1-(2-氟-5-硝基苯基)-1H-吡咯 | 96623-75-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 1-(2-氟-5-硝基苯基)-1H-吡咯
• 英文名称: 4-fluoro-3-(1H-pyrrol-1-yl)nitrobenzene
• 英文别名: 1-(2-fluoro-5-nitrophenyl)-1H-pyrrole；4-nitro-2-pyrrolylfluorobenzene；1-(2-fluoro-5-nitrophenyl)pyrrole
• CAS: 96623-75-5
• 化学式: C₁₀H₇FN₂O₂
• mdl: MFCD02180646
• 分子量: 206.176
• InChiKey: QOIPFOMYLGXYDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-氟-5-硝基苯基)-1H-吡咯 在 Rh/Al₂O₃ sodium hydroxide 、 氢气 、 potassium carbonate 作用下， 以 二苯醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 90.0 ℃ 、405.3 kPa 条件下， 反应 5.5h， 生成 伊洛沙星
  参考文献：
  名称：

  Stefancich; Artico; Corelli, Farmaco, Edizione Scientifica, 1985, vol. 40, # 4, p. 237 - 248

  摘要：

  DOI：
• 作为产物：
  描述：

  2,5-二甲氧基四氢呋喃 、 2-氟-5-硝基苯胺 在 二氯甲烷 、 水 、 Brine 、 Sodium sulfate-III 、 hexanes 、 EtOAc hexanes 作用下， 以 溶剂黄146 为溶剂， 反应 8.0h， 以to afford the title compound as a light yellow solid (7.2 g, 78%)的产率得到1-(2-氟-5-硝基苯基)-1H-吡咯
  参考文献：
  名称：

  PROTEIN KINASE C INHIBITORS AND USES THEREOF

  摘要：

  本公开涉及一些化合物，这些化合物可用作蛋白激酶C（PKC）的抑制剂，因此可用于治疗通过PKC的活性介导或维持的各种疾病和障碍。本公开还涉及包含这些化合物的制药组合物，使用这些化合物治疗各种疾病和障碍的方法，制备这些化合物的过程以及在这些过程中有用的中间体。

  公开号：

  US20100184755A1

文献信息

• A stereoselective route to 6-substituted pyrrolo-1,5-benzoxazepinones and their analogues
  作者：Margherita Brindisi、Sandra Gemma、Gloria Alfano、Giridhar Kshirsagar、Ettore Novellino、Giuseppe Campiani、Stefania Butini

  DOI：10.1016/j.tetlet.2013.07.115

  日期：2013.9

  developed a novel and convenient stereoselective path for the preparation of pyrrolo-1,5-benzoxazepinones (PBOs). This innovative route envisaged the employment of (−)-menthol as convenient chiral auxiliary and a key SNAr for the stereoselective preparation of a tertiary aryl–alkyl ether. As a further advancement, we exploited this newly conceived synthetic route for the preparation of 2-substituted PBO analogues

  我们开发了一种新颖且方便的立体选择路径，用于制备吡咯并-1,5-苯并恶嗪酮（PBO）。这一创新途径设想了使用（-）-薄荷醇作为方便的手性助剂和关键的S N Ar，用于立体选择性地制备叔芳基-烷基醚。作为进一步的进步，我们利用这种新构想的合成路线来制备2取代的PBO类似物，以对其自身进行生物学评估或获得各种其他功能化选择。
• Protein Kinase C Inhibitors and Uses Thereof
  申请人：RIGEL PHARMACEUTICALS, INC.

  公开号：US20130143875A1

  公开（公告）日：2013-06-06

  This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本公开涉及一些化合物，这些化合物可用作蛋白激酶C（PKC）的抑制剂，并因此可用于治疗多种通过PKC的活性介导或维持的疾病和障碍。本公开还涉及包含这些化合物的制药组合物，使用这些化合物治疗各种疾病和障碍的方法，制备这些化合物的过程以及在这些过程中有用的中间体。
• Protein kinase C inhibitors and uses thereof
  申请人：Zhao Haoran

  公开号：US08394951B2

  公开（公告）日：2013-03-12

  This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本公开涉及一些化合物，这些化合物可作为蛋白激酶C（PKC）的抑制剂，因此可用于治疗通过PKC的活动介导或维持的各种疾病和障碍。本公开还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和障碍的方法，制备这些化合物的过程以及这些过程中有用的中间体。
• 1-Ethyl-6-fluoro-7-(1H-pirrol-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid: preparation and antimicrobial activities
  申请人：BIOCHEM DESIGN S.r.l.

