2(R,S)-{2-[(1H-indole-2-carbonyl)-amino]-benzoylamino}-3-phenyl-propionic acid ethyl ester | 620167-32-0

• 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)-{2-[(1H-indole-2-carbonyl)-amino]-benzoylamino}-3-phenyl-propionic acid ethyl ester
• 英文别名: 2(R,S)-{2-[(1H-indol-2-carbonyl)amino]benzoylamino}-3-phenyl-propionic acid ethyl ester；ethyl 2-[[2-(1H-indole-2-carbonylamino)benzoyl]amino]-3-phenylpropanoate
• CAS: 620167-32-0
• 化学式: C₂₇H₂₅N₃O₄
• 分子量: 455.513
• InChiKey: BZHUCSYAEOOMGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  100
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2(R,S)-{2-[(1H-indole-2-carbonyl)-amino]-benzoylamino}-3-phenyl-propionic acid ethyl ester 在 lithium hydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以85%的产率得到VL-0395
  参考文献：
  名称：

  [EN] ANTHRANYL DERIVATIVES HAVING AN ANTICHOLECYSTOKININ ACTIVITY (ANTI-CCK-1), A PROCESS FOR THEIR PREPARATION, AND PHARMACEUTICAL USE THEREOF
  [FR] DERIVES D'ANTHRANYLE AYANT UNE ACTIVITE ANTICHOLECYSTOKININE (ANTI-CCK-1), LEUR PROCEDE DE PREPARATION ET LEUR UTILISATION PHARMACEUTIQUE

  摘要：

  具有抗CCK活性的Anthranylic化合物的一般式（I），其中，n是介于0和7之间的整数；R1独立地选择自群体（II），其中X1独立地选择自S、O、NR2和X2选择自：H、C1-C4烷基、F、Cl、CF3、OCH3、OC2H5、CN的群体；R2选择自H或CH3；R3选择自H、CH3、F、Cl、CF3、OCH3；R4选择自群体：H、-S-（CH2）m-R5、-SO2-（CH2）m-R5（n不等于0）、支链烷基、环烷基、环烯基、1或2-金刚烷基、可选取代的苯基；R5选择自群体：H、线性或支链烷基、环烷基、1或2-金刚烷基、适当取代的苯基。

  公开号：

  WO2004013087A1
• 作为产物：
  描述：

  靛红酸酐 在 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 4.0h， 生成 2(R,S)-{2-[(1H-indole-2-carbonyl)-amino]-benzoylamino}-3-phenyl-propionic acid ethyl ester
  参考文献：
  名称：

  Anthranilic acid derivatives: a new class of non-peptide CCK1 receptor antagonists

  摘要：

  Having successfully obtained new CCK1 ligands holding appropriate groups on the anthranilic acid dimer used as molecular scaffold we were interested in increasing their micromolar affinity for the CCK1 receptors by modifying the spatial relationship of the main pharmacophoric groups. Since, we have proposed simplified analogues reducing the anthranilic acid dimer to a monomer. In this stage of our research program we have prepared and tested on CCK receptors a series of N-substituted anthranilic acid derivatives keeping a Phe residue at the C-terminal site. The indole-2-carbonyl group imparts the best CCK1 receptor binding affinity (compound 1: IC50 = 197.5 nM) while a sharp decrease in binding affinity is observed for the other indole containing derivatives. Moreover, in order to support the different binding behaviour observed for the synthesized compounds, a conformational investigation was carried out. Finally, on the basis of the main pharmacophoric groups of the obtained new lead compound (1) (coded VL-0395) a receptor binding hypothesis has been provided. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00475-3

文献信息

• [EN] ANTHRANYL DERIVATIVES HAVING AN ANTICHOLECYSTOKININ ACTIVITY (ANTI-CCK-1), A PROCESS FOR THEIR PREPARATION, AND PHARMACEUTICAL USE THEREOF<br/>[FR] DERIVES D'ANTHRANYLE AYANT UNE ACTIVITE ANTICHOLECYSTOKININE (ANTI-CCK-1), LEUR PROCEDE DE PREPARATION ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：ROTTA RESEARCH LAB

