Methyl-2(S)-benzyloxycarbonylamino-3-acetylamino-propionate | 130106-12-6

• 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: Methyl-2(S)-benzyloxycarbonylamino-3-acetylamino-propionate
• 英文别名: methyl 2(S)-benzyloxycarbonylamino-3-acetylaminopropionate；methyl (2S)-3-acetamido-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 130106-12-6
• 化学式: C₁₄H₁₈N₂O₅
• 分子量: 294.307
• InChiKey: GWJLEXPIAFWALP-LBPRGKRZSA-N

物化性质

• 沸点：
  533.1±50.0 °C(Predicted)
• 密度：
  1.209±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Methyl-2(S)-benzyloxycarbonylamino-3-acetylamino-propionate 在 5%-palladium/activated carbon 、 氢气 、 1-羟基苯并三唑 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 5.75h， 生成
  参考文献：
  名称：

  Synthesis, activity and structure–activity relationship of noroviral protease inhibitors

  摘要：

  诺罗病毒（一种重要的人类病原体）的蛋白酶对其复制至关重要，因此是一个潜在的药物靶点。一系列基于三肽的蛋白酶抑制剂被设计、合成并测试，其中一些强效抑制剂被鉴定出来，其Ki值低至75 nM。这些抑制剂的结构-活性关系被讨论。

  DOI：

  10.1039/c3md00219e
• 作为产物：
  描述：

  3-氨基-N-Cbz-L-丙氨酸 在 盐酸 作用下， 以 水 为溶剂， 反应 1.5h， 生成 Methyl-2(S)-benzyloxycarbonylamino-3-acetylamino-propionate
  参考文献：
  名称：

  Tripeptide Aldehyde Inhibitors of Human Rhinovirus 3C Protease:  Design, Synthesis, Biological Evaluation, and Cocrystal Structure Solution of P₁ Glutamine Isosteric Replacements

  摘要：

  The investigation of tripeptide aldehydes as reversible covalent inhibitors of human rhinovirus (HRV) 3C protease (3CP) is reported. Molecular models based on the apo crystal structure of HRV-14 3CP and other trypsin-like serine proteases were constructed to approximate the binding of peptide substrates, generate transition state models of P-1-P-1' amide cleavage, and propose novel tripeptide aldehydes. Glutaminal derivatives have limitations since they exist predominantly in the cyclic hemiaminal form. Therefore, several isosteric replacements for the P-1 carboxamide side chain were designed and incorporated into the tripeptide aldehydes. These compounds were found to be potent inhibitors of purified HRV-14 3CP with K(i)s ranging from 0.005 to 0.64 mu M. Several have low micromolar antiviral activity when tested against HRV-14-infected H1-HeLa cells. The N-acetyl derivative 3 was also shown to be active against HRV serotypes 2, 16, and 89. High-resolution cocrystal structures of HRV-8 3CP, covalently bound to compounds 3, 15, and 16, were solved. These cocrystal structures were analyzed and compared with our original HRV-14 3CP-substrate and inhibitor models.

  DOI：

  10.1021/jm980071x

文献信息

• Inhibitors of farnesyl-protein transferase
  申请人：Merk & Co., Inc.

  公开号：US05872135A1

  公开（公告）日：1999-02-16

  The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit farnesyl-protein transferase. Furthermore, these CAAX analogues differ from those previously described as inhibitors of farnesyl-protein transferase in that they do not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

  本发明包括蛋白质Ras的CAAX基序的类似物，该基序在体内通过法尼酰化进行修饰。这些CAAX类似物抑制法尼酰蛋白转移酶。此外，这些CAAX类似物与先前描述的抑制法尼酰蛋白转移酶的类似物不同，因为它们不具有硫醇基团。缺乏硫醇基团在改善动物的药代动力学行为、预防依赖硫醇的化学反应（如快速自氧化和与内源硫醇形成二硫键）以及减少全身毒性方面提供了独特优势。本发明还包括含有这些法尼酰转移酶抑制剂的化疗组合物以及其生产方法。
• INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：Merck & Co., Inc.

  公开号：EP0783518A1

  公开（公告）日：1997-07-16
• EP0837875A4
  申请人：——

  公开号：EP0837875A4

  公开（公告）日：1998-10-07
• US5627202A
  申请人：——

  公开号：US5627202A

  公开（公告）日：1997-05-06
• US5661161A
  申请人：——

  公开号：US5661161A

  公开（公告）日：1997-08-26