tert-butyl 6-[(2,4-difluorophenyl)methyl]-3,3-dimethyl-1H,2H,3H-pyrrolo[3,2-c]pyridine-1-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: tert-butyl 6-[(2,4-difluorophenyl)methyl]-3,3-dimethyl-1H,2H,3H-pyrrolo[3,2-c]pyridine-1-carboxylate
• 英文别名: tert-butyl 6-[(2,4-difluorophenyl)methyl]-3,3-dimethyl-2H-pyrrolo[3,2-c]pyridine-1-carboxylate
• 化学式: C₂₁H₂₄F₂N₂O₂
• 分子量: 374.431
• InChiKey: GMMLFFAPGWJTDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 6-[(2,4-difluorophenyl)methyl]-3,3-dimethyl-1H,2H,3H-pyrrolo[3,2-c]pyridine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 18.0h， 以100%的产率得到6-[(2,4-difluorophenyl)methyl]-3,3-dimethyl-1H,2H,3H-pyrrolo[3,2-c]pyridine hydrochloride
  参考文献：
  名称：

  Discovery of a Potent Nonpeptidomimetic, Small-Molecule Antagonist of Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) and X-Linked Inhibitor of Apoptosis Protein (XIAP)

  摘要：

  XIAP and cIAP1 are members of the inhibitor of apoptosis protein (IAP) family and are key regulators of anti-apoptotic and pro-survival signaling pathways. Over expression Of IAPs occurs in various cancers and has been associated with tumor progression and resistance to treatment. Structure-based drug design (SBDD) guided by structural information from X-ray crystallography, computational studies, and NMR solution conformational analysis was successfully applied to.a fragment-derived lead resulting, in AT-IAP, a potent, orally bioavailable, dual antagonist of XIAP and cIAP1 and a structurally novel chemical probe for LAP biology.

  DOI：

  10.1021/acs.jmedchem.6b01877
• 作为产物：
  描述：

  bromozinc(1+),2,4-difluoro-1-methanidylbenzene 、 6-chloro-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester 在 (1,3-diisopropylimidazol-2-ylidene)(3-chloropyridyl)palladium(II) dichloride 、 lithium bromide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 为溶剂， 反应 24.0h， 以51%的产率得到tert-butyl 6-[(2,4-difluorophenyl)methyl]-3,3-dimethyl-1H,2H,3H-pyrrolo[3,2-c]pyridine-1-carboxylate
  参考文献：
  名称：

  Discovery of a Potent Nonpeptidomimetic, Small-Molecule Antagonist of Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) and X-Linked Inhibitor of Apoptosis Protein (XIAP)

  摘要：

  XIAP and cIAP1 are members of the inhibitor of apoptosis protein (IAP) family and are key regulators of anti-apoptotic and pro-survival signaling pathways. Over expression Of IAPs occurs in various cancers and has been associated with tumor progression and resistance to treatment. Structure-based drug design (SBDD) guided by structural information from X-ray crystallography, computational studies, and NMR solution conformational analysis was successfully applied to.a fragment-derived lead resulting, in AT-IAP, a potent, orally bioavailable, dual antagonist of XIAP and cIAP1 and a structurally novel chemical probe for LAP biology.

  DOI：

  10.1021/acs.jmedchem.6b01877

文献信息

• BICYCLIC HETEROCYCLE COMPOUNDS AND THEIR USES IN THERAPY
  申请人：Woolford Alison Jo-Anne

  公开号：US20140179666A1

  公开（公告）日：2014-06-26

  The invention relates to bicyclic heterocycle compounds of formula (I): or tautomeric or stereochemically isomeric forms, N-oxides, pharmaceutically acceptable salts or the solvates thereof; wherein R 1 , R 2a , R 2b , R 3a , R 3b , R 5 , R 6 , R 7 , R 8 , R 9 , p and E are as defined herein; to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

  该发明涉及公式（I）的二环杂环化合物，或其互变异构体或立体化学异构体、N-氧化物、药学上可接受的盐或其溶剂合物；其中R1、R2a、R2b、R3a、R3b、R5、R6、R7、R8、R9、p和E的定义如本文所述；以及包含所述化合物的制药组合物和所述化合物在治疗疾病，例如癌症中的应用。
• EP2699562B1
  申请人：——

  公开号：EP2699562B1

  公开（公告）日：2020-12-23
• US9018214B2
  申请人：——

  公开号：US9018214B2

  公开（公告）日：2015-04-28
• US9676768B2
  申请人：——

  公开号：US9676768B2

  公开（公告）日：2017-06-13
• Discovery of a Potent Nonpeptidomimetic, Small-Molecule Antagonist of Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) and X-Linked Inhibitor of Apoptosis Protein (XIAP)
  作者：Emiliano Tamanini、Ildiko M. Buck、Gianni Chessari、Elisabetta Chiarparin、James E. H. Day、Martyn Frederickson、Charlotte M. Griffiths-Jones、Keisha Hearn、Tom D. Heightman、Aman Iqbal、Christopher N. Johnson、Edward J. Lewis、Vanessa Martins、Torren Peakman、Michael Reader、Sharna J. Rich、George A. Ward、Pamela A. Williams、Nicola E. Wilsher

  DOI：10.1021/acs.jmedchem.6b01877

  日期：2017.6.8

  XIAP and cIAP1 are members of the inhibitor of apoptosis protein (IAP) family and are key regulators of anti-apoptotic and pro-survival signaling pathways. Over expression Of IAPs occurs in various cancers and has been associated with tumor progression and resistance to treatment. Structure-based drug design (SBDD) guided by structural information from X-ray crystallography, computational studies, and NMR solution conformational analysis was successfully applied to.a fragment-derived lead resulting, in AT-IAP, a potent, orally bioavailable, dual antagonist of XIAP and cIAP1 and a structurally novel chemical probe for LAP biology.