4-乙酰氨基-3-氟苯甲酸 | 713-11-1

• 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: 4-乙酰氨基-3-氟苯甲酸
• 英文名称: 4-acetamido-3-fluorobenzoic acid
• 英文别名: 3-Fluor-4-acetamino-benzoesaeure；4-Acetylamino-3-fluorobenzoic acid
• CAS: 713-11-1
• 化学式: C₉H₈FNO₃
• mdl: MFCD00215837
• 分子量: 197.166
• InChiKey: HBZHYHPIAKNMBY-UHFFFAOYSA-N

物化性质

• 沸点：
  417.6±35.0 °C(Predicted)
• 密度：
  1.415±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-乙酰氨基-3-氟苯甲酸 在 盐酸 作用下， 以 乙醇 为溶剂， 生成 3-氟-4-氨基苯甲酸
  参考文献：
  名称：

  The Synthesis of the 3'-Fluoro and 3',5'-Difluoro Derivatives of 4-Amino-4-deoxy-N¹⁰-methylpteroylglutamic Acid (Methotrexate)¹

  摘要：

  DOI：

  10.1021/jo01067a079
• 作为产物：
  描述：

  3-氟甲苯 在 potassium permanganate 、 magnesium sulfate 作用下， 生成 4-乙酰氨基-3-氟苯甲酸
  参考文献：
  名称：

  The Synthesis of the 3'-Fluoro and 3',5'-Difluoro Derivatives of 4-Amino-4-deoxy-N¹⁰-methylpteroylglutamic Acid (Methotrexate)¹

  摘要：

  DOI：

  10.1021/jo01067a079

文献信息

• 5-aminoflavone derivatives
  申请人：Kyowa Hakko Kogyo Co., Ltd.

  公开号：US05539112A1

  公开（公告）日：1996-07-23

  5-Aminoflavone derivatives represented by the formula (I): ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are the same or different and represent hydrogen, substituted or unsubstituted lower alkyl, lower alkenyl, halogen-substituted or unsubstituted lower alkanoyl or lower alkoxycarbonyl, X.sup.1, X.sup.2, Y.sup.1 and Y.sup.2 are the same or different and represent hydrogen, halogen or lower alkyl, at least one of X.sup.1 and X.sup.2 represents halogen or lower alkyl, X.sup.3 represents hydrogen, substituted or unsubstituted lower alkyl, lower alkenyl, lower alkynyl, halogen, hydroxy, substituted or unsubstituted lower alkoxy, NR.sup.5 R.sup.6 (wherein R.sup.5 and R.sup.6 are the same or different and represent hydrogen, or substituted or unsubstituted lower alkyl, or R.sup.5 and R.sup.6 are taken together to form a heterocyclic group containing the nitrogen atom in the ring), lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, carboxy, lower alkoxycarbonyl, lower alkanoyl, adizo, cyano, substituted or unsubstituted carbamoyl or lower alkylthiothiocarbonyl: or pharmaceutically acceptable salts thereof.

  5-氨基黄酮衍生物的化学式（I）如下：其中R.sup.1、R.sup.2、R.sup.3和R.sup.4相同或不同，代表氢、取代或未取代的较低烷基、较低烯基、卤素取代或未取代的较低烷酰基或较低烷氧羰基，X.sup.1、X.sup.2、Y.sup.1和Y.sup.2相同或不同，代表氢、卤素或较低烷基，X.sup.1和X.sup.2中至少一个代表卤素或较低烷基，X.sup.3代表氢、取代或未取代的较低烷基、较低烯基、较低炔基、卤素、羟基、取代或未取代的较低烷氧基、NR.sup.5 R.sup.6（其中R.sup.5和R.sup.6相同或不同，代表氢，或取代或未取代的较低烷基，或R.sup.5和R.sup.6一起形成含有环中氮原子的杂环基），较低烷硫基、较低烷硫醇基、较低烷硫酰基、羧基、较低烷氧羰基、较低烷酰基、阿狄佐基、氰基、取代或未取代的氨基羰基或较低烷硫基硫羰基：或其药用盐。
• A Novel Pan-Negative-Gating Modulator of K_Ca2/3 Channels, Fluoro-Di-Benzoate, RA-2, Inhibits Endothelium-Derived Hyperpolarization–Type Relaxation in Coronary Artery and Produces Bradycardia In Vivo
  作者：Aida Oliván-Viguera、Marta Sofía Valero、Nicole Coleman、Brandon M. Brown、Celia Laría、María Divina Murillo、José A. Gálvez、María D. Díaz-de-Villegas、Heike Wulff、Ramón Badorrey、Ralf Köhler

