2-acetylamino-2-(4-phenyl-butyl)malonic acid diethyl ester | 80887-21-4

• 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-acetylamino-2-(4-phenyl-butyl)malonic acid diethyl ester
• 英文别名: diethyl (4-phenylbutyl)acetamidomalonate；Diethyl 2-acetamido-2-(4-phenylbutyl)propanedioate
• CAS: 80887-21-4
• 化学式: C₁₉H₂₇NO₅
• 分子量: 349.427
• InChiKey: GJFTXQMURLQVEQ-UHFFFAOYSA-N

物化性质

• 熔点：
  56-57 °C(Solv: ethyl acetate (141-78-6); hexane (110-54-3))
• 沸点：
  504.5±50.0 °C(Predicted)
• 密度：
  1.103±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-acetylamino-2-(4-phenyl-butyl)malonic acid diethyl ester 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 3.0h， 以67%的产率得到2-(RS)-amino-6-phenylhexanoic acid hydrochloride
  参考文献：
  名称：

  [EN] NEOSEPTINS: SMALL MOLECULE ADJUVANTS
  [FR] NÉOSEPTINES : PETITS ADJUVANTS MOLÉCULAIRES

  摘要：

  揭示了一种MD-2:TLR4复合物激动剂化合物，其结构对应于所定义的公式（I）。还公开了其制备和使用方法，以及含有该化合物的药物组合物。

  公开号：

  WO2014131023A1
• 作为产物：
  描述：

  4-苯基丁醇 在 咪唑 、 碘 、 sodium hydride 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 、 mineral oil 为溶剂， 反应 17.25h， 生成 2-acetylamino-2-(4-phenyl-butyl)malonic acid diethyl ester
  参考文献：
  名称：

  [EN] NEOSEPTINS: SMALL MOLECULE ADJUVANTS
  [FR] NÉOSEPTINES : PETITS ADJUVANTS MOLÉCULAIRES

  摘要：

  揭示了一种MD-2:TLR4复合物激动剂化合物，其结构对应于所定义的公式（I）。还公开了其制备和使用方法，以及含有该化合物的药物组合物。

  公开号：

  WO2014131023A1

文献信息

• [EN] NEOSEPTINS: SMALL MOLECULE ADJUVANTS<br/>[FR] NÉOSEPTINES : PETITS ADJUVANTS MOLÉCULAIRES
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2014131023A1

  公开（公告）日：2014-08-28

  A MD-2:TLR4 complex agonist compound is disclosed whose structure corresponds to Formula (I), as defined within. Also disclosed are a method of its preparation and use, as well as a pharmaceutical composition containing the same.

  揭示了一种MD-2:TLR4复合物激动剂化合物，其结构对应于所定义的公式（I）。还公开了其制备和使用方法，以及含有该化合物的药物组合物。
• NEOSEPTINS: SMALL MOLECULE ADJUVANTS
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：US20160000907A1

  公开（公告）日：2016-01-07

  A MD-2:TLR4 complex agonist compound is disclosed whose structure corresponds to Formula (I), as defined within. Also disclosed are a method of its preparation and use, as well as a pharmaceutical composition containing the same.

  本文披露了一种结构符合公式（I）定义的MD-2：TLR4复合激动剂化合物。同时还披露了其制备和使用方法，以及含有该化合物的药物组合物。
• Synthesis and biological evaluation of cholecystokinin analogs in which the Asp-Phe-NH2 moiety has been replaced by a 3-amino-7-phenylheptanoic acid or a 3-amino-6-(phenyloxy)hexanoic acid
  作者：Muriel Amblard、Marc Rodriguez、Marie Francoise Lignon、Marie Christine Galas、Nicole Bernad、Anne Marie Artis-Noel、Leticia Hauad、Jeanine Laur、Jean Christophe Califano

  DOI：10.1021/jm00072a024

  日期：1993.10

  Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester (JMV180), an analog of the C-terminal octapeptide of cholecystokinin (CCK-8), shows interesting biological activities behaving as an agonist at the high-affinity CCK binding sites and as an antagonist at the low-affinity CCK binding sites in rat pancreatic acini. Although we did not observe any major hydrolysis of the ester bond of Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester in our in vitro studies, we were aware of a possible and rapid cleavage of this ester bond during in vivo studies. To improve the stability of Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester, we decided to synthesize analogs in which the ester bond would be replaced by a carba (CH2-CH2) linkage. We synthesized the 3-amino-7-phenylheptanoic acid (beta-homo-Aph) with the R configuration in order to mimic the Asp-2-phenylethyl ester moiety and the 3-amino-6-(phenyloxy)hexanoic acid (H-beta-homo-App-OH), an analog of H-beta-homo-Aph-OH in which a methylene group has been replaced by an oxygen. (R)-beta-Homo-Aph and (R)-H-beta-homo-App-OH were introduced in the CCK-8 sequence to produce Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-(R)-beta-homo-Aph-OH and Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-(R)-beta-homo-App-OH. Both compounds were able to recognize the CCK receptor on rat pancreatic acini (IC50 = 12 +/- 8 nM and 13 +/- 5 nM, respectively), on brain membranes (IC50 = 32 +/- 2 nM and 57 +/- 5 nM, respectively), and on Jurkat T cells (IC50 = 75 +/- 15 nM and 65 +/- 21 nM, respectively). Like Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester, both compounds produced maximal stimulation of amylase secretion (EC50 = 6 +/- 2 nM and 4 +/- 2 nM, respectively) with no decrease of the secretion at high concentration indicating that these compounds probably act as agonists at the high-affinity peripheral CCK-receptor and as antagonists at the low-affinity CCK-receptor. Replacing the tryptophan by a D-tryptophan in such analogs produced full CCK-receptor antagonists. All these analogs might be more suitable for in vivo studies than Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester.
• US9649373B2
  申请人：——

  公开号：US9649373B2

  公开（公告）日：2017-05-16
• New Anthranilic Acid Based Antagonists with High Affinity and Selectivity for the Human Cholecystokinin Receptor 1 (hCCK₁-R)
  作者：Michela V. Pavan、Lucia Lassiani、Federico Berti、Giorgio Stefancich、Alessia Ciogli、Francesco Gasparrini、Laura Mennuni、Flora Ferrari、Chantal Escrieut、Esther Marco、Francesco Makovec、Daniel Fourmy、Antonio Varnavas

  DOI：10.1021/jm200438b

  日期：2011.8.25

  The anthranilic acid diamides represent the most recent class of nonpeptide CCK1 receptor (CCK1-R) antagonists. Herein we describe the second phase of the anthranilic acid C-terminal optimization using nonproteinogenic amino acids containing a phenyl ring in their side chain. The Homo-Phe derivative 2 (VL-0797) enhanced 12-fold the affinity for the rat CCK1-R affinity and 15-fold for the human CCK1-R relative to the reference compound 12 (VL-0395). The eutomer of 2 (6) exhibited a nanomolar range affinity toward the human CCK1-R and was at least 400-fold selective for the CCK1-R over the CCK2-R. Molecular docking in the modeled CCK1-R and its validation by site-directed mutagenesis experiments showed that the 6 binding site overlaps that occupied by the C-terminal bioactive region of the natural agonist CCK. Owing to their interesting properties, new compounds provided by this study represent a solid basis for further advances aimed at synthesis of clinically valuable CCK1-R antagonists.