2-(1-萘甲酰基)丙二腈 | 1236038-48-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 2-(1-萘甲酰基)丙二腈
• 英文名称: 2-(1-naphthoyl)Malononitrile
• 英文别名: 2-(naphthalene-1-carbonyl)propanedinitrile
• CAS: 1236038-48-4
• 化学式: C₁₄H₈N₂O
• 分子量: 220.23
• InChiKey: LJEFDGSTKLVSJB-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于氯仿、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  64.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1-萘甲酰基)丙二腈 在 三乙胺 作用下， 生成 1-(2-ethylphenyl)-3-(naphthalen-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (7)
  参考文献：
  名称：

  1,3-二取代-4-氨基吡唑并[3，4-d]嘧啶，一类新型的磷脂酶D抑制剂

  摘要：

  磷脂酶D酶裂解脂质底物以产生磷脂酸，磷脂酸是许多必需细胞分子的重要前体。磷脂酶D是调节癌细胞侵袭性的靶标。这项研究报告了基于1,3-二取代-4-氨基-吡唑并嘧啶核心结构的新型磷脂酶D抑制剂的合成。这些分子被合成并用于为纯化的细菌磷脂酶d的抑制，这是高度同源的人的PLD执行初步筛选1。最初用细菌磷脂酶D酶进行测试，然后用重组人PLD 1和PLD 2酶确认，此处显示的分子表现出对磷脂酶D活性的抑制作用（IC 50）在低纳摩尔至低微摩尔范围内，同时具有单体底物diC 4 PC和磷脂囊泡和胶束。数据强烈表明这些抑制分子直接阻断了酶/囊泡底物的结合。初步活性研究使用重组人磷脂酶Ds在体内细胞测定中测量了转磷脂酰化和头部裂解，表明在生理环境中这些有效的抑制性新分子在中低纳摩尔范围内具有抑制作用。

  DOI：

  10.1111/cbdd.12319
• 作为产物：
  描述：

  1-萘甲酸 在 草酰氯 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 2-(1-萘甲酰基)丙二腈
  参考文献：
  名称：

  Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii

  摘要：

  Toxoplasma gondii is sensitive to bulky pyrazolo [3,4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1). Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1). The potency of PP analogues in inhibiting CDPK1 enzyme activity in vitro (low nM IC50 values) and blocking parasite growth in host cell monolayers in vivo (low mu M EC50 values) were highly correlated and occurred in a CDPK1-specific manner. Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity. Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model. Collectively, the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis and perhaps related parasitic diseases.

  DOI：

  10.1021/jm4001314

文献信息

• [EN] COMPOSITIONS AND METHODS FOR TREATING TOXOPLASMOSIS. CRYPTOSPORIDIOSIS AND OTHER APICOMPLEXAN PROTOZOAN RELATED DISEASES<br/>[FR] COMPOSITIONS ET PROCÉDÉS POUR TRAITER LA TOXOPLASMOSE, LA CRYPTOSPORIDIOSE ET D'AUTRES MALADIES ASSOCIÉES AUX PROTOZOAIRES APICOMPLEXA
  申请人：UNIV WASHINGTON

  公开号：WO2011094628A1

  公开（公告）日：2011-08-04

  Compositions and methods for the treatment of toxoplasmosis-, caused by the infectious eukaryotic parasite Toxoplasma gondii (T, gondii) and for the treatment of ciyptosporidiosis, caused by the infectious eukaryotic parasites Cryptosporidium parvum (C parvuai) and Cnγtosporidium homimus (C. hominus) are described. In particular, the present disclosure is directed to compositions and methods for inhibiting either T. gondii calcium dependent protein kinases (TgCDPKs) or C. parvum and C. hominus calcium dependent protein kinases (CpDPKS) using pyrazolopyriinidine and/or imidazo[l,5-a]pyraziαe inhibitors, of the formula.(I), wherein the variables X. Y, Z, L. R1. and R3 are defined herein.

  本文描述了用于治疗由感染性真核寄生虫弓形虫（T. gondii）引起的弓形虫病和用于治疗由感染性真核寄生虫隐孢子虫（C. parvum）和人隐孢子虫（C. hominus）引起的隐孢子虫病的组合物和方法。具体而言，本公开涉及使用吡唑吡啶啉和/或咪唑[1,5-a]吡嗪类抑制剂来抑制T. gondii钙依赖蛋白激酶（TgCDPKs）或C. parvum和C. hominus钙依赖蛋白激酶（CpDPKS）的组合物和方法，其化学式为(I)，其中变量X、Y、Z、L、R1和R3在此处定义。
• Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii
  作者：Sebastian Lourido、Chao Zhang、Michael S. Lopez、Keliang Tang、Jennifer Barks、Qiuling Wang、Scott A. Wildman、Kevan M. Shokat、L. David Sibley

  DOI：10.1021/jm4001314

  日期：2013.4.11

  Toxoplasma gondii is sensitive to bulky pyrazolo [3,4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1). Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1). The potency of PP analogues in inhibiting CDPK1 enzyme activity in vitro (low nM IC50 values) and blocking parasite growth in host cell monolayers in vivo (low mu M EC50 values) were highly correlated and occurred in a CDPK1-specific manner. Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity. Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model. Collectively, the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis and perhaps related parasitic diseases.
• 1,3‐Disubstituted‐4‐Aminopyrazolo [3, 4‐d] Pyrimidines, a New Class of Potent Inhibitors for Phospholipase <scp>D</scp>
  作者：Aditya Kulkarni、Phong Quang、Victoriana Curry、Renee Keyes、Weihong Zhou、Hyejin Cho、Jonathan Baffoe、Béla Török、Kimberly Stieglitz

  DOI：10.1111/cbdd.12319

  日期：2014.9

  Phospholipase D enzymes cleave lipid substrates to produce phosphatidic acid, an important precursor for many essential cellular molecules. Phospholipase D is a target to modulate cancer‐cell invasiveness. This study reports synthesis of a new class of phospholipase D inhibitors based on 1,3‐disubstituted‐4‐amino‐pyrazolopyrimidine core structure. These molecules were synthesized and used to perform initial

  磷脂酶D酶裂解脂质底物以产生磷脂酸，磷脂酸是许多必需细胞分子的重要前体。磷脂酶D是调节癌细胞侵袭性的靶标。这项研究报告了基于1,3-二取代-4-氨基-吡唑并嘧啶核心结构的新型磷脂酶D抑制剂的合成。这些分子被合成并用于为纯化的细菌磷脂酶d的抑制，这是高度同源的人的PLD执行初步筛选1。最初用细菌磷脂酶D酶进行测试，然后用重组人PLD 1和PLD 2酶确认，此处显示的分子表现出对磷脂酶D活性的抑制作用（IC 50）在低纳摩尔至低微摩尔范围内，同时具有单体底物diC 4 PC和磷脂囊泡和胶束。数据强烈表明这些抑制分子直接阻断了酶/囊泡底物的结合。初步活性研究使用重组人磷脂酶Ds在体内细胞测定中测量了转磷脂酰化和头部裂解，表明在生理环境中这些有效的抑制性新分子在中低纳摩尔范围内具有抑制作用。