6-amino-5-(ethoxyimino-methyl)-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester | 916667-03-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: anti-4-[6-amino-5-(ethoxyimino-methyl)-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: 4-[6-Amino-5-(ethoxyimino-methyl)-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester；tert-butyl 4-[6-amino-5-[(E)-ethoxyiminomethyl]pyrimidin-4-yl]piperazine-1-carboxylate
• CAS: 916667-03-3
• 化学式: C₁₆H₂₆N₆O₃
• 分子量: 350.421
• InChiKey: DMHOEHVLZWGDII-KEBDBYFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  anti-4-[6-amino-5-(ethoxyimino-methyl)-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  SYNERGISTIC MODULATION OF FLT3 KINASE USING AMINOPYRIMIDINES KINASE MODULATORS

  摘要：

  这项发明涉及一种抑制FLT3酪氨酸激酶活性或表达或减少细胞或受试者中FLT3激酶活性或表达的方法，包括给予一种法尼基转移酶抑制剂和一种从式I′的氨基嘧啶化合物中选择的FLT3激酶抑制剂：其中R3、B、Z、r和R1如本文所定义。本发明涵盖了用于治疗处于发展细胞增殖障碍或与FLT3有关的障碍风险（或易感）的受试者的预防和治疗方法。

  公开号：

  US20060281755A1
• 作为产物：
  描述：

  4-氨基-6-氯-5-醛基嘧啶 在 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 anti-4-[6-amino-5-(ethoxyimino-methyl)-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  4-Amino-6-piperazin-1-yl-pyrimidine-5-carbaldehyde oximes as potent FLT-3 inhibitors

  摘要：

  A series of 4-amino-6-piperazin- I -yl-pyrimi dine- 5-carbaldehyde oximes has been discovered and developed as potent FLT3 tyrosine kinase inhibitors. The series exhibited potent antiproliferative activity against both an FLT3 ITD-mutated human leukemic cell line as well as a wild-type FLT3 BaF3 expressed cell line. The structure-activity relationship of this class of compounds is described. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.06.046

文献信息

• AMINOPYRIMIDINES AS KINASE MODULATORS
  申请人：Gaul David Michael

  公开号：US20070021435A1

  公开（公告）日：2007-01-25

  The invention is directed to aminopyrimidine compounds of Formula I: where R 3 , B, Z, r and R 1 are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of FLT3 and/or c-kit and/or TrkB, the use of such compounds to reduce or inhibit kinase activity of FLT3 and/or c-kit and/or TrkB in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3 and/or c-kit and/or TrkB. The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.

  本发明涉及式I的氨基嘧啶化合物：其中R3、B、Z、r和R1的定义如本文所述，所述化合物的用途为蛋白酪氨酸激酶调节剂，特别是FLT3和/或c-kit和/或TrkB的抑制剂，所述化合物的用途为在细胞或受体中减少或抑制FLT3和/或c-kit和/或TrkB的激酶活性，并用于预防或治疗与FLT3和/或c-kit和/或TrkB相关的细胞增殖性疾病和/或疾病。本发明还涉及包含本发明化合物的药物组合物以及治疗癌症和其他细胞增殖性疾病的方法。
• WO2006/135719
  申请人：——

  公开号：——

  公开（公告）日：——
• SYNERGISTIC MODULATION OF FLT3 KINASE USING AMINOPYRIMIDINES KINASE MODULATORS AND A FARNESYL TRANSFERASE INHIBITOR
  申请人：Janssen Pharmaceutica NV

  公开号：EP1901745A2

  公开（公告）日：2008-03-26
• [EN] SYNERGISTIC MODULATION OF FLT3 KINASE USING AMINOPYRIMIDINES KINASE MODULATORS<br/>[FR] MODULATION SYNERGIQUE DE LA KINASE FLT3 A L'AIDE DE MODULATEURS DE KINASE SELECTIONNES PARMI DES AMINOPYRIMIDINES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2006135713A2

  公开（公告）日：2006-12-21

  [EN] The invention is directed to a method of inhibiting FLT3 tyrosine kinase activity or expression or reducing FLT3 kinase activity or expression in a cell or a subject comprising the administration of a farnesyl transferase inhibitor and a FLT3 kinase inhibitor selected from aminopyrimidine compounds of Formula I': where R₃, B, Z, r and R₁ are as defined herein. Included within the present invention is both prophylactic and therapeutic methods for treating a subject at risk of (or susceptible to) developing a cell proliferative disorder or a disorder related to FLT3.
  [FR] L'invention concerne un procédé visant à inhiber l'activité ou l'expression de la tyrosine kinase FLT3 ou à réduire l'activité ou l'expression de la kinase FLT3 dans une cellule ou chez un sujet, ce procédé consistant à administrer un inhibiteur de la farnésyle-transférase et un inhibiteur de la kinase FLT3 sélectionné parmi des composés d'aminopyrimidine de formule I', dans laquelle R₃, B, Z, r et R₁ sont tels que définis dans la demande. L'invention concerne également des méthodes prophylactiques et thérapeutiques de traitement d'un sujet risquant (ou susceptible) de développer un trouble lié à la prolifération cellulaire ou un trouble lié à FLT3.
• [EN] AMINOPYRIMIDINES AS KINASE MODULATORS<br/>[FR] AMINOPYRIMIDINES COMME MODULATEURS DE KINASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2006135719A1

  公开（公告）日：2006-12-21

  [EN] Abstract The invention is directed to aminopyrimidine compounds of Formula I: where R3, B, Z, r and R1 are as defined herein, the use of such compounds as protein tyrosine kinase modulators, particularly inhibitors of FLT3 and/or c-kit and/or TrkB, the use of such compounds to reduce or inhibit kinase activity of FLT3 and/or c-kit and/or TrkB in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3 and/or c-kit and/or TrkB . The present invention is further directed to pharmaceutical compositions comprising the compounds of the present invention and to methods for treating conditions such as cancers and other cell proliferative disorders.
  [FR] La présente invention concerne des composés d'aminopyrimidines de formule I : où R3, B, Z, r et R1 sont tels que définis ici. L'invention décrit l'utilisation de tels composés comme modulateurs de la protéine tyrosine kinase, spécialement des inhibiteurs de FLT3 et/ou de c-kit et/ou de TrkB, l'utilisation de tels composés pour réduire ou inhiber l'activité de la kinase de FLT3 et/ou de c-kit et/ou de TrkB dans une cellule ou un sujet, ainsi que l'utilisation de tels composés pour empêcher ou traiter chez un sujet un trouble de prolifération cellulaire et/ou des troubles reliés à FLT3 et/ou à c-kit et/ou à TrkB. La présente invention vise en outre des compositions pharmaceutiques qui comprennent les composés de la présente invention et des procédés pour traiter des troubles tels que des cancers et autres troubles de prolifération cellulaire.