2-硝基-4-(三氟甲氧基)乙酰苯胺 | 787-57-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-硝基-4-(三氟甲氧基)乙酰苯胺
• 英文名称: 3-Nitro-4-acetylamino-phenyl-trifluormethyl-ether
• 英文别名: 2-nitro-4-(trifluoromethoxy)acetanilide；2-nitro-4-trifluoromethoxy-N-acetylaniline；4-trifluoromethoxy-2-nitroacetanilide；N-(2-nitro-4-trifluoromethoxy-phenyl)-acetamide；2-nitro-4-trifluoromethoxyacetylaniline；N-[2-nitro-4-(trifluoromethoxy)phenyl]acetamide
• CAS: 787-57-5
• 化学式: C₉H₇F₃N₂O₄
• 分子量: 264.161
• InChiKey: UCLBQTSVYJDQRU-UHFFFAOYSA-N

物化性质

• 熔点：
  94-96°C

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 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：
  84.2
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38

反应信息

• 作为反应物：
  描述：

  2-硝基-4-(三氟甲氧基)乙酰苯胺 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以95%的产率得到2-硝基-4-(三氟甲氧基)苯胺
  参考文献：
  名称：

  实用的，高收敛性，不对称合成的选择性PPARγ调节剂

  摘要：

  描述了一种实用的，高度收敛的，选择性PPARγ调节剂1的不对称合成。该抑制剂包含两个关键成分，即6-三氟甲氧基-3-酰基（6）和（R）-α-芳氧基丁酸衍生物（10）。开发了两种方法来克服在6-取代的吲哚的制备中遇到的区域选择性问题。第一个涉及碘代芳基烯胺的分子内Heck反应。第二个涉及2-硝基-4-三氟甲氧基苯胺和乙酸异丙烯酯之间的催化Meerwein芳基化反应的应用和随后的还原环化。通过相应的α-芳氧基-α，β-不饱和酸的不对称氢化制备α-芳氧基丁酸。四丁基碘化铵催化的两个片段偶联和酯水解完成了聚合合成。所描述的收敛合成用于制备> 3kg的药物物质1，其总收率为50％，且ee> 99.5％。

  DOI：

  10.1021/op8002882
• 作为产物：
  描述：

  对三氟甲氧基苯胺 在 硫酸 、 硝酸 作用下， 以 溶剂黄146 为溶剂， 反应 0.92h， 生成 2-硝基-4-(三氟甲氧基)乙酰苯胺
  参考文献：
  名称：

  Hypoxia-Selective Agents Derived from Quinoxaline 1,4-Di-N-oxides

  摘要：

  Hypoxic cells, which are a common feature of solid tumors, but not normal tissues, are resistant to both anticancer drugs and radiation therapy. Thus the identification of drugs with selective toxicity toward hypoxic cells is an important objective in anticancer chemotherapy. The benzotriazine di-N-oxide (SR 4233, Tirapazamine) has been shown to be an efficient and selective cytotoxin for hypoxic cells. Since the bioreductive activation of Tirapazamine is thought to be due to the presence of the 1,4-di-N-oxide moiety, a series of 3-aminoquinoxaline-2-carbonitrile 1,4-di-N-oxides with a range of electron-donating and -withdrawing substituents in the 6- and/or 7- positions has been synthesized and evaluated for toxicity to hypoxic cells. Electrochemical studies of the quinoxaline di-N-oxides and Tirapazamine showed that as the electron-withdrawing nature of the 6(7)-substituent increases, the reduction potential becomes more positive and the compound is more readily reduced. Apart from the unsubstituted 6a and the 6,7-dimethyl derivative 6c, the quinoxaline di-N-oxides have reduction potentials significantly more positive than Tirapazamine (E(pc)-0.90 V). The most potent cytotoxins to cells in culture were the 6,7,-dichloro and 6,7-difluoro derivatives 6i and 6l, which were 30-fold more potent than Tirapazamine. The 6(7)-fluoro and 6(7)-chloro compounds, 6e and 6h, showed the greatest hypoxia selectivity. Four of the compounds, 6e, 6f, 6h and 6i, killed the inner cells of multicellular tumor spheroids in vitro. In vivo Balb/c mice tolerated a dose of these four compounds twice the size of that of Tirapazamine. This study demonstrates that quinoxaline 1,4-di-N-oxides could provide useful hypoxia-selective therapeutic agents.

  DOI：

  10.1021/jm00010a023

文献信息

• [EN] COMBINATION OF MGLUR2 ANTAGONIST AND ACHE INHIBITOR FOR TREATMENT OF ACUTE AND/OR CHRONIC NEUROLOGICAL DISORDERS<br/>[FR] COMBINAISON D'ANTAGONISTE MGLUR2 ET D'INHIBITEUR ACHE DESTINEE AU TRAITEMENT DE TROUBLES NEUROLOGIQUES AIGUS ET/OU CHRONIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005014002A1

  公开（公告）日：2005-02-17

  The present invention relates to a method of treatment or prevention of acute and/or chronic neurological disorders, to a pharmaceutical composition comprising an inhibitor of acetylcholinesterase (AChE inhibitor) and a metabotropic Glutamate receptor 2 antagonist (mGluR2 antagonist), to the use of an AChE inhibitor and a mGluR2 antagonist in the preparation of a medicament, and. to kits comprising an AChE inhibitor and a mGluR2 antagonist.

