(s)-4-(cbz-氨基)-5-甲基-3-氧代己酸叔丁酯 | 191731-16-5

• 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: (s)-4-(cbz-氨基)-5-甲基-3-氧代己酸叔丁酯
• 中文别名: (S)-4-(CBZ-氨基)-3-氧代-5-甲基己酸叔丁酯；(S)-4-(Cbz-氨基)-3-氧代-5-甲基己酸叔丁酯
• 英文名称: (S)-tert-butyl 4-(benzyloxycarbonyl)amino-5-methyl-3-oxohexanoate
• 英文别名: t-butyl-(4S)-4-(N-benzyloxycarbonylamino)-5-methyl-3-oxohexanoate；Tert-butyl (S)-4-(cbz-amino)-5-methyl-3-oxohexanoate；tert-butyl (4S)-5-methyl-3-oxo-4-(phenylmethoxycarbonylamino)hexanoate
• CAS: 191731-16-5
• 化学式: C₁₉H₂₇NO₅
• 分子量: 349.427
• InChiKey: FGKFTCDIARXOCS-KRWDZBQOSA-N

物化性质

• 沸点：
  464.4±35.0 °C(Predicted)
• 密度：
  1.100±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  (s)-4-(cbz-氨基)-5-甲基-3-氧代己酸叔丁酯 在 palladium on activated charcoal 吗啉 、 N-甲基吗啉 、 盐酸 、 四(三苯基膦)钯 、 氢气 、 sodium hydride 、 caesium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 70.0h， 生成 (2R,5S)-5-(2,2-Dimethyl-propionylamino)-2-isobutyl-6-methyl-4-oxo-heptanoic acid
  参考文献：
  名称：

  Discovery of Potent Anilide Inhibitors against the Severe Acute Respiratory Syndrome 3CL Protease

  摘要：

  A diversified library of peptide anilides was prepared, and their inhibition activities against the SARS-CoV 3CL protease were examined by a fluorogenic tetradecapeptide substrate. The most potent inhibitor is an anilide derived from 2-chloro-4-nitroaniline, L-phenylalanine and 4-(dimethylamino)benzoic acid. This anilide is a competitive inhibitor of the SARS-CoV 3CL protease with K-i = 0.03 mu M. The molecular docking experiment indicates that the P1 residue of this anilide inhibitor is distant from the nucleophilic SH of Cys145 in the active site.

  DOI：

  10.1021/jm050184y
• 作为产物：
  描述：

  醋酸叔丁酯 、 甲基N-[(苄氧基)羰基]-L-缬氨酸酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 乙基苯 为溶剂， 以89%的产率得到(s)-4-(cbz-氨基)-5-甲基-3-氧代己酸叔丁酯
  参考文献：
  名称：

  An efficient synthesis of γ-amino β-ketoester by cross-Claisen condensation with α-amino acid derivatives

  摘要：

  Cross-ester condensation between N-protected amino acid ester and the lithium enolate prepared from alkyl acetate gave the corresponding beta-ketoester in high yield without the formation of the tertiary alcohol that is commonly seen as by-product. This interesting reaction is applicable to the amino acid derivatives with suitable N-protecting groups, which can help to stabilize the reaction intermediates. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(03)00464-7

文献信息

• Improved synthesis of rupintrivir
  作者：DaiZong Lin、WangKe Qian、Rolf Hilgenfeld、HuaLiang Jiang、KaiXian Chen、Hong Liu

  DOI：10.1007/s11426-011-4478-5

  日期：2012.6

  An improved synthesis of rupintrivir (AG7088) was accomplished using three amino acids (l-glutamic acid, d-4-fluorophenylalanine, and l-valine) as the building blocks. The key fragment ketomethylene dipeptide isostere was constructed with the valine derivative and phenylpropionic acid derivative, followed by coupling with a lactam derivative and an isoxazole acid chloride to provide AG7088 totally in eight steps.

  对rupintrivir (AG7088) 的改进合成使用了三种氨基酸（l-谷氨酸、d-4-氟苯丙氨酸和l-缬氨酸）作为构建块。关键片段酮亚甲基二肽异构体通过缬氨酸衍生物和苯丙酸衍生物的构建而成，随后与内酰胺衍生物和异恶唑酸氯化物偶联，最终在八个步骤中合成出AG7088。
• A simple, stereoselective synthesis of ketomethylene dipeptide isosteres
  作者：Robert V. Hoffman、Junhua Tao

  DOI：10.1016/s0040-4020(97)00410-9

  日期：1997.5

  An exceedingly simple, general, and stereoselective method for the preparation of ketomethylene dipeptide isosteres (5-(carbobenzyloxyamino)-2-alkyl-γ-ketoesters) from Cbz-protected amino acids and scalemic 2-triflyloxy esters has been developed. The method is short (three steps), efficient, and highly diastereoselective and enantioselective.

