tert-butyl ((S)-1-(((3S,6S,7R,9aS)-7-(2-aminoethyl)-3-(benzhydrylcarbamoyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepin-6-yl)amino)-1-oxobutan-2-yl)(methyl)carbamate | 1190769-24-4

• 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: tert-butyl ((S)-1-(((3S,6S,7R,9aS)-7-(2-aminoethyl)-3-(benzhydrylcarbamoyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepin-6-yl)amino)-1-oxobutan-2-yl)(methyl)carbamate
• CAS: 1190769-24-4
• 化学式: C₃₅H₄₉N₅O₅
• 分子量: 619.805
• InChiKey: QVEMOOJEHPAIMR-QUBFWBSFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.14
• 重原子数：
  45.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  134.07
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  tert-butyl ((S)-1-(((3S,6S,7R,9aS)-7-(2-aminoethyl)-3-(benzhydrylcarbamoyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepin-6-yl)amino)-1-oxobutan-2-yl)(methyl)carbamate 在 盐酸 、 甲醇 、 sodium tetrahydroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.17h， 生成 (3s,6s,7r,9as)-7-[2-(Benzylamino)ethyl]-N-(Diphenylmethyl)-6-{[(2s)-2-(Methylamino)butanoyl]amino}-5-Oxooctahydro-1h-Pyrrolo[1,2-A]azepine-3-Carboxamide
  参考文献：
  名称：

  Rational design, synthesis and characterization of potent, drug-like monomeric Smac mimetics as pro-apoptotic anticancer agents

  摘要：

  A set of phenyl-substituted Smac mimetics/IAP inhibitor analogues of lead compound 2a was synthesized, aiming to retain its strong cell-free potency while increasing its bioavailability. Seventeen compounds 2b-r were prepared and characterized in vitro, using cell-free and cellular assays. Among them, the p-CF3 substituted analogue 2m showed the best permeability through cell membranes, and was selected for further in vitro and in vivo studies due to its strong, sub-micromolar cellular potency. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.098
• 作为产物：
  描述：

  (3aS,5R,7aS,9aS)-3-benzyl-4-oxo-decahydro-2-oxa-3,4a-diazacyclopenta[f]azulene-5-carboxylic acid tert-butyl ester 在 三乙基硅烷 、 甲烷磺酸 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 palladium on activated charcoal 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 柠檬酸 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 85.0 ℃ 、6.0 MPa 条件下， 反应 66.34h， 生成 tert-butyl ((S)-1-(((3S,6S,7R,9aS)-7-(2-aminoethyl)-3-(benzhydrylcarbamoyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepin-6-yl)amino)-1-oxobutan-2-yl)(methyl)carbamate
  参考文献：
  名称：

  Rational design, synthesis and characterization of potent, drug-like monomeric Smac mimetics as pro-apoptotic anticancer agents

  摘要：

  A set of phenyl-substituted Smac mimetics/IAP inhibitor analogues of lead compound 2a was synthesized, aiming to retain its strong cell-free potency while increasing its bioavailability. Seventeen compounds 2b-r were prepared and characterized in vitro, using cell-free and cellular assays. Among them, the p-CF3 substituted analogue 2m showed the best permeability through cell membranes, and was selected for further in vitro and in vivo studies due to its strong, sub-micromolar cellular potency. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.098

文献信息

• Synthesis and biological evaluation of dual action <i>cyclo</i>-RGD/SMAC mimetic conjugates targeting α_vβ₃/α_vβ₅ integrins and IAP proteins
  作者：M. Mingozzi、L. Manzoni、D. Arosio、A. Dal Corso、M. Manzotti、F. Innamorati、L. Pignataro、D. Lecis、D. Delia、P. Seneci、C. Gennari

  DOI：10.1039/c4ob00207e

  日期：——

  The rational design, synthesis and in vitro biological evaluation of dual action conjugates 11–13, containing a tumour targeting, integrin αvβ3/αvβ5 ligand portion and a pro-apoptotic SMAC mimetic portion (cyclo-RGD/SMAC mimetic conjugates) are reported. The binding strength of the two separate units is generally maintained by these dual action conjugates. In particular, the connection between the

  合理的设计，合成和体外双重作用缀合物的生物学评价11-13，含有肿瘤靶向，整合素α v β 3 /α v β 5的配体部分和促凋亡SMAC模拟物部分（环-RGD / SMAC模拟物共轭）。通常通过这些双重作用缀合物来维持两个分开的单元的结合强度。特别地，单独的单元（锚点每个单元上;性质，长度和接头的稳定性）之间的连接影响针对其分子靶的每个部分的活性（整合α v β 3 /α v β对于环-RGD为5，对于SMAC模拟物为IAP蛋白）。每个缀合物部分耐受不同的取代，同时保留对每个靶标的结合亲和力。
• Rational design, synthesis and characterization of potent, non-peptidic Smac mimics/XIAP inhibitors as proapoptotic agents for cancer therapy
  作者：Pierfausto Seneci、Aldo Bianchi、Cristina Battaglia、Laura Belvisi、Martino Bolognesi、Andrea Caprini、Federica Cossu、Elena de Franco、Marilenia de Matteo、Domenico Delia、Carmelo Drago、Amira Khaled、Daniele Lecis、Leonardo Manzoni、Moira Marizzoni、Eloise Mastrangelo、Mario Milani、Ilaria Motto、Elisabetta Moroni、Donatella Potenza、Vincenzo Rizzo、Federica Servida、Elisa Turlizzi、Maurizio Varrone、Francesca Vasile、Carlo Scolastico

  DOI：10.1016/j.bmc.2009.07.009

  日期：2009.8

  Novel proapoptotic Smac mimics/IAPs inhibitors have been designed, synthesized and characterized. Computational models and structural studies (crystallography, NMR) have elucidated the SAR of this class of inhibitors, and have permitted further optimization of their properties. In vitro characterization (XIAP BIR3 and linker-BIR2-BIR3 binding, cytotox assays, early ADMET profiling) of the compounds has been performed, identifying one lead for further in vitro and in vivo evaluation. (C) 2009 Elsevier Ltd. All rights reserved.