BOC-(R)-3-氨基-4-(3-氯苯基)-丁酸 | 331763-56-5

• 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-氯苯基)-丁酸
• 中文别名: N-叔丁氧羰基-(R)-3-氨基-4-(3-氯苯基)丁酸；(βr)-3-氯-β-[[(1,1-二甲基乙氧基)羰基]氨基]-苯丁酸；BOC-D-3-氨基-4-(3-氯苯基)-丁酸
• 英文名称: (3R)-3-[[(tert-butoxy)carbonyl]amino]-4-(3-chlorophenyl)butanoic acid
• 英文别名: Boc-(R)-3-amino-4-(3-chloro-phenyl)-butyric acid；(R)-3-(tert-butoxycarbonylamino)-4-(3-chlorophenyl)butanoic acid；(R)-3-((tert-Butoxycarbonyl)amino)-4-(3-chlorophenyl)butanoic acid；(3R)-4-(3-chlorophenyl)-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid
• CAS: 331763-56-5
• 化学式: C₁₅H₂₀ClNO₄
• 分子量: 313.781
• InChiKey: APXVJJBVNYZEDD-GFCCVEGCSA-N

物化性质

• 沸点：
  470.0±40.0 °C(Predicted)
• 密度：
  1.220

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 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：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  BOC-(R)-3-氨基-4-(3-氯苯基)-丁酸 在 三乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.75h， 生成 (3R)-3-[2-[(3S)-3-[(3S)-3-amino-4-(4-chlorophenyl)butanamido]-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]acetamido]-4-(3-chlorophenyl)-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

文献信息

• Discovery of β-homophenylalanine based pyrrolidin-2-ylmethyl amides and sulfonamides as highly potent and selective inhibitors of dipeptidyl peptidase IV
  作者：Sonja Nordhoff、Silvia Cerezo-Gálvez、Holger Deppe、Oliver Hill、Meritxell López-Canet、Christian Rummey、Meinolf Thiemann、Victor G. Matassa、Paul J. Edwards、Achim Feurer

  DOI：10.1016/j.bmcl.2009.05.109

  日期：2009.8

  Modifications of DPP-4 inhibitor 5, that was discovered by structure based design, are described and structure–activity relationships discussed. With analogue 7k one of the most potent non-covalent inhibitors of DPP-4 reported to date (IC50 = 0.38 nM) was discovered. X-ray structure of inhibitor 7k bound to DPP-4 revealed a hydrogen bonding interaction with Q553. First successful efforts in balancing

  描述了通过基于结构的设计发现的DPP-4抑制剂5的修饰，并讨论了结构与活性之间的关系。使用类似物7k，发现了迄今为止报道的最有效的DPP-4非共价抑制剂之一（IC 50  = 0.38 nM）。与DPP-4结合的抑制剂7k的X射线结构揭示了与Q553的氢键相互作用。通过改善新陈代谢的稳定性证明，在平衡整体特性方面的首次成功尝试凸显了该系列产品的潜力。
• INHIBITORS OF FATTY ACID BINDING PROTEIN
  申请人：CHENG CLIFFORD

  公开号：US20120122837A1

  公开（公告）日：2012-05-17

  The present invention relates to novel heterocyclic compounds as Fatty Acid Binding Protein (“FABP”) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose.

  本发明涉及一种新颖的杂环化合物，作为脂肪酸结合蛋白（“FABP”）抑制剂，包括含有这些杂环化合物的药物组合物，并且利用这些化合物用于治疗或预防心血管疾病、代谢紊乱、肥胖或与肥胖相关的疾病、糖尿病、血脂异常、糖尿病并发症、糖耐量受损或空腹血糖受损。
• DPP-IV inhibitors
  申请人：Santhera Pharmaceuticals (Deutschland) Aktiengesellschaft

  公开号：EP1604989A8

  公开（公告）日：2006-03-15

  The invention relates to compounds of formula (I) wherein Z, R1-9, n, A, X and Rb have the meaning as cited in the description and the claims. Said compounds are useful as DPP-IV inhibitors. The invention also relates to the preparation of such compounds as well as the production and use thereof as medicament.

  该发明涉及式（I）中的化合物，其中Z、R1-9、n、A、X和Rb的含义如描述和权利要求中所述。所述化合物可用作DPP-IV抑制剂。该发明还涉及制备这种化合物以及其作为药物的生产和使用。
• Dpp-IV Inhibitors
  申请人：Edwards John Paul

  公开号：US20080015146A1

  公开（公告）日：2008-01-17

  The invention relates to compounds of formula (I) wherein Z, R 1-9 , n, A, X and R b have the meaning as cited in the description and the claims. Said compounds are useful as DPP-IV inhibitors. The invention also relates to the preparation of such compounds as well as the production and use thereof as medicament.

  本发明涉及公式(I)的化合物，其中Z、R1-9、n、A、X和Rb的含义如所述描述和权利要求中所述。所述化合物可用作DPP-IV抑制剂。本发明还涉及制备这些化合物的方法，以及作为药物的生产和使用。
• Dpp-Iv Inhibitors
  申请人：Edwards Paul John

  公开号：US20080027035A1

  公开（公告）日：2008-01-31

  The invention relates to compounds of formula (I) wherein Z, R 1-5 , X, n, A 1 and A 2 have the meaning as cited in the description and the claims. Said compounds are useful as DPP-IV inhibitors. The invention also relates to the preparation of such compounds as well as the production and use thereof as medicament.

  本发明涉及式（I）的化合物，其中Z，R1-5，X，n，A1和A2的含义如所述及权利要求中所述。所述化合物可用作DPP-IV抑制剂。本发明还涉及制备这种化合物以及其作为药物的生产和使用。