tert-butyl 4-(4-{[5-(aminocarbonyl)-4-(benzylamino)pyrimidin-2-yl]amino}phenyl)piperazine-1-carboxylate | 1042921-57-2

• 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: tert-butyl 4-(4-{[5-(aminocarbonyl)-4-(benzylamino)pyrimidin-2-yl]amino}phenyl)piperazine-1-carboxylate
• 英文别名: Tert-butyl 4-(4-{[5-(aminocarbonyl)-4-(benzylamino)pyrimidin-2-yl]amino}phenyl)piperazin-1-carboxylate；tert-butyl 4-[4-[[4-(benzylamino)-5-carbamoylpyrimidin-2-yl]amino]phenyl]piperazine-1-carboxylate
• CAS: 1042921-57-2
• 化学式: C₂₇H₃₃N₇O₃
• 分子量: 503.604
• InChiKey: RXCIVSKQCYOQPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-{[5-(aminocarbonyl)-4-(benzylamino)pyrimidin-2-yl]amino}phenyl)piperazine-1-carboxylate 在 dioxanic HCl 作用下， 反应 0.5h， 以70%的产率得到4-benzylamino-2-([4-(piperazin-1-yl)phenyl]amino)pyrimidine-5-carboxamide
  参考文献：
  名称：

  Identification of 4-benzylamino-2-[(4-morpholin-4-ylphenyl)amino]pyrimidine-5-carboxamide derivatives as potent and orally bioavailable STAT6 inhibitors

  摘要：

  Signal transducers and activators of transcription 6 (STAT6) is a key regulator of the type 2 helper T (Th2) cell immune response and a potential therapeutic target for allergic diseases such as asthma and atopic diseases. To search for potent and orally bioavailable STAT6 inhibitors, we synthesized a series of 4-benzylaminopyrimidine-5- carboxamide derivatives and evaluated their STAT6 inhibitory activities. Among these compounds, 2-[(4-morpholin-4-ylphenyl)amino]-4-[(2,3,6- trifluorobenzyl)amino]pyrimidine-5-carboxamide (25y, YM-341619, AS1617612) showed potent STAT6 inhibition with an IC(50) of 0.70 nM, and also inhibited Th2 differentiation in mouse spleen T cells induced by interleukin (IL)-4 with an IC(50) of 0.28 nM without affecting type 1 helper T (Th1) cell differentiation induced by IL-12. In addition, compound 25y showed an oral bioavailability of 25% in mouse. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.031
• 作为产物：
  描述：

  4-(benzylamino)-2-chloropyrimidine-5-carboxamide 、 1-Boc-4-(4-氨基苯基)哌嗪 以 N-甲基吡咯烷酮 为溶剂， 生成 tert-butyl 4-(4-{[5-(aminocarbonyl)-4-(benzylamino)pyrimidin-2-yl]amino}phenyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Identification of 4-benzylamino-2-[(4-morpholin-4-ylphenyl)amino]pyrimidine-5-carboxamide derivatives as potent and orally bioavailable STAT6 inhibitors

  摘要：

  Signal transducers and activators of transcription 6 (STAT6) is a key regulator of the type 2 helper T (Th2) cell immune response and a potential therapeutic target for allergic diseases such as asthma and atopic diseases. To search for potent and orally bioavailable STAT6 inhibitors, we synthesized a series of 4-benzylaminopyrimidine-5- carboxamide derivatives and evaluated their STAT6 inhibitory activities. Among these compounds, 2-[(4-morpholin-4-ylphenyl)amino]-4-[(2,3,6- trifluorobenzyl)amino]pyrimidine-5-carboxamide (25y, YM-341619, AS1617612) showed potent STAT6 inhibition with an IC(50) of 0.70 nM, and also inhibited Th2 differentiation in mouse spleen T cells induced by interleukin (IL)-4 with an IC(50) of 0.28 nM without affecting type 1 helper T (Th1) cell differentiation induced by IL-12. In addition, compound 25y showed an oral bioavailability of 25% in mouse. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.031

文献信息

• Diaminopyrimidinecarboxamide derivative
  申请人：Astellas Pharma, Inc.

  公开号：US07449456B2

  公开（公告）日：2008-11-11

  A compound which may be used for the prevention or treatment of respiratory diseases in which STAT 6 is concerned, particularly asthma, chronic obstructive pulmonary disease and the like is provided. A pyrimidine derivative or a salt thereof, which has an arylamino or arylethylamino group which may be substituted with a specified substituent, at the 2-position, amino group substituted with benzyl group or the like, at the 4-position, and carbamoyl group which may be substituted, at the 5-position, is provided.

  提供一种化合物，可用于预防或治疗涉及STAT 6的呼吸系统疾病，特别是哮喘、慢性阻塞性肺疾病等。该化合物是一种嘧啶衍生物或其盐，其在2位具有可以被指定取代基取代的芳基氨基或芳基乙基氨基，4位上具有被苯甲基等基团取代的氨基，5位上具有可以被取代的氨基甲酰基。
• DIAMINOPYRIMIDINECARBOXA MIDE DERIVATIVE
  申请人：Astellas Pharma Inc.

  公开号：EP1518855B1

  公开（公告）日：2011-10-26
• US7449456B2
  申请人：——

  公开号：US7449456B2

  公开（公告）日：2008-11-11