tert-butyl 3-methyl-5-[5-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropoxy]-2-phenylpyridin-3-yl]indazole-1-carboxylate | 864770-87-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: tert-butyl 3-methyl-5-[5-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropoxy]-2-phenylpyridin-3-yl]indazole-1-carboxylate
• CAS: 864770-87-6
• 化学式: C₃₈H₄₂N₄O₅
• 分子量: 634.775
• InChiKey: FAUGCNTZXLEZOG-LJAQVGFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  47
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-methyl-5-[5-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropoxy]-2-phenylpyridin-3-yl]indazole-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以78%的产率得到(S)-1-benzyl-2-[5-(3-methyl-1H-indazol-5-yl)-6-phenyl-pyridin-3-yloxy]-ethylamine
  参考文献：
  名称：

  2,3,5-Trisubstituted pyridines as selective AKT inhibitors—Part I: Substitution at 2-position of the core pyridine for ROCK1 selectivity

  摘要：

  2,3,5-Trisubstituted pyridines have been designed as potent AKT inhibitors that are selective against ROCK1 based on the comparison between AKT and ROCK1 structures. Substitution at the 2-position of the core pyridine is the key element to provide selectivity against ROCK1. An X-ray co-crystal structure of 9p in PKA supports the proposed rationale of ROCK1 selectivity. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.064
• 作为产物：
  描述：

  5-[5-((2S)-2-tert-Butoxycarbonylamino-3-phenyl-propoxy)-2-chloro-pyridin-3-yl]-3-methyl-indazole-1-carboxylic Acid Tert-Butyl Ester 、 苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.33h， 以57%的产率得到tert-butyl 3-methyl-5-[5-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropoxy]-2-phenylpyridin-3-yl]indazole-1-carboxylate
  参考文献：
  名称：

  2,3,5-Trisubstituted pyridines as selective AKT inhibitors—Part I: Substitution at 2-position of the core pyridine for ROCK1 selectivity

  摘要：

  2,3,5-Trisubstituted pyridines have been designed as potent AKT inhibitors that are selective against ROCK1 based on the comparison between AKT and ROCK1 structures. Substitution at the 2-position of the core pyridine is the key element to provide selectivity against ROCK1. An X-ray co-crystal structure of 9p in PKA supports the proposed rationale of ROCK1 selectivity. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.064

文献信息

• Inhibitors of akt activity
  申请人：Yamashita S. Dennis

  公开号：US20070185152A1

  公开（公告）日：2007-08-09

  Invented are novel pyridine compounds, the use of such compounds as inhibitors of PKB/AKT kinase activity and in the treatment of cancer and arthritis.

  发明了新型吡啶化合物，这些化合物可用作PKB/AKT激酶活性的抑制剂，并用于癌症和关节炎的治疗。
• 2,3,5-Trisubstituted pyridines as selective AKT inhibitors—Part I: Substitution at 2-position of the core pyridine for ROCK1 selectivity
  作者：Hong Lin、Dennis S. Yamashita、Jin Zeng、Ren Xie、Wenyong Wang、Sirishkumar Nidarmarthy、Juan I. Luengo、Nelson Rhodes、Victoria B. Knick、Anthony E. Choudhry、Zhihong Lai、Elisabeth A. Minthorn、Susan L. Strum、Edgar R. Wood、Patricia A. Elkins、Nestor O. Concha、Dirk A. Heerding

  DOI：10.1016/j.bmcl.2009.11.064

  日期：2010.1

  2,3,5-Trisubstituted pyridines have been designed as potent AKT inhibitors that are selective against ROCK1 based on the comparison between AKT and ROCK1 structures. Substitution at the 2-position of the core pyridine is the key element to provide selectivity against ROCK1. An X-ray co-crystal structure of 9p in PKA supports the proposed rationale of ROCK1 selectivity. (C) 2009 Elsevier Ltd. All rights reserved.