(O-Me)Hser-OMe*HCl | 85918-14-5

• 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: (O-Me)Hser-OMe*HCl
• 英文别名: O-methyl homoserine methyl ester hydrochloride；methyl (2S)-2-amino-4-methoxybutanoate;hydrochloride
• CAS: 85918-14-5
• 化学式: C₆H₁₃NO₃*ClH
• 分子量: 183.635
• InChiKey: JMSUJLCRZXUOGD-JEDNCBNOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.05
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  61.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (O-Me)Hser-OMe*HCl 、 Boc-Leu-O-COO-isoBu 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 Boc-Leu-Hse(CH3)-OCH3
  参考文献：
  名称：

  Synthesis of an analogue of the substance P C-terminal hexapeptide with modification at the glutaminyl and methioninyl residues and increased activity in NK-2 receptor type: Structure-activity relationships

  摘要：

  Analogues of [Orn6]-Sp6-11 have been synthesized in which the Met11 residue is replaced by Hse(CH3), Hse(Bzl), Nva(5-OCH3), Nva(5-OBzl) and Abu. These analogues were tested in 3 in vitro preparations representative of NK-1, NK-2 and NK-3 receptor types. The Hse(Bzl) analogue is 16.6-fold more potent than the parent hexapeptide at the NK-2 receptor and 2.4-fold more potent at the NK-3 receptor. The Nva(5-OCH3) analogues howed weak antagonist activity in NK-2 and NK-3 receptor types, being a full agonist at NK-1. It is concluded from structure-activity correlations that the role of Met11 side chain in substance P is associated with activity and/or efficacy, as appropriate modifications in the side chain may result either in agonists with increased activity compared to the parent hexapeptide or selective agonists or may induce antagonism.

  DOI：

  10.1016/0223-5234(92)90027-x
• 作为产物：
  描述：

  甲醇 、 N-Trt-Hser 在 盐酸 作用下， 反应 6.0h， 以92%的产率得到(O-Me)Hser-OMe*HCl
  参考文献：
  名称：

  n-三苯甲基-o-烷基-1-羟基氨基酸及其衍生物的便捷合成：在相关肽的合成中的应用

  摘要：

  在咪唑存在下用NaH原位制备的N-三苯甲基-羟基氨基酸2的二钠盐用烷基碘选择性地烷基化，得到N-三苯甲基-O-烷基-羟基氨基酸3。化合物3易于转化为O-烷基-羟基氨基酸5或用于掺入肽链的其他中间体。这些衍生物在相关肽的制备中的适用性通过脑啡肽N-碳苯甲氧基-酪氨酰-甘氨酰-甘氨酰-苯丙氨酰基-（O-乙基）丝氨酸苄基酯和N-碳苯甲氧基-酪氨酰-甘氨酰的保护类似物的合成来说明。 -甘氨酰基-苯丙氨酰基-（O-甲基）高丝氨酸苄基酯。

  DOI：

  10.1016/s0040-4020(01)88549-5

文献信息

• N-Adamantane-substituted tetrapeptide amides
  申请人：G. D. Searle & Co.

  公开号：US04273704A1

  公开（公告）日：1981-06-16

  N-Adamantane-substituted tetrapeptide amides and the pharmacologically acceptable salts thereof are disclosed herein. These compounds are analogs of enkephalin wherein the methionine or leucine of position 5 has been substituted by an adamantyl amide and the glycine of position 2 has been substituted by various amino acid residues. Optionally the tyrosine of position 1 and the phenylalanine of position 4 may be substituted by various amino acid residues. These compounds exhibit agonist activity at opiate receptor sites and are useful as analgesics.

