(2S)-5-烯丙基-1-((s)-3-(((苄氧基)羰基)氨基)-2-((叔丁氧基羰基)氨基)丙酰基)吡咯烷-2-羧酸甲酯 | 1296138-82-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: (2S)-5-烯丙基-1-((s)-3-(((苄氧基)羰基)氨基)-2-((叔丁氧基羰基)氨基)丙酰基)吡咯烷-2-羧酸甲酯
• 英文名称: methyl (2S)-5-allyl-1-((S)-3-((benzyloxy)carbonylamino)-2-((tert-butoxycarbonyl)amino)propanoyl)pyrrolidine-2-carboxylate
• 英文别名: YP-348；(2S)-Methyl 5-allyl-1-((S)-3-(((benzyloxy)carbonyl)amino)-2-((tert-butoxycarbonyl)amino)propanoyl)pyrrolidine-2-carboxylate；methyl (2S)-1-[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(phenylmethoxycarbonylamino)propanoyl]-5-prop-2-enylpyrrolidine-2-carboxylate
• CAS: 1296138-82-3
• 化学式: C₂₅H₃₅N₃O₇
• 分子量: 489.569
• InChiKey: PMIHOMILNBFLDE-YPJRHXLCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-5-烯丙基-1-((s)-3-(((苄氧基)羰基)氨基)-2-((叔丁氧基羰基)氨基)丙酰基)吡咯烷-2-羧酸甲酯 在 palladium 10% on activated carbon 盐酸 、 氢气 、 碳酸氢钠 、 1-羟基苯并三唑 、 臭氧 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 异丙醇 为溶剂， 反应 10.0h， 生成 benzyl (5S,8S,10aR)-5-[[(2S)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoyl]amino]-6-oxo-8-(4-phenyl-1H-benzimidazol-2-yl)-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-3-carboxylate
  参考文献：
  名称：

  [EN] BIVALENT DIAZO BICYCLIC SMAC MIMETICS AND THE USES THEREOF
  [FR] MIMÉTIQUES DE SMAC BICYCLIQUES DIAZO BIVALENTS ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2011050068A3
• 作为产物：
  描述：

  (2S)-5-烯丙基-1,2-吡咯烷二羧酸 1-叔丁酯 2-甲酯 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 生成 (2S)-5-烯丙基-1-((s)-3-(((苄氧基)羰基)氨基)-2-((叔丁氧基羰基)氨基)丙酰基)吡咯烷-2-羧酸甲酯
  参考文献：
  名称：

  Debio-1143. Inhibitor of apoptosis protein (IAP) antagonist, Cancer therapy

  摘要：

  Inhibitors of apoptosis proteins (IAPs) block caspases, modulate nuclear factor NF-kappa B signaling pathways and are involved in resistance to cancer therapies. Debio-1143, a mimetic of an endogenous IAP inhibitor (second mitochondria-derived activator of caspases [SMAC]), may help to overcome treatment resistance and has demonstrated antitumor activity in various cancer cell lines and xenograft models, alone or in combination with chemotherapy, radiotherapy or immunotherapies. So far, about 150 cancer patients have been enrolled in 5 registered early-phase clinical trials testing Debio-1143. Tolerability was acceptable even when the drug was used in combination therapies. In monotherapy, pharmacokinetics was linear, but varied considerably among patients in combination settings. High tumor penetration and on-target activity were consistently shown in patient surrogate tissues and tumor biopsies. Tumor responses to second-(or higher) line monotherapy in patients with various advanced cancers were rather weak, but currently followed approaches as an adjunct to existing cancer therapies look[GRAPHICS]encouraging. Still, to identify ideal target populations and concomitant regimens remains challenging.

  DOI：

  10.1358/dof.2017.042.12.2702829

文献信息

• DIAZO BICYCLIC SMAC MIMETICS AND THE USES THEREOF
  申请人：Wang Shaomeng

  公开号：US20100273812A1

  公开（公告）日：2010-10-28

  The invention relates to diazo bicyclic mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.

  该发明涉及一种Smac的重氮双环模拟物，其作为细胞凋亡抑制蛋白抑制剂。该发明还涉及利用这些模拟物诱导细胞凋亡死亡以及使细胞对凋亡诱导剂敏感的用途。
• [EN] HETEROARYL-SUBSTITUTED BICYCLIC SMAC MIMETICS AND THE USES THEREOF<br/>[FR] SUBSTANCES MIMÉTIQUES DE SMAC BICYCLIQUES SUBSTITUÉES PAR HÉTÉROARYLE ET LEURS UTILISATIONS
  申请人：UNIV MICHIGAN

  公开号：WO2009126947A3

  公开（公告）日：2009-12-17
• EP2491041B1
  申请人：——

  公开号：EP2491041B1

  公开（公告）日：2017-08-09
• Bivalent SMAC mimetics and the uses thereof
  申请人：Wang Shaomeng

  公开号：US20080089896A1

  公开（公告）日：2008-04-17

  The invention relates to bivalent mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.
• BIVALENT SMAC MIMETICS AND THE USES THEREOF
  申请人：Wang Shaomeng

  公开号：US20090123480A1

  公开（公告）日：2009-05-14

  The invention relates to bivalent mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.