3(S)-amino-2(R,S)-hydroxy-4-phenylbutyric acid methyl ester | 209174-37-8

• 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: 3(S)-amino-2(R,S)-hydroxy-4-phenylbutyric acid methyl ester
• 英文别名: methyl (3S)-3-amino-2-hydroxy-4-phenylbutanoate
• CAS: 209174-37-8
• 化学式: C₁₁H₁₅NO₃
• 分子量: 209.245
• InChiKey: LAHWVQFOBUUDBA-RGURZIINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3(S)-amino-2(R,S)-hydroxy-4-phenylbutyric acid methyl ester 在 N-甲基吗啉 、 盐酸 、 sodium hydroxide 、 TEA 、 sodium cyanoborohydride 、 1-羟基苯并三唑 、 一水合肼 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 53.0h， 生成 N'N'-(benzyl)(tert-butyloxycarbonylamino)-3(S)-(N-Cbz-leucylamino)-2(R,S)-hydroxy-4-phenylbutanoic acid hydrazide
  参考文献：
  名称：

  Design, Synthesis, Molecular Modeling Studies, and Calpain Inhibitory Activity of Novel α-Ketoamides Incorporating Polar Residues at the P₁‘-Position

  摘要：

  A series of novel alpha-ketoamides incorporating stereoisomeric residues with different electronic properties at the P-1'-position were synthesized to study the electronic requirements for inhibitor binding to the S-1'-subsite of calpain I. The results of the study suggested the presence of an acidic amino acid residue at the S-1'-subsite of calpain I. For example, ester la (CbZ-L-Leu-L-Phe-CO-D-Phe-OMe) was over 450-fold more potent than its carboxylic acid derivative 2a (Cbz-L-Leu-L-Phe-CO-D-Phe-OH). Additionally, amidino derivative 3a (CbZ-L-Leu-L-Phe-CONH-D-CH[C(NH)NH2]Bn) was about 6000-fold more potent than 2a. Furthermore, 4a (Cbz-L-Leu-L-Phe-CONHCH2Bn) was 12-fold less potent than its aza analogue 4b (CbZ-L-Leu-L-Phe-CONHNHBn). The results are consistent with the presence of an acidic amino acid residue at the S-1'-subsite of calpain I. The acidic amino acid residue was found to be Glu261 via molecular modeling studies.

  DOI：

  10.1021/jm0301336
• 作为产物：
  描述：

  N-Boc-L-苯丙氨醛 在 氯化亚砜 、 benzylcinchoninium chloride 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 3(S)-amino-2(R,S)-hydroxy-4-phenylbutyric acid methyl ester
  参考文献：
  名称：

  A concise synthesis of aza-dipeptide isosteres

  摘要：

  Aza-dipeptide isosteres as potent HIV-protease inhibitors containing a (hydroxyethyl)-hydrazine moiety are synthesised in >98% diastereomeric and enantiomeric purity starting from (L)-phenylalanine aldehyde. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)00897-1

文献信息

• DIPEPTIDYL KETOAMIDE META-METHOXYPHENYL DERIVATIVES AND USES THEREOF
  申请人：LANDSTEINER GENMED, S.L.

  公开号：EP3564211A1

  公开（公告）日：2019-11-06

  The present invention relates to dipeptidyl ketoamide m-methoxyphenyl derivatives and their use in the treatment of diseases and conditions associated with elevated calpain activity, such as heart injury caused by infarction, ischemia with or without reperfusion, neurodegenerative disorders, malaria, diabetic nephropathy, neurotoxicity induced by HIV virus, and cancer.

  本发明涉及二肽基酮甲氧基苯衍生物及其在治疗与卡尔帕因活性升高相关的疾病和病况中的应用，如因梗死引起的心脏损伤、缺血伴或不伴再灌注、神经退行性疾病、疟疾、糖尿病肾病、HIV病毒诱导的神经毒性和癌症。
• Dipeptidyl ketoamide meta-methoxyphenyl derivatives and uses thereof
  申请人：LANDSTEINER GENMED, S.L.

  公开号：US11242312B2

  公开（公告）日：2022-02-08

  The present invention relates to dipeptidyl ketoamide m-methoxyphenyl derivatives and their use in the treatment of diseases and conditions associated with elevated calpain activity, such as heart injury caused by infarction, ischemia with or without reperfusion, neurodegenerative disorders, malaria, diabetic nephropathy, neurotoxicity induced by HIV virus, cancer, and fibrotic diseases.

  本发明涉及二肽基酮酰胺间甲氧基苯基衍生物及其在治疗与钙蛋白酶活性升高有关的疾病和病症中的用途，例如梗塞、有或无再灌注的缺血引起的心脏损伤、神经退行性疾病、疟疾、糖尿病肾病、HIV 病毒诱导的神经毒性、癌症和纤维化疾病。
• WO2008/97676
  申请人：——

  公开号：——

  公开（公告）日：——
• Papain-catalyzed synthesis of peptide isosteres
  作者：M. Schuster、B. Munoz、W. Yuan、C.-H. Wong

  DOI：10.1016/s0040-4039(00)91765-9

  日期：1993.2

  The thiol protease papain catalyses the transfer of the Cbz-Gly moiety from the donor substrate Cbz-Gly-OMe to the amino group of various alpha-hydroxy- and alpha-keto-amines, providing a new route to peptide isosteres.
• PYRROLOPYRIDINE-2-CARBOXYLIC ACID AMIDE INHIBITORS OF GLYCOGEN PHOSHORYLASE
  申请人：Prosidion Limited

  公开号：EP1636224B1

  公开（公告）日：2010-07-14