N-chloroacetyl p-aminomethylbenzoic acid methyl ester | 379255-44-4

• 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-chloroacetyl p-aminomethylbenzoic acid methyl ester
• 英文别名: 4-[(2-Chloro-acetylamino)-methyl]-benzoic acid methyl ester；methyl 4-[[(2-chloroacetyl)amino]methyl]benzoate
• CAS: 379255-44-4
• 化学式: C₁₁H₁₂ClNO₃
• mdl: MFCD03147364
• 分子量: 241.674
• InChiKey: MSDHDGHQLVRHJA-UHFFFAOYSA-N

物化性质

• 沸点：
  444.3±40.0 °C(Predicted)
• 密度：
  1.245±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-chloroacetyl p-aminomethylbenzoic acid methyl ester 在 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 18.0h， 以58%的产率得到N-iodoacetyl p-aminomethylbenzoic acid methyl ester
  参考文献：
  名称：

  Introduction of Peripheral Carboxylates to Decrease the Charge on Tm³⁺ DOTAM-Alkyl Complexes: Implications for Detection Sensitivity and in Vivo Toxicity of PARACEST MRI Contrast Agents

  摘要：

  A series of structurally modified Tm3+ DOTAM-alkyl complexes as potential PARACEST MRI contrast agents has been synthesized with the aim to decrease the overall positive charge associated with these molecules and increase their biocompatibility. Two types of structural modification have been performed, an introduction of terminal carboxylate arms to the alkyl side chains and a conjugation of one of the alkyl side chains with aspartic acid. Detailed evaluation of the magnetic resonance imaging chemical exchange contrast associated with the structurally modified contrast agents has been performed. In contrast to the acutely toxic Tm3+ DOTAM-alkyl complexes, the structurally modified compounds were found to be tolerated well during in vivo MRI studies in mice; however, only the aspartic acid modified chelates produced an amide proton-based PARACEST signal.

  DOI：

  10.1021/acs.jmedchem.5b00621
• 作为产物：
  描述：

  methyl 3-amino-3-methylbutanoate hydrochloride 、 氯乙酰氯 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以206 mg的产率得到N-chloroacetyl p-aminomethylbenzoic acid methyl ester
  参考文献：
  名称：

  Introduction of Peripheral Carboxylates to Decrease the Charge on Tm³⁺ DOTAM-Alkyl Complexes: Implications for Detection Sensitivity and in Vivo Toxicity of PARACEST MRI Contrast Agents

  摘要：

  A series of structurally modified Tm3+ DOTAM-alkyl complexes as potential PARACEST MRI contrast agents has been synthesized with the aim to decrease the overall positive charge associated with these molecules and increase their biocompatibility. Two types of structural modification have been performed, an introduction of terminal carboxylate arms to the alkyl side chains and a conjugation of one of the alkyl side chains with aspartic acid. Detailed evaluation of the magnetic resonance imaging chemical exchange contrast associated with the structurally modified contrast agents has been performed. In contrast to the acutely toxic Tm3+ DOTAM-alkyl complexes, the structurally modified compounds were found to be tolerated well during in vivo MRI studies in mice; however, only the aspartic acid modified chelates produced an amide proton-based PARACEST signal.

  DOI：

  10.1021/acs.jmedchem.5b00621

文献信息

• Novel Selective IDO1 Inhibitors with Isoxazolo[5,4-d]pyrimidin-4(5H)-one Scaffold
  作者：Ana Dolšak、Tomaž Bratkovič、Larisa Mlinarič、Eva Ogorevc、Urban Švajger、Stanislav Gobec、Matej Sova

  DOI：10.3390/ph14030265

  日期：——

  Here we present the synthesis of a series of IDO1 inhibitors with the novel isoxazolo[5,4-d]pyrimidin-4(5H)-one scaffold. A focused library was prepared using a 6- or 7-step synthetic procedure to allow a systematic investigation of the structure-activity relationships of the described scaffold. Chemistry-driven modifications lead us to the discovery of our best-in-class inhibitors possessing p-trifluoromethyl

  吲哚胺2，3-二加氧酶1（IDO1）是几种病理状况，尤其是癌症的免疫调节中的有希望的目标。在这里，我们目前与新型异恶唑并[5,4 - d ]嘧啶-4（5 H）-一个支架的一系列IDO1抑制剂的合成。使用6步或7步合成程序制备了一个有针对性的文库，以系统地研究所述支架的构效关系。化学驱动的修改导致我们我们具有最佳的类抑制剂的发现p三氟甲基（23），p -环己基（32），或p甲氧基羰基（20，39）IC 50值在低微摩尔范围内的取代苯胺部分。除hIDO1以外，还测试了化合物对吲哚胺2,3-双加氧酶2和色氨酸双加氧酶的抑制作用，发现它们对hIDO1具有选择性。因此，我们的结果证明了对IDO1选择性异恶唑并[5,4- d ]嘧啶4（5 H）-one抑制剂的成功研究，它定义了一种有前途的化学探针，并带有用于进一步开发强效小分子免疫调节剂的新型支架。