L-3,5-dichloro-N-trifluoroacetyl tyrosine methyl ester | 105189-57-9

• 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: L-3,5-dichloro-N-trifluoroacetyl tyrosine methyl ester
• 英文别名: 3,5-dichloro-N-trifluoroacetyl-L-tyrosine methyl ester；methyl (2S)-3-(3,5-dichloro-4-hydroxyphenyl)-2-[(2,2,2-trifluoroacetyl)amino]propanoate
• CAS: 105189-57-9
• 化学式: C₁₂H₁₀Cl₂F₃NO₄
• 分子量: 360.117
• InChiKey: HWJQRVHVHWWAHD-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  L-3,5-dichloro-N-trifluoroacetyl tyrosine methyl ester 在 sodium acetate 作用下， 以 溶剂黄146 为溶剂， 生成 L-3,5-dichloro-O-methyl-3'-(6-oxo-3(1H)-pyridazinyl-methyl)-N-trifluoroacetyl-thyronine methyl ester
  参考文献：
  名称：

  Pyridyl and pyridazinyl substituted thyronine compounds having selective

  摘要：

  这项发明涉及具有选择性甲状腺激素活性的化合物。该发明的一种化合物是3,5-二溴-3'-[6-氧代-3(1H)-吡啶嗪基甲基]-甲状腺氨酸。

  公开号：

  US04766121A1

文献信息

• Selective thyromimetics. Cardiac-sparing thyroid hormone analogs containing 3'-arylmethyl substituents
  作者：Paul D. Leeson、John C. Emmett、Virendra P. Shah、Graham A. Showell、Ricardo Novelli、H. Douglas Prain、Martin G. Benson、David Ellis、Nigel J. Pearce、Anthony H. Underwood

  DOI：10.1021/jm00122a009

  日期：1989.2

  3'-arylmethyl T3 analogues show that electronegative groups at the para position increase both receptor binding and selectivity in vivo. However, increasing 3'-arylmethyl hydrophobicity increases receptor binding but reduces selectivity. Substitution at ortho and meta positions reduces both binding and selectivity. Replacement of the 3,5-iodo groups by halogen or methyl maintains selectivity, with 3

  在甲状腺激素3,3'，5-三碘-L-甲状腺素（T3）的3'位置引入特定的芳基甲基及其已知的激素活性衍生物，可提供对肝脏有选择性的，保心脏的甲状腺素用作血浆胆固醇降低剂。赋予选择性的3'-取代基包括取代的苄基，例如对羟基苄基，和杂环甲基，例如2-氧代-1,2-二氢吡啶-5-基甲基和6-氧代-1,6-二氢吡啶并-3-基甲基。体内和体外受体结合亲和力之间的相关性表明，肝脏/心脏的选择性不取决于受体的识别，而取决于体内受体的渗透或接近。QSAR研究一系列20 3'的结合数据 -芳基甲基T3类似物显示，对位的负电基团会增加体内的受体结合和选择性。但是，增加3'-芳基甲基疏水性会增加受体结合，但会降低选择性。在邻位和间位的取代减少了结合和选择性。3，5-碘基团被卤素或甲基取代可保持选择性，尤其是3，5-二溴类似物具有增强的效力和口服生物利用度。二苯基硫醚衍生物也具有改进的效力，但是口服活性较低。在1-
• Aromatic amino acid derivates and medicinal compositions
  申请人：Endo Hitoshi

  公开号：US20050119256A1

  公开（公告）日：2005-06-02

  1. An aromatic amino acid derivative represented by the formula (I) or its pharmacologically acceptable salt: wherein, R 1 is a hydrogen atom or an amino-protecting group, R 2 is a halogen atom or an alkyl, aralkyl or aryl group, R 3 is circle over (1)} a hydrogen atom, circle over (2)} an aroylamino group, circle over (3)} a phenyl group substituted with lower alkyl, phenyl, phenoxy, etc. circle over (4)} a naphthyl or tetrahydronaphthyl group optionally substituted with hydroxy, lower alkoxy or di(lower)alkylamino, circle over (5)} an unsaturated mono-cyclic heterocyclic group containing N, O and/or S substituted with lower alkyl, phenyl, naphthyl or tetrahydroquinolyl, circle over (6)} an unsaturated or partially saturated condensed heterocyclic group containing N, O and/or S, optionally substituted with oxo, carboxy, amino, lower alkyl, etc.; X is a halogen atom, an alkyl group or an alkoxy group; Y is oxygen atom or nitrogen atom; I is 0 or 1; m is 0, 1 or 2; n is an integer of 0-5. This compound can inhibit a transporter (LAT1) of essential amino acid which is one of main nutrition for cancer cells and accordingly cause drain of the essential amino acid on the cancer cells and finally can prohibit the multiplication of cancer cells.

