N^α-benzyloxycarbonyl-N^α-methyl-O-benzyltyrosine | 95015-69-3

• 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^α-benzyloxycarbonyl-N^α-methyl-O-benzyltyrosine
• 英文别名: N-benzyloxycarbonyl-N-methyl-O-benzyl-L-tyrosine；Z-(Me)Tyr(Bzl)-OH；(S)-2-(((benzyloxy)carbonyl)(methyl)amino)-3-(4-(benzyloxy)phenyl)propanoic acid；(2S)-2-[methyl(phenylmethoxycarbonyl)amino]-3-(4-phenylmethoxyphenyl)propanoic acid
• CAS: 95015-69-3
• 化学式: C₂₅H₂₅NO₅
• 分子量: 419.477
• InChiKey: XQYZCRNBTXDHCJ-QHCPKHFHSA-N

物化性质

• 沸点：
  601.9±55.0 °C(Predicted)
• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N^α-benzyloxycarbonyl-N^α-methyl-O-benzyltyrosine 在 钯 盐酸 、 氢气 、 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 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.33h， 生成 N-(N^α-methyltyrosylleucyl-D-leucyl-D-leucyl)-1,8-octanediamine trifluoroacetate
  参考文献：
  名称：

  Design and Synthesis of Peptides Passing through the Blood-Brain Barrier

  摘要：

  血脑屏障（BBB）是一种高度选择性的膜屏障，调控血液中的物质向脑实质内的转运。目前，从脑部疾病化学治疗的角度出发，如何将生物活性肽或肽类药物递送入脑是一个相当重要的课题。首先合成了名为001-C8的H-MeTyr-Arg-MeArg-d-Leu-NH(CH2)8NH2，以阐明肽穿越BBB所需的结构特异性。在此肽中，Nα-甲基氨基酸和d-氨基酸残基适当地分布，以防止被肽酶降解。此外，还制备了一批001-C8类似物，即多种碱性肽，用于研究肽的结构与其BBB通透性之间的关系。

  DOI：

  10.1246/bcsj.71.699
• 作为产物：
  描述：

  O-苯基-N-叔丁基羰基-L-酪氨酸 在 三甲基氯硅烷 、 sodium cyanoborohydride 、 对甲苯磺酸 作用下， 以 乙腈 、 苯 为溶剂， 反应 0.08h， 生成 N^α-benzyloxycarbonyl-N^α-methyl-O-benzyltyrosine
  参考文献：
  名称：

  A Simple and Rapid Protocol forN-Methyl-α-Amino Acids

  摘要：

  描述了一种两步策略，从N-保护的α-氨基酸出发，通过使用NaCNBH3/TMSCl对恶唑烷酮进行还原性裂解，制备光学纯的N-保护-N-甲基-α-氨基酸。

  DOI：

  10.1246/cl.1999.299

文献信息

• Analgesic and/or opiate antagonist tripeptide amides and processes for
  申请人：Sterling Drug Inc.

  公开号：US04658013A1

  公开（公告）日：1987-04-14

  A genus of tripeptide amides and fifteen species thereof of Examples 4-18, which are useful as analgesics and/or opiate antagonists, three processes for preparation thereof, pharmaceutical compositions thereof, and the three tripeptide amide species of Examples 1-3, which are not within the genus and are useful as analgesics and/or opiate antagonists, are disclosed.

  一种三肽酰胺属及其15种物种，示例4-18，这些物种可用作止痛剂和/或阿片拮抗剂，其制备方法有三种，药物组合物，以及示例1-3的三种三肽酰胺物种，这些物种不属于该属，可用作止痛剂和/或阿片拮抗剂，均已披露。
• Amino acids and peptides. IV. Synthesis and analgesic effects of Tyr-containing dipeptide phenethylamides.
  作者：MITSUKO MAEDA、SATOSHI OKUSADA、KOICHI KAWASAKI

  DOI：10.1248/cpb.32.4157

  日期：——

  Several tyrosyl-5-aminovaleramide analogs were synthesized and their analgesic effects were examined. N-(Tyrosyl-5-aminovaleryl)-N-methylphenethylamine showed analgesic action in mice on peripheral administration.

  我们合成了几种酪氨酰-5-氨基戊酰胺类似物，并研究了它们的镇痛效果。N-（酪氨酰-5-氨基戊酰）-N-甲基苯乙胺在小鼠外周给药时显示出镇痛作用。
• Analgesic dipeptide amides and method of use and compositions thereof
  申请人：Sterling Drug Inc.

  公开号：US04533655A1

  公开（公告）日：1985-08-06

  A genus of dipeptide amides including as the preferred subgenus the dipeptide amides having the structural formula R.sub.1 TyrR.sub.2 D-AlaNHR.sub.4 wherein R.sub.1 and R.sub.2 are each hydrogen or alkyl provided that at least one of them is other than hydrogen and R.sub.4 is phenylalkyl or substituted-phenylalkyl are prepared by condensing the dipeptide with the amine or the amino acid with the amino acid amide and are useful as analgesics.

  这是一段化学术语的描述，翻译结果如下： 这是一类二肽酰胺的属，其中首选的亚属为具有结构式R.sub.1 TyrR.sub.2 D-AlaNHR.sub.4的二肽酰胺，其中R.sub.1和R.sub.2分别为氢或烷基，但至少有一个不是氢，而R.sub.4为苯基烷基或取代苯基烷基。这些二肽酰胺通过将二肽与胺或氨基酸酰胺缩合制备而成，并可用作镇痛剂。
• Intestinal absorption of fluorescence-derivatized cationic peptide 001-C8-NBD via adsorptive-mediated transcytosis
  作者：Yoshimichi Sai、Masahiro Kajita、Ikumi Tamai、Makoto Kamata、Jun Wakama、Tateaki Wakamiya、Akira Tsuji

  DOI：10.1016/s0968-0896(98)00031-5

  日期：1998.6

  The intestinal absorption of an intact oligopeptide was investigated in rats using a synthetic cationic peptide, 001-C8 (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)(8)NH2). The peptide was coupled with 4-nitrobenzo-2-oxa-1,3-diazole (NBD) to prepare a fluorescence-labeled derivative 001-C8-NBD (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)(8)NH-NBD) for the purpose of quantification, The degradation half-life of 001-C8-NBD in jejunal homogenate (1 mg/mL) was 99.5 min, which was significantly longer than that of natural leucine enkephalin (1.14 min). The absorption of 001-C8-NBD was evaluated by the vascular-perfusion method. Intact 001-C8-NBD appeared in the blood time-dependently and the absorption volume at 30 min (2.75 +/- 0.14 mu L/cm intestine) was significantly larger than that of [H-3]PEG 900 (0.88 +/- 0.13 mu L/cm intestine), of which membrane permeability is very low. The absorption of 001-C8-NBD was greatly reduced by an adsorptive-mediated endocytosis inhibitor, protamine (10 mM). No inhibition of the absorption of [H-3]PEG 900 by protamine was observed. The intestinal absorption was also measured by an in vivo loop method. The absorption clearance of 001-C8-NBD measured by this method (0.083 +/- 0.008 mu L/min/cm intestine) was comparable to that obtained by the vascular perfusion method (0.092 +/- 0.005 mu L/min/cm intestine). All of these data suggested that 001-C8-NBD was absorbed as the intact oligopeptide in the intestine in vivo. Adsorptive-mediated transcytosis is suggested to have enormous potential as an oral delivery system for peptide and/or protein drugs. (C) 1998 Elsevier Science Ltd. All rights reserved.
• US4533655A
  申请人：——

  公开号：US4533655A

  公开（公告）日：1985-08-06