(S)-2-cyclohexyl-1-[(S)-2-(3,4-dihydroxyphenyl)-1-methoxycarbonylethyl-carbamoyl]-ethylammonium chloride

• 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: (S)-2-cyclohexyl-1-[(S)-2-(3,4-dihydroxyphenyl)-1-methoxycarbonylethyl-carbamoyl]-ethylammonium chloride
• 英文别名: H-Cha-Tyr(3-OH)-OMe.HCl；methyl (2S)-2-[[(2S)-2-amino-3-cyclohexylpropanoyl]amino]-3-(3,4-dihydroxyphenyl)propanoate;hydrochloride
• 化学式: C₁₉H₂₈N₂O₅*ClH
• 分子量: 400.903
• InChiKey: FVEOSPDAZDHAHF-YYLIZZNMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.12
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  124
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  左旋多巴 在 盐酸 、 氯化亚砜 、 1-羟基苯并三唑 、 1,2-二氯乙烷 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-cyclohexyl-1-[(S)-2-(3,4-dihydroxyphenyl)-1-methoxycarbonylethyl-carbamoyl]-ethylammonium chloride
  参考文献：
  名称：

  Design, synthesis and biological evaluation of peptide derivatives of l-dopa as anti-parkinsonian agents

  摘要：

  A series of dipeptide derivatives of L-dopa were synthesized and investigated for their pharmacological activity using the unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat as an experimental model of Parkinson's disease. Among them, (S)-isopropyl 2-(2-amino-2-methylpropanamido)-3-(3,4-dihydroxyphenyl) propanoate (4g) was found to be the most active compound, with 106% AUC activity and 149% peak activity of L-dopa after oral administration. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.007

文献信息

• WO2007/91018
  申请人：——

  公开号：——

  公开（公告）日：——
• EP1981839A1
  申请人：——

  公开号：EP1981839A1

  公开（公告）日：2008-10-22
• Non-Natural Amino Acid Derivatives
  申请人：Hobbs Christopher

  公开号：US20090036525A1

  公开（公告）日：2009-02-05

  Compounds of formula (I) have activity in alleviating the effects of impaired dopaminergic signaling, for example in the treatment of Parkinsons Disease: wherein: R 1 is a carboxyl, carboxyl ester, or carboxamide group; R 2 and R 3 are independently hydrogen, or a group —C(═O)R 6 or —C(═O)OR 6 wherein R 6 is C 1 -C 6 alkyl, or a group —CH 2 Q wherein Q is an optionally substituted monocyclic cycloalkyl or heterocyclyl ring of 3 to 6 ring atoms; R 7 is (i) optionally substituted phenyl or monocyclic heteroaryl, or (ii) a radical of formula —CHR 4 R 5 ; R 4 is (a) optionally substituted C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 2 -C 4 alkenyl, C 2 -C 4 alkenyloxy, or C 2 -C 4 alkynyl, or (b) —CH 2 XCH 3 , —CH 2 CH 2 XCH 3 , or —CH 2 XCH 2 CH 3 , wherein X is —O—, S, or —NR 7 wherein R 7 is hydrogen, methyl or ethyl; or —CH 2 Q or CH 2 OQ wherein Q is as defined in relation to R 6 ; and R 5 is hydrogen, methyl, ethyl, or methyl substituted by 1, 2 or 3 fluoro atoms; or R 4 and R 5 taken together with the carbon atom to which they are attached form an optionally substituted carbocyclic or heterocyclic ring of 3 to 6 ring atoms, optionally fused to a second, optionally substituted, carbocyclic or heterocyclic ring or 3 to 8 ring atoms; PROVIDED THAT the group R 7 is not the side chain of a natural amino acid.
• [EN] NON-NATURAL AMINO ACID DERIVATIVES<br/>[FR] DÉRIVÉS D'ACIDES AMINÉS NON NATURELS
  申请人：PROXIMAGEN LTD