  一种芳香族氨基酸衍生物，其化学式为（I）或其药理学上可接受的盐：其中，R1为氢原子或氨基保护基；R2为卤素原子或烷基、芳基烷基或芳基基团；R3为circle over (1)}氢原子，circle over (2)}芳基氨基基团，circle over (3)}苯基，其取代基为较低的烷基、苯基、苯氧基等，circle over (4)}萘基或四氢萘基，可选地取代羟基、较低的烷氧基或二（较低）烷基氨基，circle over (5)}含N、O和/或S的不饱和单环杂环基团，取代基为较低的烷基、苯基、萘基或四氢喹啉基团，circle over (6)}含N、O和/或S的不饱和或部分饱和的紧缩杂环基团，可选地取代为氧代、羧基、氨基、较低的烷基等；X为卤素原子、烷基或烷氧基；Y为氧原子或氮原子；I为0或1；m为0、1或2；n为0-5的整数。该化合物可以抑制癌细胞的主要营养物质之一的必需氨基酸转运体（LAT1），从而导致癌细胞必需氨基酸的流失，最终可以抑制癌细胞的增殖。
• Aromatic amino acid derivatives and medicinal compositions
  申请人：——

  公开号：US07345068B2

  公开（公告）日：2008-03-18

  1. An aromatic amino acid derivative represented by the formula (I) or its pharmacologically acceptable salt: wherein, R1 is a hydrogen atom or an amino-protecting group, R2 is a halogen atom or an alkyl, aralkyl or aryl group, R3 is circle around (1)} a hydrogen atom, circle around (2)} an aroylamino group, circle around (3)} a phenyl group substituted with lower alkyl, phenyl, phenoxy, etc. circle around (4)} a naphthyl or tetrahydronaphthyl group optionally substituted with hydroxy, lower alkoxy or di(lower)alkylamino, circle around (5)} an unsaturated mono-cyclic heterocyclic group containing N, O and/or S substituted with lower alkyl, phenyl, naphthyl or tetrahydroquinolyl, circle around (6)} an unsaturated or partially saturated condensed heterocyclic group containing N, O and/or S, optionally substituted with oxo, carboxy, amino, lower alkyl, etc.; X is a halogen atom, an alkyl group or an alkoxy group; Y is oxygen atom or nitrogen atom; l is 0 or 1; m is 0, 1 or 2; n is an integer of 0-5. This compound can inhibit a transporter (LAT1) of essential amino acid which is one of main nutrition for cancer cells and accordingly cause drain of the essential amino acid on the cancer cells and finally can prohibit the multiplication of cancer cells.

  一种芳香族氨基酸衍生物，其化学式为（I）或其药学上可接受的盐：其中，R1是氢原子或氨基保护基，R2是卤素原子或烷基、芳基烷基或芳基基团，R3是圆圈1}氢原子，圆圈2}芳酰氨基基团，圆圈3}苯基取代较低烷基、苯基、苯氧基等的基团，圆圈4}萘基或四氢萘基基团，可选地取代羟基、较低烷氧基或二（较低）烷基氨基，圆圈5}含有N、O和/或S的不饱和单环杂环基团，取代较低烷基、苯基、萘基或四氢喹啉基团，圆圈6}含有N、O和/或S的不饱和或部分饱和的紧缩杂环基团，可选地取代氧代、羧基、氨基、较低烷基等；X是卤素原子、烷基或烷氧基；Y是氧原子或氮原子；l为0或1；m为0、1或2；n为0-5的整数。该化合物可以抑制癌细胞的主要营养物质之一的必需氨基酸的转运体（LAT1），从而导致癌细胞中必需氨基酸的流失，最终可以抑制癌细胞的增殖。
• Chemical compounds
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：EP0188351B1

  公开（公告）日：1991-03-13
• AROMATIC AMINO ACID DERIVATIVES AND MEDICINAL COMPOSITIONS
  申请人：Endo, Hitoshi

  公开号：EP1481965B1

  公开（公告）日：2015-07-29