  本文披露了N-金刚烷取代的四肽酰胺及其药理学上可接受的盐。这些化合物是脑啡肽的类似物，其中第5位的蛋氨酸或亮氨酸被金刚烷酰胺替代，第2位的甘氨酸被各种氨基酸残基替代。选项地，第1位的酪氨酸和第4位的苯丙氨酸可以被各种氨基酸残基替代。这些化合物在鸦片受体位点表现出激动剂活性，并可用作镇痛剂。
• 一种制备O-甲基-N-苄氧羰基-L-高丝氨酸的方法
  申请人：爱斯特（成都）生物制药股份有限公司

  公开号：CN116813505A

  公开（公告）日：2023-09-29

  本发明提供了一种制备O‑甲基‑N‑苄氧羰基‑L‑高丝氨酸的方法，涉及有机合成领域。本发明制备方法包括如下步骤：(1)溶剂中，化合物1、碱和二碳酸二叔丁酯反应，得到化合物2；(2)溶剂中，化合物2、碱和硫酸二甲酯反应，得到化合物3；(3)溶剂中，化合物3和氯化亚砜反应，得到化合物4；(4)溶剂中，化合物4和氯甲酸苄酯在碱性环境下反应，得化合物5；(5)溶剂中，化合物5和碱反应，即得。本发明使用的原料易得且价格低，反应条件温和，中间反应步骤无需纯化，且无需柱层析分离，步骤简单；并且本发明涉及的反应步骤安全无毒，绿色环保。本发明制备方法得到的产物纯度高，收率高，成本低，适合放大生产，应用前景广阔。#imgabs0#
• Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3 SAR
  作者：Jason Lamar、Jingdan Hu、Ana Belen Bueno、Hsiu-Chiung Yang、Deqi Guo、James D. Copp、James McGee、Bruce Gitter、David Timm、Patrick May、James McCarthy、Shu-Hui Chen

  DOI：10.1016/j.bmcl.2003.09.084

  日期：2004.1

  We describe herein the syntheses and evaluation of a series of C-termini pyridyl containing Phe*-Ala-based BACE inhibitors (5-19). In conjunction with four fixed residues at the P1 (Phe), P1' (Ala), P2' (Val), and P2' cap (Pyr.), rather detailed SAR modifications at P2 and P3 positions were pursued. The promising inhibitors emerging from this SAR investigation, 12 and 17 demonstrated very good enzyme potency (IC50 = 45 nM) and cellular activity (IC50 = 0.4 muM). (C) 2003 Elsevier Ltd. All rights reserved.
• Potent and Selective Non-Cysteine-Containing Inhibitors of Protein Farnesyltransferase
  作者：David J. Augeri、Stephen J. O'Connor、Dave Janowick、Bruce Szczepankiewicz、Gerry Sullivan、John Larsen、Douglas Kalvin、Jerry Cohen、Edward Devine、Haichao Zhang、Sajeev Cherian、Badr Saeed、Shi-Chung Ng、Saul Rosenberg

  DOI：10.1021/jm980298s

  日期：1998.10.1

  Potent and selective non-thiol-containing inhibitors of protein farnesyltransferase are described. FTI-276 (1) was transformed into pyridyl ether analogue 19. The potency of pyridyl ether 19 was improved by modification of the biphenyl core to that of an o-tolyl substituted biphenyl core to give 29. In addition to 0.4 nM in vitro potency, 29 displayed 350 nM potency in whole cells as the parent carboxylic acid. The o-tolyl biphenyl core dramatically and unexpectedly enhanced the potency of other compounds as exemplified by 46, 47, 48, and 49.
• Synthesis of an analogue of the substance P C-terminal hexapeptide with modification at the glutaminyl and methioninyl residues and increased activity in NK-2 receptor type: Structure-activity relationships
  作者：A Manolopoulou、C Poulos、T Tsegenidis

  DOI：10.1016/0223-5234(92)90027-x

  日期：1992.12

  Analogues of [Orn6]-Sp6-11 have been synthesized in which the Met11 residue is replaced by Hse(CH3), Hse(Bzl), Nva(5-OCH3), Nva(5-OBzl) and Abu. These analogues were tested in 3 in vitro preparations representative of NK-1, NK-2 and NK-3 receptor types. The Hse(Bzl) analogue is 16.6-fold more potent than the parent hexapeptide at the NK-2 receptor and 2.4-fold more potent at the NK-3 receptor. The Nva(5-OCH3) analogues howed weak antagonist activity in NK-2 and NK-3 receptor types, being a full agonist at NK-1. It is concluded from structure-activity correlations that the role of Met11 side chain in substance P is associated with activity and/or efficacy, as appropriate modifications in the side chain may result either in agonists with increased activity compared to the parent hexapeptide or selective agonists or may induce antagonism.