L-leucine-L-tryptophan benzyl ester | 152290-27-2

• 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: L-leucine-L-tryptophan benzyl ester
• 英文别名: Leu-Trp-OBzl；NH2-l-Leu-l-Trp-OBn；L-leucyl-L-tryptophan benzyl ester；benzyl (2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate
• CAS: 152290-27-2
• 化学式: C₂₄H₂₉N₃O₃
• 分子量: 407.513
• InChiKey: QXLRICDXUQQAMR-UNMCSNQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  97.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  L-leucine-L-tryptophan benzyl ester 在 5%-palladium/activated carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成
  参考文献：
  名称：

  Synthesis and enzymatic evaluation of phosphoramidon and its β anomer: Anomerization of α-l-rhamnose triacetate upon phosphitylation

  摘要：

  A novel and efficient strategy for the synthesis of phosphoramidon and its beta anomer has been developed by manipulating the anomerization of alpha-L-rhamnose triacetate upon phosphitylation. The experimental results suggest that proton transfer, bond rotation, and N atom are the key factors for the anomerization. The determined K-i and K-d values establish that phosphoramidon prepared by this method possesses excellent biological activity, and indicate that the contacts of rhamnose moiety with the enzyme have limited contribution to the binding. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.052
• 作为产物：
  描述：

  Boc-Leu-HONB 在 三氟乙酸 作用下， 以 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 13.0h， 生成 L-leucine-L-tryptophan benzyl ester
  参考文献：
  名称：

  Application of a Unique Automated Synthesis System for Solution-phase Peptide Synthesis.

  摘要：

  使用了一种适合于采用相似反应程序进行重复合成的自动化合成系统，系统性地合成了由5种保护氨基酸组成的所有可能的二肽（25种）和三肽（125种）库。该装置还被应用于10种激素PACAP-27成分片段三肽衍生物的自动化合成。实验测得125种三肽库的分光旋转值与通过各成分氨基酸的分光旋转值总和计算得到的值相关性良好。

  DOI：

  10.1248/cpb.43.1272

文献信息

• Aminophosphonic acid derivative
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP0623625A1

  公开（公告）日：1994-11-09

  There are provided novel aminophosphonic acid derivatives of the general formula [I]: wherein n is an integer of 2 or 3; R¹ is a phenyl, naphthyl, indolyl, benzothienyl, benzofuryl or benzoxazolyl group which may have 1 to 3 substituents selected from the group consisting of hydroxyl and lower alkyloxy groups, or a hydrogen atom; R² is a lower alkyl group, a benzyl group, a 4-hydroxybenzyl group, a 3-indolylmethyl group or a β-phenethyl group; and A is an optional residue of an amino acid selected from the group consisting of tryptophane, tyrosine, phenylalanine, homophenylalanine, naphthylalanine or Nω-nitroarginine, and their pharmaceutically acceptable salts. The compounds according to the present invention and their pharmaceutically acceptable salts exhibit an inhibitory activity against endothelin-converting enzyme, and are expected to be useful as a drug treating various diseases with which endothelin is concerned.

  提供了一种新型的氨基膦酸衍生物，其一般式如下[I]：其中n是2或3的整数；R¹是苯基，萘基，吲哚基，苯并噻吩基，苯并呋喃基或苯并噁唑基，其可具有1至3个取自氢氧基和低烷氧基的取代基，或是氢原子；R²是低烷基，苄基，4-羟基苄基，3-吲哚甲基基或β-苯乙基；A是选自色氨酸，酪氨酸，苯丙氨酸，同型苯丙氨酸，萘氨酸或Nω-硝基精氨酸的氨基酸残基，以及它们的药学上可接受的盐。根据本发明的化合物及其药学上可接受的盐表现出对内皮素转化酶的抑制活性，预计可用于治疗与内皮素相关的各种疾病的药物。
• Aminophosponic acid derivative
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US05380921A1

