methyl 3-carbomethoxy-3-(3'-methoxyphenyl)amino-2-propenoate | 77474-14-7

• 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: methyl 3-carbomethoxy-3-(3'-methoxyphenyl)amino-2-propenoate
• 英文别名: dimethyl 2-((3-methoxyphenyl)amino)but-2-enedioate；Dimethyl 2-(3-methoxyanilino)but-2-enedioate
• CAS: 77474-14-7
• 化学式: C₁₃H₁₅NO₅
• 分子量: 265.266
• InChiKey: UNVGCSIAQWEGCC-UHFFFAOYSA-N

物化性质

• 沸点：
  390.6±42.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 3-carbomethoxy-3-(3'-methoxyphenyl)amino-2-propenoate 在 三甲基铝 作用下， 以 四氢呋喃 、 正庚烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.28h， 生成 N-(2-(1-benzylpiperidin-4-yl)ethyl)-7-methoxy-4-oxo-1,4-dihydroquinoline-2-carboxamide
  参考文献：
  名称：

  Neurogenic and neuroprotective donepezil-flavonoid hybrids with sigma-1 affinity and inhibition of key enzymes in Alzheimer's disease

  摘要：

  In this work we describe neurogenic and neuroprotective donepezil-flavonoid hybrids (DFHs), exhibiting nanomolar affinities for the sigma-1 receptor (sigma R-1) and inhibition of key enzymes in Alzheimer's disease (AD), such as acetylcholinesterase (AChE), 5-lipoxygenase (5-LOX), and monoamine oxidases (MAOs). In general, new compounds scavenge free radical species, are predicted to be brain-permeable, and protect neuronal cells against mitochondrial oxidative stress. N-(2-(1-Benzylpiperidin-4-yl)ethyl)-6,7-dimethoxy-4-oxo-4H-chromene-2-carboxamide (18) is highlighted due to its interesting biological profile in sigma R-1, AChE, 5-LOX, MAO-A and MAO-B. In phenotypic assays, it protects a neuronal cell line against mitochondrial oxidative stress and promotes maturation of neural stem cells into a neuronal phenotype, which could contribute to the reparation of neuronal tissues. Molecular modelling studies of 18 in AChE, 5-LOX and sigma R-1 revealed the main interactions with these proteins, which will be further exploited in the optimization of new, more efficient DFHs. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.07.026
• 作为产物：
  描述：

  间氨基苯甲醚 、 丁炔二酸二甲酯 以 甲醇 为溶剂， 以95%的产率得到methyl 3-carbomethoxy-3-(3'-methoxyphenyl)amino-2-propenoate
  参考文献：
  名称：

  2-（4-异丙基噻唑-2-基）-7-甲氧基-8-甲基喹啉-4-醇的合成; Simeprevir合成的喹啉构件

  摘要：

  献给我的朋友和令人钦佩的人在他90的一次是阿尔弗雷德·贝德博士日生日（SR）。 抽象 描述了两种合成方法来合成西美普韦的非手性喹啉片段。两种方法都基于4-羟基-7-甲氧基-8-甲基喹啉-2-羧酸甲酯的合成，其4-羟基的保护以及噻唑环在2-位的酯基的构建。最后一步是对4-羟基保护基进行酸脱保护。 描述了两种合成方法来合成西美普韦的非手性喹啉片段。两种方法都基于4-羟基-7-甲氧基-8-甲基喹啉-2-羧酸甲酯的合成，其4-羟基的保护以及噻唑环在2-位的酯基的构建。最后一步是对4-羟基保护基进行酸脱保护。

  DOI：

  10.1055/s-0033-1340679

文献信息

• Antagonists of melanin concentrating hormone effects on the melanin concentrating hormone receptor
  申请人：Lynch K. John

  公开号：US20050209274A1

  公开（公告）日：2005-09-22

  The present invention is directed to compounds of formula (I), which antagonize of the effects of melanin-concentrating hormone (MCH) through the melanin concentrating hormone receptor which is useful for the prevention or treatment of eating disorders, weight gain, obesity, abnormalities in reproduction and sexual behavior, thyroid hormone secretion, diuresis and water/electrolyte homeostasis, sensory processing, memory, sleeping, arousal, anxiety, depression, seizures, neurodegeneration and psychiatric disorders.