  已经开发了一种非常简单，通用和立体选择性的方法，该方法可从Cbz保护的氨基酸和规模的2-triflyloxy酯制备酮亚甲基二肽等位异构体（5-（羰基苄氧基氨基）-2-烷基-γ-酮酸酯）。该方法是短的（三个步骤），有效的，高度非对映选择性和对映选择性的。
• Pentapeptides as antitumor agents
  申请人：Basf Aktiengesellschaft

  公开号：US05741892A1

  公开（公告）日：1998-04-21

  The present invention provides anti-tumor peptides of Formula I, A-B-N (CH.sub.3)-CHD-CH(OCH.sub.3)-CH.sub.2 CO-Pro-Pro-K (I), and the acid salts thereof. A is an amino acid residue of the formula (CH.sub.3).sub.2 N--CHX--CO, wherein X is a normal or branched alkyl group. B is an amino acid residue selected from the group consisting of valyl, isoleucyl, leucyl, and 2-t-butylglycyl. D is a normal or branched C.sub.3 -C.sub.4 -alkyl group. K is a t-butoxy group or a substituted amino group. An additional embodiment of the present invention is a method for treating a malignancy in a mammal, such as a human, comprising administering to the mammal an effective amount of a compound or compounds of Formula I in a pharmaceutically acceptable composition.

  本发明提供了化学式I，A-B-N（CH.sub.3）-CHD-CH（OCH.sub.3）-CH.sub.2 CO-Pro-Pro-K（I）及其酸盐的抗肿瘤肽。其中，A是化学式（CH.sub.3）.sub.2 N--CHX--CO的氨基酸残基，其中X是正常或支链烷基。B是从缬氨酰基、异亮氨酰基、亮氨酰基和2-叔丁基甘氨酰基组成的氨基酸残基。D是正常或支链C.sub.3-C.sub.4-烷基。K是叔丁氧基或取代氨基。本发明的另一实施例是一种治疗哺乳动物（如人类）恶性肿瘤的方法，包括向哺乳动物投与化学式I化合物或化合物的有效量，以药学上可接受的组合物形式给药。
• Tetrapeptides as antitumor agents
  申请人：BASF Aktiengesellschaft

  公开号：US05939527A1

  公开（公告）日：1999-08-17

  The present invention provides anti-tumor peptides of Formula I, A--B--NR.sup.3 --CHD--CH(OCH.sub.3)--CH.sub.2 CO--E--K (I), and the acid salts thereof. A is an amino acid residue selected from the group consisting of N-methyl-D-prolyl, N-methyl-D-homoprolyl and N,N-dimethyl-2-ethylphenylglycyl, or an amino acid residue of the formula R.sup.1 R.sup.2 N--CHX--CO, wherein R.sup.1 is a-methyl group or an ethyl group, R.sup.2 is a hydrogen atom, a methyl group or an ethyl group, and X is an alkyl group. B is an amino acid residue selected from the group consisting of valyl, isoleucyl, leucyl, and 2-t-butylglycyl. R.sup.3 is a hydrogen atom or a methyl group. D is a normal or branched C.sub.2 -C.sub.5 -alkyl group. E is an amino acid residue selected from the group consisting of prolyl, homoprolyl, 5-methylprolyl, and phenylalanyl, or E is a residue derived from an amino acid comprising a pyrrolidine group. K is an alkoxy group or an amino group. An additional embodiment of the present invention is a method for treating a malignancy in a mammal, such as a human, comprising administering to the mammal an effective amount of a compound or compounds of Formula I in a pharmaceutically acceptable composition.

  本发明提供了化学式I的抗肿瘤肽，A--B--NR.sup.3 --CHD--CH(OCH.sub.3)--CH.sub.2 CO--E--K（I）及其酸盐。其中，A是从N-甲基-D-脯氨酰、N-甲基-D-同脯氨酰和N,N-二甲基-2-乙基苯甘氨酰组成的氨基酸残基，或者是化学式R.sup.1 R.sup.2 N--CHX--CO中的氨基酸残基，其中R.sup.1是α-甲基基团或乙基基团，R.sup.2是氢原子、甲基基团或乙基基团，X是烷基基团。B是从缬氨酰、异亮氨酰、亮氨酰和2-叔丁基甘氨酰组成的氨基酸残基。R.sup.3是氢原子或甲基基团。D是正常或支链的C.sub.2 -C.sub.5烷基基团。E是从脯氨酰、同脯氨酰、5-甲基脯氨酰和苯基丙氨酰组成的氨基酸残基，或者E是由含有吡咯烷基团的氨基酸衍生的残基。K是烷氧基团或氨基团。本发明的另一实施例是一种治疗哺乳动物（如人类）恶性肿瘤的方法，包括向哺乳动物投与化学式I化合物的有效量的药物合成可接受的组合物。
• Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters
  作者：Jiun-Jie Shie、Jim-Min Fang、Tun-Hsun Kuo、Chih-Jung Kuo、Po-Huang Liang、Hung-Jyun Huang、Yin-Ta Wu、Jia-Tsrong Jan、Yih-Shyun E. Cheng、Chi-Huey Wong

  DOI：10.1016/j.bmc.2005.05.065

  日期：2005.9

  The proteolytic processing of polyproteins by the 3CL protease of severe acute respiratory syndrome coronavirus is essential for the viral propagation. A series of tripeptide alpha,beta-unsaturated esters and ketomethylene isosteres, including AG7088, are synthesized and assayed to target the 3CL protease. Though AG7088 is inactive (IC50 > 100 mu M), the ketomethylene isosteres and tripeptide alpha,beta-unsaturated esters containing both P1 and P2 phenylalanine residues show modest inhibitory activity (IC50 = 11-39 mu M). The Phe-Phe dipeptide inhibitors 18a-e are designed on the basis of computer modeling of the enzyme-inhibitor complex. The most potent inhibitor 18c with an inhibition constant of 0.52 mu M is obtained by condensation of the Phe-Phe dipeptide alpha,beta-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of 0.18 mu M. (c) 2005 Elsevier Ltd. All rights reserved.