N-(3-toluoyl)aminoacetaldehyde dimethyl acetal | 133933-18-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-toluoyl)aminoacetaldehyde dimethyl acetal
• 英文别名: N-(2,2-dimethoxyethyl)-3-methylbenzamide
• CAS: 133933-18-3
• 化学式: C₁₂H₁₇NO₃
• mdl: MFCD17257385
• 分子量: 223.272
• InChiKey: BIIDXIQGMVZGKZ-UHFFFAOYSA-N

物化性质

• 沸点：
  356.3±42.0 °C(Predicted)
• 密度：
  1.069±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-toluoyl)aminoacetaldehyde dimethyl acetal 在 硫酸 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 168.0h， 生成 7-methyl-2-<(pivaloyloxy)methyl>isoquinolin-1-(2H)-one
  参考文献：
  名称：

  Folate analogs. 35. Synthesis and biological evaluation of 1-deaza, 3-deaza, and bridge-elongated analogs of N10-propargyl-5,8-dideazafolic acid

  摘要：

  Structural modifications at the pyrimidine ring and at the C-9,N-10-bridge region of the thymidylate synthase (TS) inhibitors N-10-propargyl-5,8-dideazafolate (1; PDDF; CB 3717), 2-desamino-N10-propargyl-5,8-dideazafolate (2, DPDDF), and 2-desamino-2-methyl-N-10-propargyl-5,8-dideazafolate (3, DMPDDF) have been carried out. Methods for the synthesis of 2-desamino-N-10-propargyl-1,5,8-trideazafolate (4), 2-desamino-2-methyl-N-10-propargyl-3,5,8-trideazafolate (5a), and 2-desamino-2-methyl-N10-propargyl-5,8-dideaza-1,2-dihydrofolate (6) have been developed. The bridge-extended analogues isohomo-PDDF (7) and isohomo-DMPDDF (8) contain an additional methylene group interposed between N-10 and the phenyl ring of 1 and 3, respectively. All new compounds were evaluated as inhibitors of TS and the growth of tumor cells in culture. Selected analogues were tested as substrates of folylpolyglutamate synthetase (FPGS) and striking differences in substrate activity were observed among these compounds, indicating that structural modifications at the pyrimidine ring of classical antifolates profoundly influence their polyglutamylation. Enzyme inhibition data established that both N1 and N3-H of the pyrimidine ring are essential for efficient binding of quinazoline-type antifolates to human TS.

  DOI：

  10.1021/jm00113a011
• 作为产物：
  描述：

  间甲基苯甲酸 在 氯化亚砜 、 potassium carbonate 作用下， 以 苯 为溶剂， 反应 18.0h， 生成 N-(3-toluoyl)aminoacetaldehyde dimethyl acetal
  参考文献：
  名称：

  Folate analogs. 35. Synthesis and biological evaluation of 1-deaza, 3-deaza, and bridge-elongated analogs of N10-propargyl-5,8-dideazafolic acid

  摘要：

  Structural modifications at the pyrimidine ring and at the C-9,N-10-bridge region of the thymidylate synthase (TS) inhibitors N-10-propargyl-5,8-dideazafolate (1; PDDF; CB 3717), 2-desamino-N10-propargyl-5,8-dideazafolate (2, DPDDF), and 2-desamino-2-methyl-N-10-propargyl-5,8-dideazafolate (3, DMPDDF) have been carried out. Methods for the synthesis of 2-desamino-N-10-propargyl-1,5,8-trideazafolate (4), 2-desamino-2-methyl-N-10-propargyl-3,5,8-trideazafolate (5a), and 2-desamino-2-methyl-N10-propargyl-5,8-dideaza-1,2-dihydrofolate (6) have been developed. The bridge-extended analogues isohomo-PDDF (7) and isohomo-DMPDDF (8) contain an additional methylene group interposed between N-10 and the phenyl ring of 1 and 3, respectively. All new compounds were evaluated as inhibitors of TS and the growth of tumor cells in culture. Selected analogues were tested as substrates of folylpolyglutamate synthetase (FPGS) and striking differences in substrate activity were observed among these compounds, indicating that structural modifications at the pyrimidine ring of classical antifolates profoundly influence their polyglutamylation. Enzyme inhibition data established that both N1 and N3-H of the pyrimidine ring are essential for efficient binding of quinazoline-type antifolates to human TS.

  DOI：

  10.1021/jm00113a011

文献信息

• [EN] CARBOXAMIDE COMPOUNDS AND THEIR USE AS ANTAGONISTS OF THE CHEMOKINE CCR2 RECEPTOR<br/>[FR] COMPOSÉS DE CARBOXYAMIDE ET LEUR UTILISATION COMME ANTAGONISTES DU RÉCEPTEUR CCR2DE LA CHIMIOKINE
  申请人：EPIX DELAWARE INC

  公开号：WO2009076404A1

  公开（公告）日：2009-06-18

  Chemokine receptor antagonists, in particular, compounds of Formula (I) that act as antagonists of the chemokine CCR2 receptor, including pharmaceutical compositions and uses thereof to treat or prevent diseases associated with monocyte accumulation, lymphocyte accumulation or leukocyte accumulation are described; wherein (B/A) is an optionally substituted fused aromatic or partially aromatic bicyclic ring containing at least one nitrogen atom.

  描述了特定的化学物质，即作为趋化因子CCR2受体拮抗剂的Formula (I)化合物，包括其药用组合物和用途，用于治疗或预防与单核细胞、淋巴细胞或白细胞聚积相关的疾病；其中(B/A)是一个可选择地取代的融合芳香或部分芳香的双环环，其中至少含有一个氮原子。
• Carboxamide Compounds and Their Use
  申请人：Ben-Zeev Efrat

  公开号：US20100331298A1

  公开（公告）日：2010-12-30

  Chemokine receptor antagonists, in particular, compounds of Formula (I) that act as antagonists of the chemokine CCR2 receptor, including pharmaceutical compositions and uses thereof to treat or prevent diseases associated with monocyte accumulation, lymphocyte accumulation or leukocyte accumulation are described herein.

  本文描述了化学因子受体拮抗剂，特别是式（I）化合物，其作为趋化因子CCR2受体的拮抗剂，包括制药组合物及其用于治疗或预防与单核细胞聚集、淋巴细胞聚集或白细胞聚集相关的疾病。
• Stereoselective Synthesis of 2‐Oxyenamides**
  作者：Sara‐Cathrin Krieg、Jennifer Grimmer、Annika Maria Pick、Harald Kelm、Martin Breugst、Georg Manolikakes

  DOI：10.1002/ejoc.202200772

  日期：2022.8.19

  An improved method for the stereoselective synthesis of (Z)-2-oxyneamides is described. This 2nd generation route is based on readily available aminoacetaldehyde dimethyl acetal as common building block for the preparation of various acylated and sulfonylated 2-oxyenamides. DFT calculations show a strong thermodynamic preference for the Z-oxyenamide products.

  描述了一种改进的 ( Z )-2-oxyneamides 立体选择性合成方法。该第 2代路线基于容易获得的氨基乙醛二甲基缩醛作为制备各种酰化和磺酰化 2-氧酰胺的常用构件。DFT 计算显示对 Z-氧酰胺产品具有强烈的热力学偏好。