amino-4-phenyl methyl malonate d'ethyle | 61881-50-3

• 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: amino-4-phenyl methyl malonate d'ethyle
• 英文别名: diethyl (4-aminophenyl)methylmalonate；2-(4-Aminophenyl)-2-methylmalonsaeure-diethylester；Diethyl-(4-aminophenyl)-methylmalonat；diethyl 2-(4-aminophenyl)-2-methylmalonate；diethyl 2-(4-aminophenyl)-2-methylpropanedioate
• CAS: 61881-50-3
• 化学式: C₁₄H₁₉NO₄
• 分子量: 265.309
• InChiKey: YZAHUPCNNKTQTC-UHFFFAOYSA-N

物化性质

• 沸点：
  374.3±32.0 °C(Predicted)
• 密度：
  1.146±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  amino-4-phenyl methyl malonate d'ethyle 在 盐酸 、 sodium hydroxide 、 四(三苯基膦)钯 、 sodium carbonate 、 sodium nitrite 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 生成 2-(4'-Trifluoromethyl-biphenyl-4-yl)-propionic acid
  参考文献：
  名称：

  Synthesis and Biological Activity of Flurbiprofen Analogues as Selective Inhibitors of β-Amyloid_1-42 Secretion

  摘要：

  Flurbiprofen, a nonsteroidal antiinflammatory drug (NSAID), has been recently described to selectively inhibit beta-amyloid(1-42) (A beta 42) secretion, the most toxic component of the senile plaques present in the brain of Alzheimer patients. The use of this NSAID in Alzheimer's disease (AD) is hampered by a significant gastrointestinal toxicity associated with cyclooxygenase (COX) inhibition. New flurbiprofen analogues were synthesized, with the aim of increasing A beta 42 inhibitory potency while removing anti-COX activity. In vitro ADME developability parameters were taken into account in order to identify optimized compounds at an early stage of the project. Appropriate substitution patterns at the alpha position of flurbiprofen allowed for the complete removal of anti-COX activity, while modifications at the terminal phenyl ring resulted in increased inhibitory potency on A beta 42 secretion. In rats, some of the compounds appeared to be well absorbed after oral administration and to penetrate into the central nervous system. Studies in a transgenic mice model of AD showed that selected compounds significantly decreased plasma A beta 42 concentrations. These new flurbiprofen analogues represent potential drug candidates to be developed for the treatment of AD.

  DOI：

  10.1021/jm0502541
• 作为产物：
  描述：

  甲基丙二酸二乙酯 在 palladium 10% on activated carbon 氢气 、 sodium hydride 作用下， 以 甲醇 、 二甲基亚砜 、 mineral oil 为溶剂， 20.0 ℃ 、200.0 kPa 条件下， 反应 17.5h， 生成 amino-4-phenyl methyl malonate d'ethyle
  参考文献：
  名称：

  TRICYCLIC PYRIDINE DERIVATIVES, MEDICAMENTS CONTAINING SUCH COMPOUNDS, THEIR USE AND PROCESS FOR THEIR PREPARATION

  摘要：

  本发明涉及由公式I定义的化合物 其中变量R1-R8定义如说明书中所述，具有宝贵的药理活性。特别是，这些化合物是胆固醇酯转移蛋白（CETP）的抑制剂，因此适合用于治疗和预防可以通过抑制该酶而影响的疾病。

  公开号：

  US20120046304A1

文献信息

• Inhibitors of protein kinases
  申请人：Zeitlmann Lutz

  公开号：US20110224225A1

  公开（公告）日：2011-09-15

  Compounds of general Formula (I): wherein R 1 , R 2 , R 3 , R a , A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and/or the glycogen synthase kinase 3 family and are useful in preventing and/or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.

  通用式(I)的化合物： 其中R1、R2、R3、Ra、A、B和x的定义如本文所述，是特定于细胞周期蛋白激酶家族和/或糖原合成酶激酶3家族的抑制剂，并且在预防和/或治疗任何类型的疼痛、炎症性疾病、癌症、免疫性疾病、增殖性疾病、传染病、心血管疾病、代谢性疾病、肾脏疾病、神经和神经精神疾病以及神经退行性疾病方面具有用处。
• Preparation and Biological Activity of 2-(4-(Thiazol-2-yl)phenyl)propionic Acid Derivatives Inhibiting Cyclooxygenase.
  作者：Youichiro NAITO、Tomokazu GOTO、Fumihiko AKAHOSHI、Shiniciro ONO、Haruko YOSHITOMI、Tadashi OKANO、Naoki SUGIYAMA、Shunichi ABE、Syuichi HANADA、Mitsuru HIRATA、Masahiro WATANABE、Chikara FUKAYA、Kazumasa YOKOYAMA、Toshio FUJITA

  DOI：10.1248/cpb.39.2323

  日期：——

  A series of 2-[4-(thiazol-2-yl)phenyl]propionic acids substituted at various positions were prepared by the reaction of diethyl 2-methyl-2-(4-thiocarbamoylphenyl)malonates with alpha-bromoaldehyde diethyl acetals or alpha-haloketones followed by hydrolysis of esters. The inhibition of prostaglandin H synthetase (cyclooxygenase) was assayed by use of an enzyme preparation from guinea pig polymorphonuclear

