ethyl 4-((tert-butoxycarbonyl)amino)-4-methylpentanoate | 1198225-82-9

• 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: ethyl 4-((tert-butoxycarbonyl)amino)-4-methylpentanoate
• 英文别名: Boc-Aic-OEt；N-Boc-4-aminoisocaproic ethyl ester；ethyl 4-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate
• CAS: 1198225-82-9
• 化学式: C₁₃H₂₅NO₄
• 分子量: 259.346
• InChiKey: UWKFNECEGBXXDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-((tert-butoxycarbonyl)amino)-4-methylpentanoate 在 锂硼氢 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以41%的产率得到tert-butyl 5-hydroxy-2,2-dimethylpyrrolidine-1-carboxylate
  参考文献：
  名称：

  Discovery of Highly Potent Human Deoxyuridine Triphosphatase Inhibitors Based on the Conformation Restriction Strategy

  摘要：

  Human deoxyuridine triphosphatase (dUTPase) inhibition is a promising approach to enhance the efficacy of thymidylate synthase (TS) inhibitor based chemotherapy. In this study, we describe the discovery of a novel class of human dUTPase inhibitors based on the conformation restriction strategy. On the basis of the X-ray cocrystal structure of dUTPase and its inhibitor compound 7, we designed and synthesized two conformation restricted analogues, i.e., compounds 8 and 9. These compounds exhibited increased in vitro potency compared with the parent compound 7. Further structure activity relationship (SAR) studies identified a compound 43 with the highest in vitro potency (IC50 = 39 nM, EC50 = 66 nM). Furthermore, compound 43 had a favorable oral PK profile and exhibited potent antitumor activity in combination with 5-fluorouracil (5-FU) in the MX-1 breast cancer xenograft model. These results suggested that a dUTPase inhibitor may have potential for clinical usage.

  DOI：

  10.1021/jm300416h
• 作为产物：
  描述：

  1-羟基-2-甲基丙烷-2-氨基甲酸叔丁酯 在 吡啶 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二甲基亚砜 、 乙酸乙酯 、 甲苯 、 mineral oil 为溶剂， 反应 6.5h， 生成 ethyl 4-((tert-butoxycarbonyl)amino)-4-methylpentanoate
  参考文献：
  名称：

  Discovery of Highly Potent Human Deoxyuridine Triphosphatase Inhibitors Based on the Conformation Restriction Strategy

  摘要：

  Human deoxyuridine triphosphatase (dUTPase) inhibition is a promising approach to enhance the efficacy of thymidylate synthase (TS) inhibitor based chemotherapy. In this study, we describe the discovery of a novel class of human dUTPase inhibitors based on the conformation restriction strategy. On the basis of the X-ray cocrystal structure of dUTPase and its inhibitor compound 7, we designed and synthesized two conformation restricted analogues, i.e., compounds 8 and 9. These compounds exhibited increased in vitro potency compared with the parent compound 7. Further structure activity relationship (SAR) studies identified a compound 43 with the highest in vitro potency (IC50 = 39 nM, EC50 = 66 nM). Furthermore, compound 43 had a favorable oral PK profile and exhibited potent antitumor activity in combination with 5-fluorouracil (5-FU) in the MX-1 breast cancer xenograft model. These results suggested that a dUTPase inhibitor may have potential for clinical usage.

  DOI：

  10.1021/jm300416h

文献信息

• Remarkable thermoresponsive nanofibers from γ-peptides
  作者：Sandip V. Jadhav、Hosahudya N. Gopi

  DOI：10.1039/c3cc45383a

  日期：——

  Conformational analysis of γ-peptides composed of 4,4-gem-dimethyl γ-amino acids, their spontaneous self-assembly into nanofibrillar superstructures and remarkable thermoreversible gelation properties in various organic solvents are studied. This new generation of γ-peptides may serve as potential templates to design advanced biomaterials.

  研究了由 4,4-gem-dimethyl δ³-amino acids 组成的 δ³ 肽的构象分析、它们在各种有机溶剂中自发自组装成纳米纤维超结构和显著的热可逆凝胶特性。这种新一代δ-肽可作为设计先进生物材料的潜在模板。
• Structural Dimorphism of Achiral α,γ‐Hybrid Peptide Foldamers: Coexistence of 12‐ and 15/17‐Helices
  作者：Rajkumar Misra、Abhijith Saseendran、Gijo George、Kuruva Veeresh、K. Muruga Poopathi Raja、Srinivasarao Raghothama、Hans‐Jörg Hofmann、Hosahudya N. Gopi

  DOI：10.1002/chem.201605753

  日期：2017.3.13

  of continuously lengthened Aib/Aic‐hybrid peptides confirm that the 12‐helix is more stable than the 15/17‐helix in shorter peptides, whereas the 15/17‐helix is more stable in longer sequences. Thus, the coexistence of both helix types can be expected within a definite range of sequence lengths. The novel 15/17‐ and 12‐helices in α,γ‐hybrid peptides with 5→1 and 4→1 hydrogen‐bonding patterns, respectively

  在这里，报道了由非手性α-氨基异丁酸（Aib）和4-氨基异己酸（Aic，双重同源的Aib）单体以1：1交替组成的α，γ-杂合肽中的新型12螺旋。通过对四肽和七肽的溶液和晶体结构分析表明了12个螺旋。出乎意料的是，更长的九肽单晶显示出两种不同的螺旋类型：新颖的12螺旋和前所未有的15/17螺旋。一系列连续加长的Aib / Aic杂合肽中两种螺旋类型的量子化学计算证实，短肽中12螺旋比15/17螺旋更稳定，而15/17螺旋在短肽中更稳定较长的序列。因此，可以在一定的序列长度范围内预期两种螺旋类型的共存。α中的新颖15/17和12螺旋10个螺旋。