  本发明涉及一种治疗或预防急性和/或慢性神经系统疾病的方法，涉及一种包含乙酰胆碱酯酶抑制剂（AChE抑制剂）和代谢型谷氨酸受体2拮抗剂（mGluR2拮抗剂）的药物组合物，涉及在制备药物中使用AChE抑制剂和mGluR2拮抗剂，以及包含AChE抑制剂和mGluR2拮抗剂的试剂盒。
• Novel Crystalline Forms of Antidiabetic Compounds
  申请人：Zhao Dalian

  公开号：US20080221198A1

  公开（公告）日：2008-09-11

  Novel crystalline forms of two indole compounds connected to phenoxyalkylcarboxylic acid groups are selective PPAR gamma partial agonists that are useful in the treatment of type 2 diabetes, hyperglycemia, obesity, dyslipidemia, and the metabolic syndrome. The novel crystal forms include a crystalline free acid dihydrate and crystalline free acid anhydrate of one compound and several crystalline forms of the free acid and the sodium salt of the second compound. The invention also relates to pharmaceutical compositions comprising these novel crystal forms, processes to prepare the crystal forms and their pharmaceutical compositions, and uses of the crystal forms in the treatment of type 2 diabetes and other PPAR gamma modulated diseases.

  两种吲哚化合物与苯氧烷基羧酸基团相连的新晶体形式是选择性PPARγ部分激动剂，可用于治疗2型糖尿病、高血糖、肥胖症、血脂异常和代谢综合征。新晶体形式包括一种化合物的结晶自由酸二水合物和结晶自由酸无水物，以及第二种化合物的自由酸和钠盐的几种晶体形式。本发明还涉及包含这些新晶体形式的制药组合物、制备晶体形式及其制药组合物的工艺，并将晶体形式用于治疗2型糖尿病和其他PPARγ调节疾病。
• Benzoureas Having Anti-Diabetic Activity
  申请人：Lui Weiguo

  公开号：US20080076810A1

  公开（公告）日：2008-03-27

  Benzourea compounds of Formula I having aryl-(CH 2 ) x -oxazolidinedione or aryl-(CH 2 ) x -thiazolidinedione substituents on one of the N atoms of the benzourea ring, wherein x is 0 or 1, are PPAR gamma agonists or partial agonists and are useful in the treatment and control of type II diabetes, including hyperglycemia and other symptoms such as dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and obesity, that are often associated with type 2 diabetes.

  具有在苯甲酰脲环的一个N原子上具有芳基-(CH2)x-噁唑啉二酮或芳基-(CH2)x-噻唑啉二酮取代基的公式I的苯甲酰脲化合物，其中x为0或1，是PPAR gamma激动剂或部分激动剂，并且在治疗和控制II型糖尿病，包括高血糖和其他症状，如血脂异常、高脂血症、高胆固醇血症、高三酰甘油血症和肥胖症方面非常有用，这些症状通常与2型糖尿病相关。
• Benzimidazolones: A New Class of Selective Peroxisome Proliferator-Activated Receptor γ (PPARγ) Modulators
  作者：Weiguo Liu、Fiona Lau、Kun Liu、Harold B. Wood、Gaochao Zhou、Yuli Chen、Ying Li、Taro E. Akiyama、Gino Castriota、Monica Einstein、Chualin Wang、Margaret E. McCann、Thomas W. Doebber、Margaret Wu、Ching H. Chang、Lesley McNamara、Brian McKeever、Ralph T. Mosley、Joel P. Berger、Peter T. Meinke

  DOI：10.1021/jm201061j

  日期：2011.12.22

  A series of benzimidazolone carboxylic acids and oxazolidinediones were designed and synthesized in search of selective PPAR gamma modulators (SPPAR gamma Ms) as potential therapeutic agents for the treatment of type II diabetes mellitus (T2DM) with improved safety profiles relative to rosiglitazone and pioglitazone, the currently marketed PPAR gamma full agonist drugs. Structure activity relationships of these potent and highly selective SPPAR gamma Ms were studied with a focus on their unique profiles as partial agonists or modulators. A variety of methods, such as X-ray aystallographic analysis, PPAR gamma transactivation coactivator profiling, gene expression profiling, and mutagenesis studies, were employed to reveal the differential interactions of these new analogues with PPAR gamma receptor in comparison to full agonists. In rodent models of T2DM, benzimidazolone analogues such as (5R)-5-(3-[3-(5-methoxybenzisoxazol-3-yl)benzimidazol-1-yl]methyl}phenyl)-5-methyloxazolidinedione (Si) demonstrated efficacy equivalent to that of rosiglitazone. Side effects, such as fluid retention and heart weight gain associated with PPAR gamma full agonists, were diminished with 51 in comparison to rosiglitazone based on studies in two independent animal models.
• WO2006/99077
  申请人：——

  公开号：——

  公开（公告）日：——