  公开（公告）日：1995-01-10

  There are provided novel aminophosphonic acid derivatives of the general formula [I]: ##STR1## wherein n is an integer of 2 or 3; R.sup.1 is a phenyl, naphthyl, indolyl, benzothienyl, benzofuryl or benzoxazolyl group which may have 1 to 3 substituents selected from the group consisting of hydroxyl and lower alkyloxy groups, or a hydrogen atom; R.sup.2 is a lower alkyl group, a benzyl group, a 4-hydroxybenzyl group, a 3-indolylmethyl group or a .beta.-phenethyl group; and A is an optional residue of an amino acid selected from the group consisting of tryptophane, tyrosine, phenylalanine, homophenylalanine, naphthylalanine or N.sup..omega. -nitroarginine, and their pharmaceutically acceptable salts. The compounds according to the present invention and their pharmaceutically acceptable salts exhibit an inhibitory activity against endothelin-converting enzyme, and are expected to be useful as a drug treating various diseases with which endothelin is concerned.

  提供了一种一般式[I]的新型氨基膦酸衍生物：其中n是2或3的整数；R.sup.1是苯基、萘基、吲哚基、苯并噻吩基、苯并呋喃基或苯并噁唑基，可能具有1至3个亚羟基和较低的烷氧基从羟基和较低的烷氧基中选择的取代基，或氢原子；R.sup.2是较低的烷基、苄基、4-羟基苄基、3-吲哚甲基基团或β-苯乙基基团；A是从色氨酸、酪氨酸、苯丙氨酸、同苯丙氨酸、萘丙氨酸或N.ω.-硝基精氨酸中选择的氨基酸的可选残基和它们的药用盐。根据本发明的化合物及其药用盐对内皮素转化酶表现出抑制活性，并有望作为治疗涉及内皮素的各种疾病的药物。
• An Improved<i>H</i>-Phosphonate Approach for Practical Synthesis of Phosphoramidon
  作者：Qi Sun、Qingkun Yang、Shanshan Gong、Jian Sun、Xingjian Li、Guodong Liu

  DOI：10.1080/10426507.2014.902829

  日期：2014.12.2

  An improved synthetic method based on glycosyl-1-H-phosphonate monoester intermediate has been developed for the multigram-scale preparation of phosphoramidon, a naturally occurring phosphorus-linked glycodipeptide. The inhibitor constant of the synthetic sample against thermolysin established that a high level of biological activity can be obtained following this synthetic method.
• Effects of metalloprotease inhibitors on smooth muscle endothelindashconverting enzyme activity
  作者：Joseph L. Balwierczak、Paivi J. Kukkola、Paula Savage、Arco Y. Jeng

  DOI：10.1016/0006-2952(94)00508-j

  日期：1995.1

  The enzyme responsible for the conversion of exogenous big endotheIin-1 to endothelin-1 by porcine coronary arterial smooth muscle has been shown to be a metalloprotease. The potencies of eight metalloprotease inhibitors for this endothelin-converting enzyme were determined. CGS 25015, CGS 26129, and thiorphan inhibited the enzyme activity monophasically with IC50 values of 2.6, 2.4, and 190 mu M, respectively. In contrast, the data obtained using phosphoramidon as an inhibitor were best fit by a two-site model. The biphasic concentration-response curve had IC50 values of 4.6 mu M and 2.2 mM. Three analogs of phosphoramidon were also tested for enzyme inhibition. Removal of the rhamnose moiety of phosphoramidon reduced the potency (IC50 = 15 mu M), whereas substitution of the rhamnose by N-[2-(2-naphthyl)ethyl] improved the potency (IC50 = 2.0 mu M). These results identify a thiol and a phosphonyl series of compounds as smooth muscle endothelin-converting enzyme inhibitors. The structure-activity relationships revealed that an aromatic or aliphatic group in the P-2' position or an aromatic group in the P-1 position of the inhibitor significantly increased the potency.
• US5380921A
  申请人：——

  公开号：US5380921A

  公开（公告）日：1995-01-10