N-benzyloxy-L-phenylalanine | 96866-10-3

• 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: N-benzyloxy-L-phenylalanine
• 英文别名: N-benzyloxy phenylalanine；N-(Benzyloxy)-L-phenylalanine；(2S)-3-phenyl-2-(phenylmethoxyamino)propanoic acid
• CAS: 96866-10-3
• 化学式: C₁₆H₁₇NO₃
• 分子量: 271.316
• InChiKey: ISEBNIQQPMISGA-HNNXBMFYSA-N

物化性质

• 沸点：
  441.0±55.0 °C(Predicted)
• 密度：
  1.199±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 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：

  N-benzyloxy-L-phenylalanine 在 乙酸酐 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 3.0h， 生成 N-(benzyloxy)-N-formyl-L-phenylalanylglycine benzyl ester
  参考文献：
  名称：

  New bidentates as full inhibitors of enkephalin-degrading enzymes: synthesis and analgesic properties

  摘要：

  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.

  DOI：

  10.1021/jm00147a007
• 作为产物：
  描述：

  D-苯丙氨酸 在 sodium hydroxide 、 PTS*H₂O 、 硫酸 、 碳酸氢钠 、 potassium bromide 、 sodium nitrite 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 N-benzyloxy-L-phenylalanine
  参考文献：
  名称：

  Synthesis and activity of HIV protease inhibitors

  摘要：

  We report here the synthesis and activity of HIV protease inhibitors. Ln the first stage hydrophobic compounds incorporating a 'carba' bond surrogate or a beta-homologated residue were synthesized. Secondly, we synthesized cyclic compounds in which we incorporated 2-quinoline carboxylic acid in the P3 position and the amino-hydroxyindane moiety in the P'3. The last part of this work was dedicated to a structure/activity study of a peptide substrate. These modifications allowed us to work up the synthesis of new pseudopeptide bonds: amino-amide and hydroxy-amide, Compounds with activity in the micromolar range were actually a starting point for the synthesis of new protease inhibitors. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80043-3

文献信息

• [EN] COMT INHIBITING METHODS AND COMPOSITIONS<br/>[FR] MÉTHODES ET COMPOSITIONS D'INHIBITION DE COMT
  申请人：LIEBER INST FOR BRAIN DEV

  公开号：WO2017091818A1

  公开（公告）日：2017-06-01

  Compounds that inhibit COMT enzyme and pharmaceutical compositions comprising the same are provided herein. Methods of treating various psychiatric and neurological disorders with the compounds and pharmaceutical compositions described herein are also provided.

  本文提供了抑制COMT酶的化合物以及包含这些化合物的药物组合物。还提供了使用这些化合物和药物组合物治疗各种精神疾病和神经疾病的方法。
• HIV-1 protease inhibitors containing an N-Hydroxyamino acid core structure
  作者：Mauro Marastoni、Martina Bazzaro、Severo Salvadori、Fabrizio Bortolotti、Roberto Tomatis

  DOI：10.1016/s0968-0896(00)00308-4

  日期：2001.4

  Two series of peptidomimetics containing an N-hydroxyamino acid core structure were prepared by mixed solution solid-phase synthesis and tested for inhibitory activity against the human immunodeficiency virus (HIV-1) protease (Pr) and the virus in cell culture. In general, N-hydroxy Gly containing pseudopeptides displayed modest HIV Pr inhibition (IC50 > or = 930 nM). In the N-hydroxy Phe derivatives

  通过混合溶液固相合成制备了两个系列的包含N-羟基氨基酸核心结构的拟肽，并在细胞培养中测试了对人免疫缺陷病毒（HIV-1）蛋白酶（Pr）和该病毒的抑制活性。通常，含有N-羟基甘氨酸的假肽显示出适度的HIV Pr抑制（IC50>或= 930 nM）。在N-羟基Phe衍生物中，Fmoc-Phe-psi [CO-N（OH）]-Phe-Pro-NHtBu是该系列的最佳抑制剂（IC50 = 144nM），对细胞培养中的HIV复制具有抑制作用（ED50） = 98 nM），并且对细胞培养和血浆酶具有显着的稳定性。
• Phenylalanine derivative and proteinase inhibitor
  申请人：Okamoto, Shosuke

