Boc-N-Me-Ala-Tle-Pro-OBn | 762274-65-7

• 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: Boc-N-Me-Ala-Tle-Pro-OBn
• 英文别名: benzyl ((S)-2-((S)-2-((tert-butoxycarbonyl)(methyl)amino)propanamido)-3,3-dimethylbutanoyl)-L-prolinate；1-{2-[2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3,3-dimethyl-butyryl}-pyrrolidine-2-carboxylic acid benzyl ester；(S)-benzyl 1-((S)-2-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-3,3-dimethylbutanoyl)pyrrolidine-2-carboxylate；Boc-N(Me)Ala-Gly(tBu)-Pro-OBn；benzyl (2S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoyl]amino]butanoyl]pyrrolidine-2-carboxylate
• CAS: 762274-65-7
• 化学式: C₂₇H₄₁N₃O₆
• 分子量: 503.639
• InChiKey: BBXPARODTSIERT-SESVDKBCSA-N

物化性质

• 沸点：
  648.7±55.0 °C(Predicted)
• 密度：
  1.140±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Boc-N-Me-Ala-Tle-Pro-OBn 在 palladium 10% on activated carbon 氢气 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 (S)-1-((S)-3,3-dimethyl-2-((S)-2-(methylamino)propanamido)butanoyl)-N-(7-methoxy-4-(methylamino)quinazolin-6-yl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  [EN] QUINOLINE OR QUINAZOLINE DERIVATIVES WITH APOPTOSIS INDUCING ACTIVITY ON CELLS
  [FR] DÉRIVÉS DE QUINOLINE OU DE QUINAZOLINE AYANT UNE ACTIVITÉ INDUISANT L'APOPTOSE SUR LES CELLULES

  摘要：

  公开号：

  WO2012030160A3
• 作为产物：
  描述：

  N-Boc-L-叔亮氨酸 在 盐酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.16h， 生成 Boc-N-Me-Ala-Tle-Pro-OBn
  参考文献：
  名称：

  Discovery of Potent Antagonists of the Antiapoptotic Protein XIAP for the Treatment of Cancer

  摘要：

  Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogues that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small molecule XIAP antagonists as a potential therapy for cancers that overexpress XIAP.

  DOI：

  10.1021/jm040037k

文献信息

• LIGAND-DIRECTED COVALENT MODIFICATION OF PROTEIN
  申请人：Petter Russell C.

  公开号：US20110269244A1

  公开（公告）日：2011-11-03

  The present invention relates to enzyme inhibitors. More specifically, the present invention relates to ligand-directed covalent modification of proteins; method of designing same; pharmaceutical formulation of same; and method of use.

  本发明涉及酶抑制剂。更具体地说，本发明涉及配体导向的蛋白共价修饰；相同设计方法；相同的药物配方；以及使用方法。
• Design, synthesis and biological evaluation of new bivalent quinazoline analogues as IAP antagonists
  作者：Inhwan Bae、Daejin Kim、Jaeyul Choi、Jisook Kim、Minjeong Kim、Bokyung Park、Young Hoon Kim、Young Gil Ahn、Ha Hyung Kim、Dae Kyong Kim

  DOI：10.1016/j.bmcl.2020.127676

  日期：2021.2

  We recently reported the biological evaluations of monovalent IAP antagonist 7 with good potency (MDA-MB-231, IC50 = 19 nM). In an effort to increase cellular activity and improve favorable drug-like properties, we newly designed and synthesized bivalent analogues based on quinazoline structure of 7. Optimization of cellular potency and CYP inhibition led to the identification of 27, which showed dramatic

  我们最近报道了具有良好效力的单价IAP拮抗剂7的生物学评估（MDA-MB-231，IC 50  = 19 nM）。为了提高细胞活性并改善类似药物的有利性质，我们基于7的喹唑啉结构新设计并合成了二价类似物。细胞效价和CYP抑制的优化导致27的鉴定，显示出超过100倍的急剧增加（IC 50  = 0.14 nM），并在MDA-MB-231异种移植模型中引起实质性的肿瘤消退。这些结果强烈支持27作为一种有前途的二价拮抗剂，用于开发有效的抗肿瘤方法。
• Tetrapeptide analogs
  申请人：Chao Bin

  公开号：US20100190688A1

  公开（公告）日：2010-07-29

  Compounds, compositions and methods for treatment of hyperproliferative diseases, such as cancer are provided.

  提供了用于治疗过度增殖性疾病，如癌症的化合物、组合物和方法。
• [EN] TETRAPEPTIDE ANALOGS<br/>[FR] ANALOGUES DE TETRAPEPTIDE
  申请人：IDUN PHARMACEUTICALS INC

  公开号：WO2006017295A3

  公开（公告）日：2007-07-12
• Ligand-Directed Covalent Modification of Protein
  申请人：Celgene CAR LLC

  公开号：US20170218353A1

  公开（公告）日：2017-08-03

  The present invention relates to enzyme inhibitors. More specifically, the present invention relates to ligand-directed covalent modification of proteins; method of designing same; pharmaceutical formulation of same; and method of use.