(S,5S,5′S,8S,8′S,10aR,10a′R)-N3,N3′-(octane-1,8-diyl)bis(N8-benzhydryl-5-((S)-2-(methylamino)propanamido)-6-oxooctahydropyrrolo[1,2-a][1,5]diazocine-3,8(4H)-dicarboxamide) | 1432724-89-4

• 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,5S,5′S,8S,8′S,10aR,10a′R)-N3,N3′-(octane-1,8-diyl)bis(N8-benzhydryl-5-((S)-2-(methylamino)propanamido)-6-oxooctahydropyrrolo[1,2-a][1,5]diazocine-3,8(4H)-dicarboxamide)
• 英文别名: (5S,8S,10aR)-3-N-[8-[[(5S,8S,10aR)-8-(benzhydrylcarbamoyl)-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-3-carbonyl]amino]octyl]-8-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-3,8-dicarboxamide
• CAS: 1432724-89-4
• 化学式: C₆₄H₈₆N₁₂O₈
• 分子量: 1151.46
• InChiKey: HLFSVLWTUQVBNO-YBEGZINPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  84
• 可旋转键数：
  23
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  246
• 氢给体数：
  8
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 生成 (S,5S,5′S,8S,8′S,10aR,10a′R)-N3,N3′-(octane-1,8-diyl)bis(N8-benzhydryl-5-((S)-2-(methylamino)propanamido)-6-oxooctahydropyrrolo[1,2-a][1,5]diazocine-3,8(4H)-dicarboxamide)
  参考文献：
  名称：

  A Potent Bivalent Smac Mimetic (SM-1200) Achieving Rapid, Complete, and Durable Tumor Regression in Mice

  摘要：

  We have designed, synthesized, and evaluated a series of new compounds based upon our previously reported bivalent Smac mimetics. This led to the identification of compound 12 (SM-1200), which binds to XIAP, cIAP1, and cIAP2 with K-i values of 0.5, 3.7, and 5.4 nM, respectively, inhibits cell growth in the MDA-MB-231 breast cancer and SK-OV-3 ovarian cancer cell lines with IC50 values of 11.0 and 28.2 nM, respectively. Compound 12 has a much improved pharmacokinetic profile over our previously reported bivalent Smac mimetics and is highly effective in induction of rapid and durable tumor regression in the MDA-MB-231 xenograft model. These data indicate that compound 12 is a promising Smac mimetic and warrants extensive evaluation as a potential candidate for clinical development.

  DOI：

  10.1021/jm400216d

文献信息

• BIVALENT INHIBITORS OF IAP PROTEINS AND THERAPEUTIC METHODS USING THE SAME
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US20140057924A1

  公开（公告）日：2014-02-27

  Inhibitors of IAP proteins and compositions containing the same are disclosed. Methods of using the IAP protein inhibitors in the treatment of diseases and conditions wherein inhibition of IAP proteins provides a benefit, like cancers, also are disclosed.

  抑制IAP蛋白质的抑制剂和含有这些抑制剂的组合物被披露。还披露了使用IAP蛋白质抑制剂治疗疾病和状况的方法，其中抑制IAP蛋白质提供益处，如癌症等。
• A Potent Bivalent Smac Mimetic (SM-1200) Achieving Rapid, Complete, and Durable Tumor Regression in Mice
  作者：Rong Sheng、Haiying Sun、Liu Liu、Jianfeng Lu、Donna McEachern、Guanfeng Wang、Jianfeng Wen、Ping Min、Zhenyun Du、Huirong Lu、Sanmao Kang、Ming Guo、Dajun Yang、Shaomeng Wang

  DOI：10.1021/jm400216d

  日期：2013.5.23

  We have designed, synthesized, and evaluated a series of new compounds based upon our previously reported bivalent Smac mimetics. This led to the identification of compound 12 (SM-1200), which binds to XIAP, cIAP1, and cIAP2 with K-i values of 0.5, 3.7, and 5.4 nM, respectively, inhibits cell growth in the MDA-MB-231 breast cancer and SK-OV-3 ovarian cancer cell lines with IC50 values of 11.0 and 28.2 nM, respectively. Compound 12 has a much improved pharmacokinetic profile over our previously reported bivalent Smac mimetics and is highly effective in induction of rapid and durable tumor regression in the MDA-MB-231 xenograft model. These data indicate that compound 12 is a promising Smac mimetic and warrants extensive evaluation as a potential candidate for clinical development.