  公开号：EP0217286A1

  公开（公告）日：1987-04-08

  A phenylalanine derivative having the formula (I): where R' and R2 are independently hydrogen provided that both R' and R2 are nof hydrogen at the same time; C1-C5 alkyl which may be substituted with hydroxy, hydroxycarbonyl, C1-C4 alkoxycarbonyl, C1-C4 alkyl- mercapto, C,-C4 alkoxy, carbamoyl, sulfamoyl, pyridyl, or phenyl which may further be substituted with nitro, C1-C4 alkoxy, or halogen; C6-C3 cycloalkyl which may be substituted with hydroxy, C1-C4 alkoxy, hydroxylcarbonyl, C1-C4 alkoxycarbonyl, or C1-C4 alkyl; phenyl which may be substituted with halogen, nitro, trifluoromethyl, C,-C4 alkoxy, C1-C4 alkylmer- capto, C1-C4 alkylcarbonyl, phenylcarbonyl, hydroxycarbonyl, C1-C4 alkoxycarbonyl, carbamoyl, sulfamoyl, amidino, pyridylcarbonyl, or C1-C6 alkyl which may further be substituted with C1-C4 alkylcarbonyl, hydroxycarbonyl, or C1-C4 alkoxycarbonyl; pyridyl which may be substituted with halogen or C1-C4 alkoxy; pyrimidyl; N-benzylazacyclohexyl; and R' and R2 may form with the nitrogen atom attached thereto a ring structure as morpholino; thiomorpholino; or piperidyl which may be substituted with phenylcarbonyl, benzyl, or C1-C4 alkyl; pyrrolidyl which may be substituted with hydroxycarbonyl or C1-C4 alkoxycarbonyl; and piperidine substituted with C1-C4 alkyl, phenyl C1-C4 alkyl, phenylcarbonyl, or C,-C4 alkoxycarbonyl; X is hydrogen; nitro; amino; or -OZ wherein Z is hydrogen: C1-C4 alkyl; C2-C4 alkenyl; benzyl which may be substituted with halogen, C1-C4 alkyl, nitro, trifluoromethyl, hydroxycarbonyl, C1-C4 alkoxycarbonyl, or cyano; phenylcarbonylmethyl, pyridylmethyl; phenyl which may be substituted with nitro or halogen; pyridyl or pyrimidyl which may be substituted with nitro; phenylsulfonyl which may be substituted with C1-C4 alkyl; or benzyloxycarbonyl which may be substituted with halogen; n is 4 to 10; and the mark indicates that the configuration of the carbon may be either one of D-configuration, L-configuration and DL-configuration or a pharmaceutical acceptable salt thereof. This phenylalanine derivative is effective as a proteinase inhibitor.

  具有式（I）的苯丙氨酸衍生物： 其中 R' 和 R2 独立地为氢，但 R' 和 R2 不能同时为氢； 可被羟基、羟羰基、C1-C4 烷氧羰基、C1-C4 烷基-巯基、C,-C4 烷氧基、氨基甲酰基、氨基磺酰基、吡啶基或苯基取代的 C1-C5 烷基，可进一步被硝基、C1-C4 烷氧基或卤素取代； 可被羟基、C1-C4 烷氧基、羟基羰基、C1-C4 烷氧基羰基或 C1-C4 烷基取代的 C6-C3 环烷基； 可被卤素、硝基、三氟甲基、C,-C4 烷氧基、C1-C4 烷巯基、C1-C4 烷羰基、苯羰基、羟羰基、C1-C4 烷氧羰基、氨基甲酰基、氨基磺酰基、脒基、吡啶羰基取代的苯基，或可进一步被 C1-C4 烷羰基、羟羰基或 C1-C4 烷氧羰基取代的 C1-C6 烷基； 可被卤素或 C1-C4 烷氧基取代的吡啶基 嘧啶基； N-苄基氮杂环己基；以及 R'和R2可与相连的氮原子形成环状结构，如吗啉基；硫代吗啉基；或可被苯甲酰、苄基或C1-C4烷基取代的哌啶基； 可被羟羰基或 C1-C4 烷氧基羰基取代的吡咯烷基；以及 被 C1-C4 烷基、苯基 C1-C4 烷基、苯基羰基或 C,-C4烷氧基羰基取代的哌啶； X 是氢；硝基；氨基；或-OZ，其中 Z 是氢：C1-C4烷基；C2-C4烯基；可被卤素、C1-C4烷基、硝基、三氟甲基、羟基羰基、C1-C4烷氧基羰基或氰基取代的苄基；苯基羰基甲基、吡啶基甲基；可被硝基或卤素取代的苯基；可被硝基取代的吡啶基或嘧啶基；可被C1-C4烷基取代的苯磺酰基；或可被卤素取代的苄氧羰基； n 为 4 至 10；以及 标记表示碳的构型可以是 D-构型、L-构型和 DL-构型之一或其药物可接受盐。 这种苯丙氨酸衍生物作为蛋白酶抑制剂是有效的。
• Nouveaux dérivés d'aminoacides, et leur application thérapeutique
  申请人：Roques, Bernard

  公开号：EP0082088B1

  公开（公告）日：1986-04-02
• LIBRARIES OF CONFORMATIONALLY CONSTRAINED PEPTIDES, CHIRAL AZACROWNS, AND PEPTIDOMIMETICS AND METHODS OF MAKING THE SAME
  申请人：Metaphore Pharmaceuticals Inc.

  公开号：EP1417219A2

  公开（公告）日：2004-05-12