2-氨基-6-乙氧基苯甲腈 | 123241-42-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 2-氨基-6-乙氧基苯甲腈
• 英文名称: 2-amino-6-ethoxybenzonitrile
• 英文别名: CHIR166206；2-ethoxy-6-amino-benzonitrile；2-Aethoxy-6-amino-benzonitril；3-Amino-2-cyan-phenetol
• CAS: 123241-42-9
• 化学式: C₉H₁₀N₂O
• 分子量: 162.191
• InChiKey: OREORIYCUIWBGD-UHFFFAOYSA-N

物化性质

• 沸点：
  346.8±27.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氨基-6-乙氧基苯甲腈 在 sodium hydroxide 作用下， 生成 2-amino-6-ethoxybenzamide
  参考文献：
  名称：

  Friedlaender, Chemische Berichte, 1916, vol. 49, p. 965

  摘要：

  DOI：
• 作为产物：
  描述：

  2-ethoxy-6-nitro-benzonitrile 在 palladium on activated charcoal 环己烯 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以62%的产率得到2-氨基-6-乙氧基苯甲腈
  参考文献：
  名称：

  5-取代的2,4-二氨基喹唑啉的抗叶酸和抗菌活性。

  摘要：

  合成了一系列5-取代的2,4-二氨基喹唑啉（3），并从细菌和哺乳动物来源评估了它们作为二氢叶酸还原酶（DHFR）的抑制剂。最好的化合物（例如53种）对大肠杆菌DHFR表现出良好的活性，但对细菌的选择性没有比哺乳动物酶高的选择性。抑制酶的构效关系似乎很复杂，不宜进行简单分析。提出了一个假设来解释观察到的定性结构-活性关系。该化合物对体外完整细菌细胞生长的抑制活性与抑制分离的细菌酶的抑制活性非常相似，这表明它们的抗叶酸作用是其抗菌作用的原因。

  DOI：

  10.1021/jm00163a067

文献信息

• The Chemical Development of CHIR-258
  作者：Shuguang Zhu、Minna Zheng、Brian Diaz、Arthur Yeung、Li Jin、Gabriel Galvin、Xiao Shang、Shaopei Cai、Eric Harwood、David Ryckman

  DOI：10.2533/chimia.2006.584

  日期：——

  This paper is a case history of the early stage chemical development of CHIR-258 (4-amino-5-fluoro-3-[6(4-methyl-1-piperazinyl)-1H-benzimidazol-2-yl]-2(1H)-quinolinone, DL-lactate salt), a vascular endothelial growth factor (VEGF) kinase inhibitor for treatment of solid and hematologic cancers. The article covers various aspects of work in chemical development. In particular we discuss evaluation of the medicinal chemistry route, scale-up, salt preparation, process impurities, in-process control (IPC) method development, supply route development, technology transfer to contract manufacturing organization (CMO) and pilot plant production. Some interesting points regarding regulatory requirement for chemical development are also discussed.

  这篇论文是关于CHIR-258（4-氨基-5-氟-3-[6(4-甲基-1-哌嗪基)-1H-苯并咪唑-2-基]-2(1H)-喹啉酮，DL-乳酸盐）的早期化学开发案例。CHIR-258是一种血管内皮生长因子（VEGF）激酶抑制剂，用于治疗实体和血液系统癌症。文章涵盖了化学开发工作的各个方面。特别讨论了药物化学路线的评估、放大生产、盐制备、工艺杂质、过程控制方法的开发、供应途径的开发、技术转移给合同制造组织（CMO）以及中试生产。还讨论了化学开发的监管要求的一些有趣点。
• MODULATION OF CHEMOSENSORY RECEPTORS AND LIGANDS ASSOCIATED THEREWITH
  申请人：Tachdjian Catherine

  公开号：US20110224155A1

  公开（公告）日：2011-09-15

  The present invention includes methods for identifying modifiers of chemosensory receptors and their ligands, e.g., by determining whether a test entity is suitable to interact with one or more interacting sites within the Venus flytrap domains of the chemosensory receptors, and modifiers capable of modulating chemosensory receptors and their ligands. The present invention also includes modifiers of chemosensory receptors and their ligands having Formula (I), its subgenus, and specific compounds. Furthermore, the present invention includes ingestible compositions comprising the modifiers of chemosensory receptors and their ligands and methods of using the modifiers of chemosensory receptors and their ligands to enhance the sweet taste of an ingestible composition or treat a condition associated with a chemosensory receptor. In addition, the present invention include processes for preparing the modifiers of chemosensory receptors and their ligands.

