2-(R,S)-benzyl-3-benzyloxyamino-propionic acid | 96866-14-7

• 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: 2-(R,S)-benzyl-3-benzyloxyamino-propionic acid
• 英文别名: 3(RS)-<(benzyloxy)amino>-2-benzylpropanoic acid；3-benzyloxyamino 2-benzyl propanoic acid；3(RS)-[(benzyloxy)amino]-2-benzylpropanoic acid；2-benzyl-3-(phenylmethoxyamino)propanoic acid
• CAS: 96866-14-7
• 化学式: C₁₇H₁₉NO₃
• 分子量: 285.343
• InChiKey: LMWFAGWEXPVAJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(R,S)-benzyl-3-benzyloxyamino-propionic acid 在 麻黄碱 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 ethyl 2-[(6S)-6-[[(2R)-2-benzyl-3-(phenylmethoxyamino)propanoyl]amino]-2,2-dimethyl-7-oxoazepan-1-yl]acetate
  参考文献：
  名称：

  N -Formyl hydroxylamine containing dipeptides: generation of a new class of vasopeptidase inhibitors

  摘要：

  Four primary zinc-binding pharmacophores (thiols, carboxylates, phosphorus acids, and hydroxamates) have been utilized in generating inhibitors of zinc metalloproteases such as ACE, NEP, the MMPs, and ECE. Although compounds which inhibit the activity of both ACE and NEP (vasopeptidase inhibitors, VPIs) have been reported which incorporate a thiol, carboxylate, or phosphorus acid pharmacophore, the generation of hydroxamate based vasopeptidase inhibitors has remained elusive. Herein we report the first potent vasopeptidase inhibitors which were generated from the incorporation of conformationally restricted dipeptide mimetics to an N-formyl hydroxylamine zinc-binding group. Compounds such as 13c and 13d are among the most potent in this series, exhibiting in vitro activity comparable to other classes of inhibitors. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00671-x
• 作为产物：
  描述：

  N-benzyloxy-3-benzyl-2-azetidinone 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以99%的产率得到2-(R,S)-benzyl-3-benzyloxyamino-propionic acid
  参考文献：
  名称：

  First hydroxamate inhibitors for carboxypeptidase A. N-Acyl-N-hydroxy-β-phenylalanines

  摘要：

  A series of N-acyl-N-hydroxy-beta-Phe were designed, synthesized, and shown to have potent inhibitory activity for carboxypeptidase A (CPA). They are the first examples of CPA inhibitors having a hydroxamate functionality. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00055-4

文献信息

• N-formyl hydroxylamine containing compounds useful as ACE inhibitors and/or NEP inhibitors
  申请人：Bristol-Myers Squibb Company

  公开号：US06777550B1

  公开（公告）日：2004-08-17

  N-formyl hydroxylamines are provided which have the structure wherein R is H, alkyl, alkenyl, aryl-(CH2)p—, heteroaryl-(CH2)p— or cycloheteroalkyl-(CH2)p— R1 is H or COR2 where R2 is alkyl, aryl-(CH2)p—, cycloheteroalkyl-(CH2)p—, heteroaryl-(CH2)p—, alkoxy or cycloalkyl-(CH2)p—, p is 0 to 8, and A is a dipeptide derived from an amino acid or is a conformationally restricted dipeptide mimic. The above compounds are useful in treating hypertension congestive heart failure, renal failure, and hepatic cirrhosis.

  提供了具有以下结构的N-甲酰羟胺，其中R为H，烷基，烯基，芳基-(CH2)p—，杂芳基-(CH2)p—或环杂芳基-(CH2)p—；R1为H或COR2，其中R2为烷基，芳基-(CH2)p—，环杂芳基-(CH2)p—，杂芳基-(CH2)p—，烷氧基或环烷基-(CH2)p—；p为0至8，A为来源于氨基酸的二肽或是具有构象限制的二肽模拟物。上述化合物在治疗高血压、充血性心力衰竭、肾功能衰竭和肝硬化方面具有用途。
• N-formyl hydroxylamine derivatives as antibacterial agents
  申请人：British Biotech