  公开号：WO2004013087A1

  公开（公告）日：2004-02-12

  Anthranylic compounds having anti-CCK activity of general formula (I) in which, n is a whole number lying between 0 and 7; R1 is chosen independently from the groups (II), in which X1 is chosen independently from, S, O, NR2 and X2 is a group chosen from: H, C1-C4 alkyl, F, Cl, CF3, OCH3, OC2H5, CN; R2 is chosen from H or CH3; R3 is chosen from H, CH3, F, Cl, CF3, OCH3; R4 is chosen from the groups: H, -S-(CH2)m-R5, -SO2- (CH2)m-R5 (n different from 0), a branched alkyl group, a cyclo alkyl, a cyclo alkenyl, the group 1 or 2 adamantile, a phenyl group optionally substituted; R5 is chosen from the groups: H, linear or branched alkyl, cyclo alkyl, the group 1 or 2 adamantile, a suitably substituted phenyl group.

  具有抗CCK活性的Anthranylic化合物的一般式（I），其中，n是介于0和7之间的整数；R1独立地选择自群体（II），其中X1独立地选择自S、O、NR2和X2选择自：H、C1-C4烷基、F、Cl、CF3、OCH3、OC2H5、CN的群体；R2选择自H或CH3；R3选择自H、CH3、F、Cl、CF3、OCH3；R4选择自群体：H、-S-（CH2）m-R5、-SO2-（CH2）m-R5（n不等于0）、支链烷基、环烷基、环烯基、1或2-金刚烷基、可选取代的苯基；R5选择自群体：H、线性或支链烷基、环烷基、1或2-金刚烷基、适当取代的苯基。
• Anthranilic acid based CCK1 receptor antagonists: Blocking the receptor with the same ‘words’ of the endogenous ligand
  作者：Lucia Lassiani、Michela V. Pavan、Federico Berti、George Kokotos、Theodoros Markidis、Laura Mennuni、Francesco Makovec、Antonio Varnavas

  DOI：10.1016/j.bmc.2009.02.012

  日期：2009.3

  The anthranilic acid diamides represent the more recent class of nonpeptide CCK1 receptor antagonists. This class is characterized by the presence of anthranilic acid, used as a molecular scaffold, and two pharmacophores selected from the C-terminal tetrapeptide of CCK. The lead compound coded VL-0395, endowed with sub-micromolar affinity towards CCK1 receptors, was characterized by the presence of Phe and 2-indole moiety at the C- and N-termini of anthranilic acid, respectively. Herein we describe the first step of the anthranilic acid C- terminal optimization using, instead of Phe, aminoacids belonging to the primary structure of CCK-8 and other not coded residues. Thus we demonstrate that the CCK1 receptor affinity depends on the nature of the aminoacidic side chain as well as that the free carboxy group of the alpha-aminoacids is crucial for the binding. The R enantiomers of the most active compounds represent the eutomers of this class of antagonists confirming thus the stereo preference of the receptor. Moreover this SAR study demonstrates that the receptor binding pocket, that host the aminoacidic side chain, results much more tolerant respect to that accommodating the indole ring. As a result, an appropriate variation of the aminoacidic side chain could provide a better CCK1 receptor affinity diorthosis. (C) 2009 Elsevier Ltd. All rights reserved.
• Anthranilic acid derivatives: a new class of non-peptide CCK1 receptor antagonists
  作者：Antonio Varnavas、Lucia Lassiani、Valentina Valenta、Federico Berti、Laura Mennuni、Francesco Makovec

  DOI：10.1016/s0968-0896(02)00475-3

  日期：2003.3

  Having successfully obtained new CCK1 ligands holding appropriate groups on the anthranilic acid dimer used as molecular scaffold we were interested in increasing their micromolar affinity for the CCK1 receptors by modifying the spatial relationship of the main pharmacophoric groups. Since, we have proposed simplified analogues reducing the anthranilic acid dimer to a monomer. In this stage of our research program we have prepared and tested on CCK receptors a series of N-substituted anthranilic acid derivatives keeping a Phe residue at the C-terminal site. The indole-2-carbonyl group imparts the best CCK1 receptor binding affinity (compound 1: IC50 = 197.5 nM) while a sharp decrease in binding affinity is observed for the other indole containing derivatives. Moreover, in order to support the different binding behaviour observed for the synthesized compounds, a conformational investigation was carried out. Finally, on the basis of the main pharmacophoric groups of the obtained new lead compound (1) (coded VL-0395) a receptor binding hypothesis has been provided. (C) 2002 Elsevier Science Ltd. All rights reserved.