(2R,5S)-4-{2-[6-(4-fluorobenzyl)-3,3-dimethyl-2,3-dihydropyrrolo[3,2-b]pyridin-1-yl]-2-oxoethyl}-2-methyl-5-((R)-3-methylmorpholin-4-ylmethyl)piperazine-1-carboxylic acid tert-butyl ester | 1403904-77-7

• 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: (2R,5S)-4-{2-[6-(4-fluorobenzyl)-3,3-dimethyl-2,3-dihydropyrrolo[3,2-b]pyridin-1-yl]-2-oxoethyl}-2-methyl-5-((R)-3-methylmorpholin-4-ylmethyl)piperazine-1-carboxylic acid tert-butyl ester
• 英文别名: (2R,5S)-4-{2-[6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester；tert-butyl (2R,5S)-4-[2-[6-[(4-fluorophenyl)methyl]-3,3-dimethyl-2H-pyrrolo[3,2-b]pyridin-1-yl]-2-oxoethyl]-2-methyl-5-[[(3R)-3-methylmorpholin-4-yl]methyl]piperazine-1-carboxylate
• CAS: 1403904-77-7
• 化学式: C₃₄H₄₈FN₅O₄
• 分子量: 609.785
• InChiKey: HNWJTZFVPBDWJD-GKAFBRTNSA-N

物化性质

• 沸点：
  725.0±60.0 °C(Predicted)
• 密度：
  1.150±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  78.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,5S)-4-{2-[6-(4-fluorobenzyl)-3,3-dimethyl-2,3-dihydropyrrolo[3,2-b]pyridin-1-yl]-2-oxoethyl}-2-methyl-5-((R)-3-methylmorpholin-4-ylmethyl)piperazine-1-carboxylic acid tert-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 、 乙酸乙酯 为溶剂， 反应 18.0h， 以100%的产率得到1-[6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-[(2R,5R)-5-methyl-2-((R)-3-methyl-morpholin-4-ylmethyl)-piperazin-1-yl]-ethanone 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：

  (2R,5R)-5-(羟甲基)-2-甲基哌嗪-1-羧酸叔丁酯 在 palladium 10% on activated carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 溶剂黄146 、 甲基磺酰氯 、 三乙胺 、 potassium iodide 作用下， 以 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 为溶剂， 20.0~70.0 ℃ 、100.0 kPa 条件下， 反应 40.0h， 生成 (2R,5S)-4-{2-[6-(4-fluorobenzyl)-3,3-dimethyl-2,3-dihydropyrrolo[3,2-b]pyridin-1-yl]-2-oxoethyl}-2-methyl-5-((R)-3-methylmorpholin-4-ylmethyl)piperazine-1-carboxylic acid tert-butyl ester
  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

• [EN] BICYCLIC HETEROCYCLE COMPOUNDS AND THEIR USES IN THERAPY<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES BICYCLIQUES ET LEURS UTILISATIONS EN THÉRAPIE
  申请人：ASTEX THERAPEUTICS LTD

  公开号：WO2012143726A1

  公开（公告）日：2012-10-26

  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 R1, R2a, R2b, R3a, R3b, R5, R6, R7, R8, R9, 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）的双环杂环化合物，或其互变异构体或立体化学同分异构体，N-氧化物，药用盐或其溶剂合物；其中R1、R2a、R2b、R3a、R3b、R5、R6、R7、R8、R9、p和E如本文所定义；以及包含该化合物的药物组合物，以及该化合物在治疗疾病（如癌症）中的用途。
• 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。
• Bicyclic heterocycle compounds and their uses in therapy
  申请人：Woolford Alison Jo-Anne

  公开号：US09018214B2

  公开（公告）日：2015-04-28

  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 R1, R2a, R2b, R3a, R3b, R5, R6, R7, R8, R9, 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）的双环杂环化合物，或其互变异构体、立体异构体、N-氧化物、药学上可接受的盐或其溶剂化物；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将所述化合物用于治疗疾病（例如癌症）的用途。
• 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