  公开号：US06476067B1

  公开（公告）日：2002-11-05

  Compounds of formula (I) are in the preparation of antibacterial agents, wherein: R1 represents hydrogen, C1-C6 alkyl or C1-C6 alkyl substituted by one or more halogen atoms; R2 represents a group R10(X)n—(ALK)— wherein R10 represents hydrogen, a C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkynyl, cycloalkyl, aryl, or heterocyclyl group, any of which may be unsubstituted or substituted by (C1-C6)alkyl, (C1-C6)alkoyy, hydroxy, mercapto, (C1-C6)alkylthio, amino, halo, trifluoromethyl, cyano, nitro, —COOH, —CONH2, —COORA, —NHCORA, —CONHRA, —NHRA, —NRARB, or —CONRARB wherein RA and RB are independently a (C1-C6)alkyl group, and ALK represents a straight or branched divalent C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene radical, which may be interrupted by one or more non-adjacent —NH—, —O— or —S— linkages, X represents —NH—, —O— or —S—, and n is 0 or 1, R represents hydrogen or C1-C6 alkyl, R3 represents the characterising group or a natural or non-natural &agr; amino acid in which any functional groups may be protected; and R4 represents an ester or thioester group.

  式(I)的化合物用于制备抗菌剂，其中：R1代表氢，C1-C6烷基或C1-C6烷基上取代一个或多个卤素原子；R2代表一个基团R10（X）n—（ALK）—，其中R10代表氢，C1-C6烷基，C2-C6烯基，C1-C6炔基，环烷基，芳基或杂环基，任何一个可以未取代或取代为（C1-C6）烷基，（C1-C6）烷氧基，羟基，巯基，（C1-C6）烷基硫基，氨基，卤素，三氟甲基，氰基，硝基，—COOH，—CONH2，—COORA，—NHCORA，—CONHRA，—NHRA，—NRARB或—CONRARB，其中RA和RB分别为（C1-C6）烷基基团，ALK代表直链或支链二价的C1-C6烷基，C2-C6烯基或C2-C6炔基基团，可以由一个或多个非相邻的—NH—，—O—或—S—连接中断，X代表—NH—，—O—或—S—，n为0或1，R代表氢或C1-C6烷基，R3代表表征基团或一种天然或非天然的α-氨基酸，其中任何功能基团均可保护；R4代表酯或硫酯基团。
• Cytostatic agents
  申请人：British Biotech Pharmaceuticals Ltd.

  公开号：US06495597B1

  公开（公告）日：2002-12-17

  Compounds of formula (I) wherein R4 is an ester or thioester group and R, R1, R2 and R3 are as defined in the specification, inhibit proliferation of tumor cells.

  式(I)中的化合物，其中R4是酯或硫酯基团，R、R1、R2和R3如规范中所定义，能够抑制肿瘤细胞的增殖。
• New bidentates as full inhibitors of enkephalin-degrading enzymes: synthesis and analgesic properties
  作者：Marie Claude Fournie-Zaluski、Annie Coulaud、Romaine Bouboutou、Pierre Chaillet、Jocelyne Devin、Gilles Waksman、Jean Costentin、Bernard P. Roques

  DOI：10.1021/jm00147a007

  日期：1985.9

  New compounds were designed to fully inhibit the in vitro metabolism of enkephalins, ensured by three different metallopeptidases. For this purpose, bidentate ligands as hydroxamate and N-hydroxy-N-formylamino groups were selected as highly potent metal coordinating agents and introduced on Phe-Gly and Phe-Ala related structures. Compounds corresponding to the general formula HC(O)N(OH)CH2CH(CH2Ph)CONHCH2COOH (compound 7) and HN(OH)C(O)CH2CH(CH2Ph)CONHCH(R)COOH (compound 11, R = H; compound 13, R = CH3) behave as full inhibitors of the three enzymes, with IC50's in the nanomolar range for enkephalinase, from 0.3 microM to 1 nM for dipeptidylaminopeptidase, and in the micromolar range for a biologically relevant aminopeptidase. Two diastereoisomers of the most active inhibitor 13 were separated by HPLC and their stereochemistry was assigned by 1H NMR spectroscopy. Both isomers were efficient as enkephalinase blockers, but only the RS isomer, designated kelatorphan, was able to strongly inhibit aminopeptidase and dipeptidylaminopeptidase. Intracerebroventricular injection in mice of these mixed inhibitors, especially kelatorphan, led to naloxone reversible analgesic responses (hot-plate test) that were slightly better than those produced by a mixture of thiorphan and bestatin, two potent inhibitors of enkephalinase and aminopeptidase, respectively. Kelatorphan was also more efficient in potentiating the analgesia induced by a subanalgesic dose of Met-enkephalin. All these results support a physiological role in pain transmission for enkephalinase and a probably synaptic aminopeptidase M.
• CYTOSTATIC AGENTS
  申请人：BRITISH BIOTECH PHARMACEUTICALS LIMITED

  公开号：EP1054861A1

  公开（公告）日：2000-11-29