(S)-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-7-((3R,5S)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide

• 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
• 英文名称: (S)-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-7-((3R,5S)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
• 英文别名: (3S)-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-7-[(3R,5S)-5-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]pyrrolidin-3-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
• 化学式: C₃₅H₄₀N₄O₂
• 分子量: 548.728
• InChiKey: NQZNALAIRDUZRL-KCYSLWQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  41
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  82.3
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-7-((3R,5S)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 在 N-甲基吗啉 、 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  Discovery of Potent Heterodimeric Antagonists of Inhibitor of Apoptosis Proteins (IAPs) with Sustained Antitumor Activity

  摘要：

  The prominent role of IAPs in controlling cell death and their overexpression in a variety of cancers has prompted the development of IAP antagonists as potential antitumor therapies. We describe the identification of a series of heterodimeric antagonists with highly potent antiproliferative activities in cIAP- and XIAP-dependent cell lines. Compounds 15 and 17 further demonstrate curative efficacy in human melanoma and lung cancer xenograft models and are promising candidates for advanced studies.

  DOI：

  10.1021/jm501482t
• 作为产物：
  描述：

  3,5-二碘-L-酪氨酸 在 N-甲基吗啉 、 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 N-羟基-7-氮杂苯并三氮唑 、 palladium bis[bis(diphenylphosphino)ferrocene] dichloride 、 5%-palladium/activated carbon 、 氢气 、 potassium acetate 、 碳酸氢钠 、 sodium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 95.0 ℃ 、172.37 kPa 条件下， 反应 33.75h， 生成 (S)-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-7-((3R,5S)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  Discovery of Potent Heterodimeric Antagonists of Inhibitor of Apoptosis Proteins (IAPs) with Sustained Antitumor Activity

  摘要：

  The prominent role of IAPs in controlling cell death and their overexpression in a variety of cancers has prompted the development of IAP antagonists as potential antitumor therapies. We describe the identification of a series of heterodimeric antagonists with highly potent antiproliferative activities in cIAP- and XIAP-dependent cell lines. Compounds 15 and 17 further demonstrate curative efficacy in human melanoma and lung cancer xenograft models and are promising candidates for advanced studies.

  DOI：

  10.1021/jm501482t

文献信息

• IAP antagonists
  申请人：Bristol-Myers Squibb Company

  公开号：US08889712B2

  公开（公告）日：2014-11-18

  There are disclosed compounds that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.

  本发明揭示了一些化合物，这些化合物可以调节凋亡抑制因子（IAPs）的活性，包括含有所述化合物的制药组合物以及利用本发明的化合物治疗增殖性疾病和凋亡失调性疾病，例如癌症的方法。
• IAP ANTAGONISTS
  申请人：Bristol-Myers Squibb Company

  公开号：US20130338081A1

  公开（公告）日：2013-12-19

  There are disclosed compounds that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.

  本发明揭示了一种调节细胞凋亡抑制因子（IAPs）活性的化合物，包括含有所述化合物的制药组合物以及利用该发明中的化合物治疗增殖性疾病和失调凋亡疾病，例如癌症的方法。
• 1,2,3,4-Tetrahydroisoquinoline-pyrrolidine derivatives as antagonists of apoptosis (IAPs) for the treatment of cancer.
  申请人：Bristol-Myers Squibb Company

  公开号：EP2861581B1

  公开（公告）日：2017-02-01
• US8889712B2
  申请人：——

  公开号：US8889712B2

  公开（公告）日：2014-11-18
• Discovery of Potent Heterodimeric Antagonists of Inhibitor of Apoptosis Proteins (IAPs) with Sustained Antitumor Activity
  作者：Heidi L. Perez、Charu Chaudhry、Stuart L. Emanuel、Caroline Fanslau、Joseph Fargnoli、Jinping Gan、Kyoung S. Kim、Ming Lei、Joseph G. Naglich、Sarah C. Traeger、Ragini Vuppugalla、Donna D. Wei、Gregory D. Vite、Randy L. Talbott、Robert M. Borzilleri

  DOI：10.1021/jm501482t

  日期：2015.2.12

  The prominent role of IAPs in controlling cell death and their overexpression in a variety of cancers has prompted the development of IAP antagonists as potential antitumor therapies. We describe the identification of a series of heterodimeric antagonists with highly potent antiproliferative activities in cIAP- and XIAP-dependent cell lines. Compounds 15 and 17 further demonstrate curative efficacy in human melanoma and lung cancer xenograft models and are promising candidates for advanced studies.