  本发明涉及式(I)的化合物，通过对抗黑素浓集激素（MCH）的作用，通过对抗黑素浓集激素受体，有助于预防或治疗进食障碍、体重增加、肥胖、生殖和性行为异常、甲状腺激素分泌、利尿和水/电解质稳态、感觉处理、记忆、睡眠、觉醒、焦虑、抑郁、癫痫、神经退行性疾病和精神障碍。
• Chemoselective Nitrosylation of Anilines and Alkynes via Fragmentary or Complete NO Incorporation
  作者：Jun Pan、Xinyao Li、Fengguirong Lin、Jianzhong Liu、Ning Jiao

  DOI：10.1016/j.chempr.2018.03.008

  日期：2018.6

  fragmentations via chemical-bond cleavage are involved in this cycloaddition reaction, it would change the assembly sequence and enable more product diversity. Here, we report a chemoselective nitrosylation of anilines and alkynes through fragmentary or complete NO radical incorporation. The formation of multiple C–N bonds, an unexpected C–N bond, and N=O bond cleavage make this fragmentary cycloaddition

  环加成反应已被广泛研究，并为合成环状化合物提供了有效的策略。传统上，反应伙伴被广泛地掺入环状产物中而不会断裂。从不同的角度来看，如果在这种环加成反应中涉及通过化学键裂解的某些片段化，它将改变组装顺序并实现更多的产物多样性。在这里，我们报告通过部分或完全的NO自由基结合苯胺和炔烃的化学选择性亚硝基化。多个C–N键，意外的C–N键和N = O键断裂的形成使该片段性环加成反应成为2,5,2-二氢恶唑，1 H -1,2,3-三唑2-氧化物的有效方法或喹喔啉N-氧化物。在露天，无金属和温和条件下的简便操作使该协议特别实用且有吸引力。还进行了一系列的机理研究和密度泛函理论计算，这有助于解释零碎或完整的NO掺入过程，拓宽了新反应发现的领域。
• A Synthesis of 4-Quinolone-3-carboxylic Acids via Pyrolysis of N-Aryldioxopyrrolines
  作者：Kunihiko Mohri、Akihiko Kanie、Yoshie Horiguchi、Kimiaki Isobe

  DOI：10.3987/com-99-8629

  日期：——

  A synthesis of 4-quinolone-3-carboxylic acids (8) was achieved by pyrolysis of 4,5-dimethoxycarbonyl-1-aryl-1H-pyrrole-2,3-diones (3) followed by selective demethoxycarbonylation of the resulting 2,3-dimethoxycarbonyl-4-quinolones (4) in excellent overall yields.
• Discovery of a Potent and Selective Noncovalent Linear Inhibitor of the Hepatitis C Virus NS3 Protease (BI 201335)
  作者：Montse Llinàs-Brunet、Murray D. Bailey、Nathalie Goudreau、Punit K. Bhardwaj、Josée Bordeleau、Michael Bös、Yves Bousquet、Michael G. Cordingley、Jiamin Duan、Pat Forgione、Michel Garneau、Elise Ghiro、Vida Gorys、Sylvie Goulet、Ted Halmos、Stephen H. Kawai、Julie Naud、Marc-André Poupart、Peter W. White

  DOI：10.1021/jm100690x

  日期：2010.9.9

  C-Terminal carboxylic acid containing inhibitors of the NS3 protease are reported. A novel series of linear tripeptide inhibitors that are very potent and selective against the NS3 protease are described. A substantial contribution to the potency of these linear inhibitors arises from the introduction of a C8 substituent on the B-ring of the quinoline moiety found on the P2 of these inhibitors. The introduction of a CS methyl group results not only in a modest increase in the cell-based potency of these inhibitors but more importantly in a much better pharmacokinetic profile in rats as well. Exploration of C8-substitutions led to the identification of the bromo derivative as the best group at this position, resulting in a significant increase in the cell-based potency of this class of inhibitors. Structure activity studies on the C8-bromo derivatives ultimately led to the discovery of clinical candidate 29 (BI 201335), a very potent and selective inhibitor of genotypel NS3 protease with a promising PK profile in rats.