H-NMe-Ala-Lys(DNFB)-Pro-BHA

• 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: H-NMe-Ala-Lys(DNFB)-Pro-BHA
• 英文别名: Me-Ala-Lys(Dnp)-Pro-NHbenzhydryl；(2S)-N-benzhydryl-1-[(2S)-6-(2,4-dinitroanilino)-2-[[(2S)-2-(methylamino)propanoyl]amino]hexanoyl]pyrrolidine-2-carboxamide
• 化学式: C₃₄H₄₁N₇O₇
• 分子量: 659.742
• InChiKey: DANMQJBMVRDNPW-OIFPXGRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  48
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  194
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  叔丁氧羰基-脯氨酰-琥珀酰亚胺 在 N-甲基吗啉 、 N-[(6-chlorobenzotriazol-1-yl)oxy-(dimethylamino)methylene]-dimethyl-ammonium tetrafluoroborate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二甲基亚砜 为溶剂， 反应 7.34h， 生成 H-NMe-Ala-Lys(DNFB)-Pro-BHA
  参考文献：
  名称：

  Lipid-conjugated Smac analogues

  摘要：

  A small library of monovalent and bivalent Smac mimics was synthesized based on 2 types of monomers, with general structure NMeAla-Xaa-Pro-BHA (Xaa = Cys or Lys). Position 2 of the compounds was utilized to dimerize both types of monomers employing various bis-reactive linkers, as well as to modify selected compounds with lipids. The resulting library was screened in vitro against metastatic human breast cancer cell line MDA-MB-231, and the two most active compounds selected for in vivo studies. The most active lipid-conjugated analogue M11, showed in vivo activity while administered both subcutaneously and orally. Collectively, our findings suggest that lipidation may be a viable approach in the development of new Smac-based therapeutic leads. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.017

文献信息

• [EN] CONJUGATED ANTICANCER SMAC ANALOGS<br/>[FR] ANALOGUES SMAC ANTICANCÉREUX CONJUGUÉS
  申请人：UNIV CALIFORNIA

  公开号：WO2017044592A1

  公开（公告）日：2017-03-16

  Lipid-conjugated monovalent and bivalent secondary mitochondria derived activator of caspases (Smac) derivatives were synthesized and examined for in vitro and in vivo anticancer activity. Methods for treating cancer with these compounds are also disclosed.

  脂质共轭的一价和二价次级线粒体衍生的半胱氨酸蛋白酶激活剂（Smac）衍生物已被合成并用于体外和体内抗癌活性的检验。使用这些化合物治疗癌症的方法也被披露。
• Lipid-conjugated Smac analogues
  作者：Ewa D. Micewicz、Josephine A. Ratikan、Alan J. Waring、Julian P. Whitelegge、William H. McBride、Piotr Ruchala

  DOI：10.1016/j.bmcl.2015.09.017

  日期：2015.10

  A small library of monovalent and bivalent Smac mimics was synthesized based on 2 types of monomers, with general structure NMeAla-Xaa-Pro-BHA (Xaa = Cys or Lys). Position 2 of the compounds was utilized to dimerize both types of monomers employing various bis-reactive linkers, as well as to modify selected compounds with lipids. The resulting library was screened in vitro against metastatic human breast cancer cell line MDA-MB-231, and the two most active compounds selected for in vivo studies. The most active lipid-conjugated analogue M11, showed in vivo activity while administered both subcutaneously and orally. Collectively, our findings suggest that lipidation may be a viable approach in the development of new Smac-based therapeutic leads. (C) 2015 Elsevier Ltd. All rights reserved.