BOC-(R)-3-氨基-4-(3,4-二氯苯基)丁酸 | 269396-56-7

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - BOC-氨基酸
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: BOC-(R)-3-氨基-4-(3,4-二氯苯基)丁酸
• 中文别名: (R)-3-(Boc-氨基)-4-(3,4-二氯苯基)丁酸；BOC-D-3-氨基-4-(3,4-二氯苯基)-丁酸；Boc-(R)-3-氨基-4-(3,4-二氯苯基)丁酸；(3R)-3-[(叔丁氧羰基)氨基]-4-(3,4-二氯苯基)丁酸
• 英文名称: (3R)-3-(tert-butoxycarbonylamino)-4-(3,4-dichlorophenyl)butanoic acid
• 英文别名: (R)-3-((tert-Butoxycarbonyl)amino)-4-(3,4-dichlorophenyl)butanoic acid；(3R)-4-(3,4-dichlorophenyl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid
• CAS: 269396-56-7
• 化学式: C₁₅H₁₉Cl₂NO₄
• mdl: MFCD01860949
• 分子量: 348.226
• InChiKey: WJEUUKADFJNOHW-SNVBAGLBSA-N

物化性质

• 沸点：
  494.8±45.0 °C(Predicted)
• 密度：
  1.294

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.466
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2924299090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  BOC-(R)-3-氨基-4-(3,4-二氯苯基)丁酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 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 37.0h， 生成 (3R)-3-(2-(3-amino-2-oxo-2,3,4,5-tetrahydrobenzo[b]azepin-1-yl)acetamido)-4-(3,4-dichlorophenyl)-N-methylbutanamide
  参考文献：
  名称：

  Structure Based Design of Non-Natural Peptidic Macrocyclic Mcl-1 Inhibitors

  摘要：

  Mcl-1 is a pro-apoptotic BH3 protein family member similar to Bcl-2 and Bcl-xL. Overexpression of Mcl-1 is often seen in various tumors and allows cancer cells to evade apoptosis. Here we report the discovery and optimization of a series of non-natural peptide Mcl-1 inhibitors. Screening of DNA-encoded libraries resulted in hit compound 1, a 1.5 mu M Mcl-1 inhibitor. A subsequent crystal structure demonstrated that compound 1 bound to Mcl-1 in a beta-turn conformation, such that the two ends of the peptide were close together. This proximity allowed for the linking of the two ends of the peptide to form a macrocycle. Macrocyclization resulted in an approximately 10-fold improvement in binding potency. Further exploration of a key hydrophobic interaction with Mcl-1 protein and also with the moiety that engages Arg256 led to additional potency improvements. The use of protein-ligand crystal structures and binding kinetics contributed to the design and understanding of the potency gains. Optimized compound 26 is a <3 nM Mcl-1 inhibitor, while inhibiting Bcl-2;at only 5 mu M and Bcl-xL at >99 mu M, and induces cleaved caspase-3 in MV4-11 cells with an IC50 of 3 mu M after 6 h.

  DOI：

  10.1021/acsmedchemlett.6b00464
• 作为产物：
  描述：

  N-叔丁氧羰基-D-3,4-二氯苯丙氨酸 在 silver benzoate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 为溶剂， 反应 6.0h， 生成 BOC-(R)-3-氨基-4-(3,4-二氯苯基)丁酸
  参考文献：
  名称：

  发现有效的和选择性的基于β-高苯丙氨酸的二肽基肽酶IV抑制剂。

  摘要：

  内部筛选铅β-氨基酰基脯氨酸8的修饰得到了等价的噻唑烷化物9。对9的苯环的广泛SAR研究导致发现了一系列新的有效的和选择性的DP-IV抑制剂。事实证明，在2位上引入氟对于该系列的效能至关重要。2,5-二氟（22q）和2,4,5-三氟（22t）类似物是DP-IV的有效抑制剂（分别为IC（50）= 270、119nM）。

  DOI：

  10.1016/j.bmcl.2004.06.099

文献信息

• Design, synthesis and biological evaluation of 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors
  作者：Xun Ji、Chunmei Xia、Jiang Wang、Mingbo Su、Lei Zhang、Tiancheng Dong、Zeng Li、Xia Wan、Jingya Li、Jia Li、Linxiang Zhao、Zhaobing Gao、Hualiang Jiang、Hong Liu

  DOI：10.1016/j.ejmech.2014.08.059

  日期：2014.10

  Based on the previous work in our group and the principle of computer-aided drug design, a series of novel beta-amino pyrrole-2-carbonitrile derivatives was designed and synthesized. Compounds 81 and 91 were efficacious and selective DPP4 inhibitors resulting in decreased blood glucose in vivo. Compound 81 had moderate DPP4 inhibitory activity (IC50 = 0.05 mu M) and good oral bioavailability (F = 53.2%). Compound 91 showed excellent DPP4 inhibitory activity (IC50 = 0.01 mu M), good selectivity (selective ratio: DPP8/DPP4 = 898.00; DPP9/DPP4 = 566.00) against related peptidases, and good efficacy in an oral glucose tolerance tests in ICR mice and moderate PR profiles (F = 22.8%, t(1/2) = 2.74 h). Moreover, compound 91 did not block hERG channel and exhibited no inhibition of liver metabolic enzymes such as CYP2C9. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Rodent selectivity of piperidine-4-yl-1H-indoles, a series of CC chemokine receptor-3 (CCR3) antagonists: Insights from a receptor model
  作者：Jan M. Kriegl、Domnic Martyres、Marc A. Grundl、Ralf Anderskewitz、Horst Dollinger、Georg Rast、Bernhard Schmid、Peter Seither、Christofer S. Tautermann

  DOI：10.1016/j.bmcl.2014.11.063

  日期：2015.1

  Rodent selectivity data of piperidine-4-yl-1H-indoles, a series of CC chemokine receptor-3 (CCR3) antagonists, are presented and discussed as part of an overall optimization effort within this lead compound class. Although attachment of an acidic moiety to the 1-position of the indole led to an overall balanced in vitro profile, in particular reducing inhibition of the hERG channel, potency on the rat and mouse receptor worsened. These findings could be rationalized in the context of a CCR3 homology model. (C) 2014 Elsevier Ltd. All rights reserved.
• US8138168B1
  申请人：——

  公开号：US8138168B1

  公开（公告）日：2012-03-20