  本发明包括识别化学感受受体及其配体的修饰剂的方法，例如通过确定测试实体是否适合与化学感受受体的捕蝇草结构域中的一个或多个相互作用位点发生相互作用，并且能够调节化学感受受体及其配体的修饰剂。本发明还包括化学感受受体及其配体的修饰剂，其具有式（I）、其亚属和具体化合物。此外，本发明还包括包含化学感受受体及其配体的修饰剂的可食用组合物以及使用化学感受受体及其配体的修饰剂增强可食用组合物的甜味或治疗与化学感受受体相关的疾病的方法。此外，本发明还包括制备化学感受受体及其配体的修饰剂的过程。
• Modulation of chemosensory receptors and ligands associated
  申请人：Senomyx, Inc.

  公开号：EP2568287A2

  公开（公告）日：2013-03-13

  The present invention includes methods for identifying modifiers of chemosensory receptors and their ligands, e.g., by determining whether a test entity is suitable to interact with one or more interacting sites within the Venus flytrap domains of the chemosensory receptors, and modifiers capable of modulating chemosensory receptors and their ligands. The present invention also includes modifiers of chemosensory receptors and their ligands having Formula (I), its subgenus, and specific compounds. Furthermore, the present invention includes ingestible compositions comprising the modifiers of chemosensory receptors and their ligands and methods of using the modifiers of chemosensory receptors and their ligands to enhance the sweet taste of an ingestible composition or treat a condition associated with a chemosensory receptor. In addition, the present invention includes processes for preparing the modifiers of chemosensory receptors and their ligands.

  本发明包括鉴定化感受体及其配体的修饰剂的方法，例如，通过确定试验实体是否适合与化感受体金星捕蝇草结构域内的一个或多个相互作用位点相互作用，以及能够修饰化感受体及其配体的修饰剂。本发明还包括具有式（I）、其亚属和特定化合物的化感受体及其配体的调节剂。此外，本发明还包括包含化感受体修饰剂及其配体的可食用组合物，以及使用化感受体修饰剂及其配体提高可食用组合物甜味或治疗与化感受体相关疾病的方法。此外，本发明还包括制备化感受体修饰剂及其配体的工艺。
• Synthesis and Biological Evaluation of Novel 2,4-Diaminoquinazoline Derivatives as <i>SMN2</i> Promoter Activators for the Potential Treatment of Spinal Muscular Atrophy
  作者：John Thurmond、Matthew E. R. Butchbach、Marty Palomo、Brian Pease、Munagala Rao、Louis Bedell、Monica Keyvan、Grace Pai、Rama Mishra、Magnus Haraldsson、Thorkell Andresson、Gisli Bragason、Margret Thosteinsdottir、Jon Mar Bjornsson、Daniel D. Coovert、Arthur H. M. Burghes、Mark E. Gurney、Jasbir Singh

  DOI：10.1021/jm061475p

  日期：2008.2.1

  Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord that is caused by deletion and/or mutation of the survival motor neuron gene (SMN1). Adjacent to SMN1 are a variable number of copies of the SMN2 gene. The two genes essentially differ by a single nucleotide, which causes the majority of the RNA transcripts from SMN2 to lack exon 7. Although both SMN1 and SMN2 encode the same Smn protein amino acid sequence, the loss of SMN1 and incorrect splicing of SMN2 have the consequence that Smn protein levels are insufficient for the survival of motor neurons. The therapeutic goal of our medicinal chemistry effort was to identify small-molecule activators of the SMN2 promoter that, by up-regulating gene transcription, would produce greater quantities of full-length Smn protein. Our initial medicinal chemistry effort explored a series of C5 substituted benzyl ether based 2,4-diaminoquinazoline derivatives that were found to be potent activators of the SMN2 promoter; however, inhibition of DHFR was shown to be an off-target activity that was linked to ATP depletion. We used a structure-guided approach to overcome DHFR inhibition while retaining SMN2 promoter activation. A lead compound 11a was identified as having high potency (EC50 = 4 nM) and 2.3-fold induction of the SMN2 promoter. Compound Ila possessed desirable pharmaceutical properties, including excellent brain exposure and long brain half-life following oral dosing to mice. The piperidine compound Ila up-regulated expression of the mouse SMN gene in NSC-34 cells, a mouse motor neuron hybrid cell line. In type I SMA patient fibroblasts, compound Ila induced Smn in a dose-dependent manner when analyzed by immuno-blotting and increased the number of intranuclear particles called gems. The compound restored gems numbers in type I SMA patient fibroblasts to levels near unaffected genetic carriers of SMA.
• Modulation of chemosensory receptors and ligands associated therewith
  申请人：Senomyx, Inc.

  公开号：EP2573559B1

  公开（公告）日：2019-03-13