  公开号：WO2007091018A1

  公开（公告）日：2007-08-16

  [EN] Compounds of formula (I) have activity in alleviating the effects of impaired dopaminergic signaling, for example in the treatment of Parkinsons Disease; wherein: R₁ is a carboxyl, carboxyl ester, or carboxamide group; R₂ and R₃ are independently hydrogen, or a group -C(=O)R₆ or -C(=O)OR₆ wherein R₆ is C₁-C₆ alkyl, or a group - CH₂Q wherein Q is an optionally substituted monocyclic cycloalkyl or heterocyclyl ring of 3 to 6 ring atoms; R₇ is (i) optionally substituted phenyl or monocyclic heteroaryl, or (ii) a radical of formula -CHR₄Rs; R₄ is (a) optionally substituted C₁-C₄ alkyl, C₁-C₄ alkoxy, C₂-C₄ alkenyl, C₂-C₄ alkenyloxy, or C₂-C₄ alkynyl, or (b) -CH₂XCH₃, -CH₂CH₂XCH₃, or -CH₂XCH₂CH₃, wherein X is -O-, S, or -NR₇ wherein R₇ is hydrogen, methyl or ethyl; or -CH₂Q or CH₂OQ wherein Q is as defined in relation to R₆; and R₅ is hydrogen, methyl, ethyl, or methyl substituted by 1, 2 or 3 fluoro atoms; or R₄ and R₅ taken together with the carbon atom to which they are attached form an optionally substituted carbocyclic or heterocyclic ring of 3 to 6 ring atoms, optionally fused to a second, optionally substituted, carbocyclic or heterocyclic ring or 3 to 8 ring atoms; PROVIDED THAT the group R₇ is not the side chain of a natural amino acid.
  [FR] La présente invention concerne des composés de formule (I) présentant une activité d'atténuation des effets de la signalisation dopaminergique, par exemple, dans le traitement de la maladie de Parkinson. Dans cette formule, R₁ est un carboxyle, un ester carboxyle, ou un groupe carboxamide; R₂ et R₃ sont indépendamment hydrogène ou un groupe -C(=O)R₆ ou -C(=O)OR₆ dans lequel R₆ est C₁-C₆ alkyle, ou un groupe _{- CH2Q dans lequel Q est un cycloalkyle monocyclique éventuellement substitué ou un noyau hétérocyclyle de 3 à 6 atomes cycliques; R7 est (i) phényle éventuellement substitué ou hétéroaryle monocyclique, ou (ii) un radical de formule -CHR4R5; R4 est (a) C1-C4 alkyle éventuellement substitué, C1-C4 alcoxy, C2-C4 alcényle, C2-C4 alcényloxy, ou C2-C4 alcynyle, ou (b) -CH2XCH3, -CH2CH2XCH3, ou -CH2XCH2CH3, dans lequel X est -O-, S, ou -NR7 dans lequel R7 est hydrogène, méthyle, ou éthyle; ou -CH2Q or CH2OQ, dans lequel Q est défini en relation avec R6; et R5 est hydrogène, méthyle, éthyle, ou méthyle substitué par 1, 2, ou 3 atomes fluorés; ou R4 et R5 ensemble avec l'atome de carbone auquel ils sont liés forment un noyau carbocyclique ou hétérocyclique éventuellement substitué de 3 à 6 atomes cycliques; à condition que le groupe R7 ne soit pas une chaîne latérale d'un acide aminé naturel.}
• Design, synthesis and biological evaluation of peptide derivatives of l-dopa as anti-parkinsonian agents
  作者：Tao Zhou、Robert C. Hider、Peter Jenner、Bruce Campbell、Christopher J. Hobbs、Sarah Rose、Mark Jairaj、Kayhan A. Tayarani-Binazir、Alexander Syme

  DOI：10.1016/j.bmcl.2013.08.007

  日期：2013.10

  A series of dipeptide derivatives of L-dopa were synthesized and investigated for their pharmacological activity using the unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat as an experimental model of Parkinson's disease. Among them, (S)-isopropyl 2-(2-amino-2-methylpropanamido)-3-(3,4-dihydroxyphenyl) propanoate (4g) was found to be the most active compound, with 106% AUC activity and 149% peak activity of L-dopa after oral administration. (C) 2013 Elsevier Ltd. All rights reserved.