  公开号：EP0155244A2

  公开（公告）日：1985-09-18

  The title compound 1-ethyl-6-fluoro-7-(1-pyrrol-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid is a quinolone carboxylic acid derivative of "oxacin" family bearing a fluorine atom and a pyrrol-1-yl moiety at 6 and 7 position respectively. It is represented by the following formula: and has been prepared by alkaline hydrolysis of the corresponding ethyl ester. The latter compound has been synthesized starting from 2-fluoro-5-nitroaniline. Treatment of this amine with diethoxytetrahydrofuran in glacial acetic acid afforded 4-fluoro-3-(1-H-pyrrol-1-yl)-nitrobenzene, which was then reduced by catalytic hydrogenation to 4-fluoro-3-(1 H-pyrrol-1-yl)aniline. Reaction of this compound with diethyl ethoxymethylene malonate and cyclization of the malonate obtained by heating in diphenyl ether at 120°C resulted in formation of ethyl ester of 6-fluoro-7-(1H-pyrrol-1-yl)quinoline-3-carboxylic acid. Ethylation of this ester with ethyl iodide in the presence of sodium carbonate gave the required 1-ethyl-6-fluoro-7-(1H-pyrrol-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl ester. The title acid exhibits high activity against Gram-positive bacteria, Enterobacteriaceae, Proteus and Pseudomonas, superior to those of nalidixic acid, piromidic acid and pipemidic acid; again, its antimicrobial spectrum is somewhat superior also to that of enoxacin. 1-Ethyl-6-fluoro-7-(1H-pyrrol-1-yl)-1,4-dihydro-4-oxo- quinoline-3-carboxylic acid is a new potent fluorinated quinolone antibacterial agent useful in the management of urinary tract and systemic infections. The present invention also relates to a process for the preparation of such compound.

  标题化合物 1-乙基-6-氟-7-(1-吡咯-1-基)-1,4-二氢-4-氧代喹啉-3-羧酸是一种 "氧杂喹啉 "家族的喹啉酮羧酸衍生物，其 6 位和 7 位分别含有一个氟原子和一个吡咯-1-基分子。其分子式如下 并通过碱水解相应的乙酯制备而成。后一种化合物是从 2-氟-5-硝基苯胺开始合成的。用冰醋酸中的二乙氧基四氢呋喃处理这种胺，可得到 4-氟-3-(1-H-吡咯-1-基)-硝基苯，然后通过催化氢化还原成 4-氟-3-(1-H-吡咯-1-基)苯胺。 将这种化合物与乙氧基亚甲基丙二酸二乙酯反应，并在 120°C 的二苯醚中加热使丙二酸二乙酯环化，生成 6-氟-7-(1H-吡咯-1-基)喹啉-3-羧酸乙酯。在碳酸钠存在下，用碘化乙酯对该酯进行乙酯化反应，得到了所需的 1-乙基-6-氟-7-(1H-吡咯-1-基)-1,4-二氢-4-氧代喹啉-3-羧酸乙酯。 标题酸对革兰氏阳性菌、肠杆菌科、变形杆菌和假单胞菌具有较高的活性，优于萘啶酸、吡咯咪啶酸和哌啶咪啶酸；其抗菌谱也略优于恩诺沙星。 1-乙基-6-氟-7-(1H-吡咯-1-基)-1,4-二氢-4-氧代-喹啉-3-羧酸是一种新型强效氟化喹诺酮类抗菌剂，可用于治疗尿路感染和全身感染。 本发明还涉及一种制备这种化合物的工艺。
• Site-directed Mutagenesis of Key Residues Unveiled a Novel Allosteric Site on Human Adenosine Kinase for Pyrrolobenzoxa(thia)zepinone Non-Nucleoside Inhibitors
  作者：Lida Savi、Margherita Brindisi、Gloria Alfano、Stefania Butini、Valeria La Pietra、Ettore Novellino、Luciana Marinelli、Andrea Lossani、Federico Focher、Caterina Cavella、Giuseppe Campiani、Sandra Gemma

  DOI：10.1111/cbdd.12630

  日期：2016.1

  Most nucleoside kinases, besides the catalytic domain, feature an allosteric domain which modulates their activity. Generally, non‐substrate analogs, interacting with allosteric sites, represent a major opportunity for developing more selective and safer therapeutics. We recently developed a series of non‐nucleoside non‐competitive inhibitors of human adenosine kinase (hAK), based on a pyrrolobenzoxa(thia)zepinone scaffold. Based on computational analysis, we hypothesized the existence of a novel allosteric site on hAK, topographically distinct from the catalytic site. In this study, we have adopted a multidisciplinary approach including molecular modeling, biochemical studies, and site‐directed mutagenesis to validate our hypothesis. Based on a three‐dimensional model of interaction between hAK and our molecules, we designed, cloned, and expressed specific, single and double point mutants of hAK (Q74A, Q78A, H107A, K341A, F338A, and Q74A‐F338A). Kinetic characterization of recombinant enzymes indicated that these mutations did not affect enzyme functioning; conversely, mutated enzymes are endowed of reduced susceptibility to our non‐nucleoside inhibitors, while maintaining comparable affinity for nucleoside inhibitors to the wild‐type enzyme. This study represents the first characterization and validation of a novel allosteric site in hAK and may pave the way to the development of novel selective and potent non‐nucleoside inhibitors of hAK endowed with therapeutic potential.