  通过使2-甲基-2-（4-硫代氨基甲酰基苯基）丙二酸二乙酯与α-溴醛二乙缩醛或α反应制备一系列在各个位置取代的2- [4-（噻唑-2-基）苯基]丙酸。 -卤代酮，然后酯水解。通过使用来自豚鼠多形核白细胞的酶制剂测定前列腺素H合成酶（环加氧酶）的抑制作用。这些化合物的结构活性关系的研究表明，苯环3位（R1）处的卤素和噻唑环4位（R2）和/或5位（R3）处的甲基被卤素取代是有利的抑制活性。在R2位带有大的烷基或极性官能团的化合物是弱抑制剂。测试了有效的环氧合酶抑制剂减轻角叉菜胶诱导的大鼠爪炎症的能力。这些衍生物由于对环加氧酶的强抑制作用而具有很强的抗炎活性，除了一些例外，包括那些在R1处带有硫代甲基的衍生物。
• Tricyclic pyridine derivatives, medicaments containing such compounds, their use and process for their preparation
  申请人：Wagner Holger

  公开号：US20130053404A1

  公开（公告）日：2013-02-28

  The present invention relates to compounds defined by formula I wherein the variables R 1 -R 8 are defined as in the description, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of cholesterol ester transfer protein (CETP) and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme.

  本发明涉及由式I定义的化合物，其中变量R1-R8如描述中所定义，具有有价值的药理活性。特别地，这些化合物是胆固醇酯转移蛋白（CETP）的抑制剂，因此适用于治疗和预防受该酶抑制影响的疾病。
• [EN] TRICYCLIC PYRIDINE DERIVATIVES, MEDICAMENTS CONTAINING SUCH COMPOUNDS, THEIR USE AND PROCESS FOR THEIR PREPARATION<br/>[FR] DÉRIVÉS DE PYRIDINE TRICYCLIQUE, MÉDICAMENTS CONTENANT DE TELS COMPOSÉS, LEUR UTILISATION ET L'UN DE LEURS PROCÉDÉS DE SYNTHÈSE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012110599A1

  公开（公告）日：2012-08-23

  The present invention relates to compounds defined by formula (I), wherein the variables R1-R8 are defined as in the description, possessing valuable pharmacological activity. Particularly, the compounds are inhibitors of cholesterol ester transfer protein (CETP) and thus are suitable for treatment and prevention of diseases which can be influenced by inhibition of this enzyme.

  本发明涉及由式（I）定义的化合物，其中变量R1-R8如描述中所定义，具有有价值的药理活性。特别地，这些化合物是胆固醇酯转移蛋白（CETP）的抑制剂，因此适用于治疗和预防受该酶抑制影响的疾病。
• Studies on the synthesis and analgesic and anti-inflammatory activities of 2-thiazolylamino- and 2-thiazolyloxy-arylacetic acid derivatives.
  作者：RYOZO MAEDA、EIICHI OHSUGI、TOSHIHIRO FUJIOKA、KATSUMI HIROSE

  DOI：10.1248/cpb.31.3424

  日期：——

  A series of 2-thiazolylamino-, 2-thiazolyloxy- and 2-thiazolylthio-arylacetic acid derivatives was prepared by condensation of thioamides with halo-acetals according to Hantzsch's method, and thioamides having the α-methylarylacetic acid moiety were conveniently obtained from haloaromatic nitro compounds by a combination of known methods. In the model reaction of O-phenyl thiocarbamate (XVIII) with chloro-diethylacetal, isolation of intermediates such as acyclic halo-compound (XIX) and 4-ethoxy-2-phenoxy-2-thiazoline (XX) clarified the reaction path for the formation of 2-phenoxythiazole (XXI). The analgesic and anti-inflammatory effects of the compounds studied were evaluated by using the acetic acid-induced writhing method in mice and the rat carrageenin paw edema method, respectively. 2- [4- (2-Thiazolyloxy) phenyl] propionic acid (XIVa) had the most favorable therapeutic ratio between activity and toxicity (in mice).

  根据Hantzsch方法，通过硫酰胺与卤代乙缩醛的缩合反应制备了一系列2-噻唑基氨基、2-噻唑基氧和2-噻唑基硫代芳基乙酸衍生物，而具有α-甲基芳基乙酸部分的硫酰胺则通过结合已知方法从卤代芳香硝基化合物中方便地获得。在O-苯基硫代氨基甲酸酯（XVIII）与氯代二乙缩醛的模型反应中，分离出无环卤代化合物（XIX）和4-乙氧基-2-苯氧基-2-噻唑啉（XX）等中间体，阐明了苯氧噻唑（XXI）的生成反应途径。通过小鼠的醋酸引起的扭体法和大鼠的角叉菜胶引起的足跖肿胀法，分别评估了所研究化合物的镇痛和抗炎作用。2-[4-（2-噻唑氧基）苯基]丙酸（XIVa）在活性与毒性之间具有最佳的治疗比（在小鼠中）。