3-(2-(4-(4-isopropylpiperazin-1-yl)-2-methoxyphenylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)thiophene-2-carboxamide | 1123163-15-4

• 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: 3-(2-(4-(4-isopropylpiperazin-1-yl)-2-methoxyphenylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)thiophene-2-carboxamide
• 英文别名: 3-[[2-[2-methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]thiophene-2-carboxamide
• CAS: 1123163-15-4
• 化学式: C₂₅H₃₀N₈O₂S
• 分子量: 506.632
• InChiKey: PGLGFLNSPUHDGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  153
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-(2-(4-(4-isopropylpiperazin-1-yl)-2-methoxyphenylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)thiophene-2-carboxamide 在 盐酸 作用下， 以 水 为溶剂， 生成 8-[2-Methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-12-thia-5,7,9,16-tetrazatetracyclo[7.7.0.02,6.011,15]hexadeca-1(16),2(6),3,7,11(15),13-hexaen-10-one
  参考文献：
  名称：

  Optimization of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine inhibitors of IGF-1R: Elimination of an acid-mediated decomposition pathway

  摘要：

  Initial evaluation of a series 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines revealed a C(10) carboxamide was preferred for sub-micromolar in vitro potency against IGF-1R. Subsequent solution stability studies with 1 revealed a susceptibility toward acid-induced intramolecular cyclization with the C(10) carboxamide. Herein, we describe several successful approaches toward generating both potent and acid-stable inhibitors of IGF-1R within the 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine template. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.065
• 作为产物：
  描述：

  3-[[2-[2-Methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidin-4-yl]amino]thiophene-2-carboxamide 在 水 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 3-(2-(4-(4-isopropylpiperazin-1-yl)-2-methoxyphenylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)thiophene-2-carboxamide
  参考文献：
  名称：

  Optimization of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine inhibitors of IGF-1R: Elimination of an acid-mediated decomposition pathway

  摘要：

  Initial evaluation of a series 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines revealed a C(10) carboxamide was preferred for sub-micromolar in vitro potency against IGF-1R. Subsequent solution stability studies with 1 revealed a susceptibility toward acid-induced intramolecular cyclization with the C(10) carboxamide. Herein, we describe several successful approaches toward generating both potent and acid-stable inhibitors of IGF-1R within the 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine template. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.11.065

文献信息

• Optimization of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine inhibitors of IGF-1R: Elimination of an acid-mediated decomposition pathway
  作者：Stanley D. Chamberlain、Anikó M. Redman、Samarjit Patnaik、Keith Brickhouse、Yen-Chiat Chew、Felix Deanda、Roseanne Gerding、Huangshu Lei、Ganesh Moorthy、Mark Patrick、Kirk L. Stevens、Joseph W. Wilson、J. Brad Shotwell

  DOI：10.1016/j.bmcl.2008.11.065

  日期：2009.1

  Initial evaluation of a series 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines revealed a C(10) carboxamide was preferred for sub-micromolar in vitro potency against IGF-1R. Subsequent solution stability studies with 1 revealed a susceptibility toward acid-induced intramolecular cyclization with the C(10) carboxamide. Herein, we describe several successful approaches toward generating both potent and acid-stable inhibitors of IGF-1R within the 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine template. (C) 2008 Elsevier Ltd. All rights reserved.