  DOI：10.1124/mol.114.095745

  日期：2015.2

  Small/intermediate conductance KCa channels (KCa2/3) are Ca2+/calmodulin regulated K+ channels that produce membrane hyperpolarization and shape neurologic, epithelial, cardiovascular, and immunologic functions. Moreover, they emerged as therapeutic targets to treat cardiovascular disease, chronic inflammation, and some cancers. Here, we aimed to generate a new pharmacophore for negative-gating modulation of KCa2/3 channels. We synthesized a series of mono- and dibenzoates and identified three dibenzoates [1,3-phenylenebis(methylene) bis(3-fluoro-4-hydroxybenzoate) (RA-2), 1,2-phenylenebis(methylene) bis(3-fluoro-4-hydroxybenzoate), and 1,4-phenylenebis(methylene) bis(3-fluoro-4-hydroxybenzoate)] with inhibitory efficacy as determined by patch clamp. Among them, RA-2 was the most drug-like and inhibited human KCa3.1 with an IC50 of 17 nM and all three human KCa2 subtypes with similar potencies. RA-2 at 100 nM right-shifted the KCa3.1 concentration-response curve for Ca2+ activation. The positive-gating modulator naphtho[1,2- d ]thiazol-2-ylamine (SKA-31) reversed channel inhibition at nanomolar RA-2 concentrations. RA-2 had no considerable blocking effects on distantly related large-conductance KCa1.1, Kv1.2/1.3, Kv7.4, hERG, or inwardly rectifying K+ channels. In isometric myography on porcine coronary arteries, RA-2 inhibited bradykinin-induced endothelium-derived hyperpolarization (EDH)–type relaxation in U46619-precontracted rings. Blood pressure telemetry in mice showed that intraperitoneal application of RA-2 (≤100 mg/kg) did not increase blood pressure or cause gross behavioral deficits. However, RA-2 decreased heart rate by ≈145 beats per minute, which was not seen in KCa3.1−/− mice. In conclusion, we identified the KCa2/3–negative-gating modulator, RA-2, as a new pharmacophore with nanomolar potency. RA-2 may be of use to generate structurally new types of negative-gating modulators that could help to define the physiologic and pathomechanistic roles of KCa2/3 in the vasculature, central nervous system, and during inflammation in vivo.

  小/中等导电性KCa通道（KCa2/3）是由Ca2+/钙调蛋白调控的K+通道，能够引起膜超极化，从而影响神经、上皮、心血管和免疫功能。此外，它们被作为治疗心血管疾病、慢性炎症和某些癌症的治疗靶点。在此，我们的目标是为KCa2/3通道的负门控调节生成一个新的药效团。我们合成了一系列单和二苯酸酯，并确定了三种具有抑制效力的二苯酸酯[1,3-苯二亚甲基双(3-氟-4-羟基苯酸酯)（RA-2），1,2-苯二亚甲基双(3-氟-4-羟基苯酸酯)和1,4-苯二亚甲基双(3-氟-4-羟基苯酸酯)]，其抑制效能通过膜片钳测试确定。其中，RA-2是最具药物相似性的，IC50为17 nM，能够抑制人类KCa3.1，并以相似的效力抑制所有三种人类KCa2亚型。RA-2在100 nM时使KCa3.1的Ca2+激活浓度-反应曲线向右移动。正门控调节剂萘并[1,2-d]噻唑-2-氨基（SKA-31）在纳摩尔RA-2浓度下逆转了通道抑制。RA-2对远相关的大导电性KCa1.1、Kv1.2/1.3、Kv7.4、hERG或内向整流K+通道无显著阻断作用。在猪冠状动脉的等张肌肉测定中，RA-2抑制了由缓激肽引起的内皮源超极化（EDH）型松弛。在小鼠的血压遥测中，腹腔注射RA-2（≤100 mg/kg）未增加血压或造成明显的行为缺陷。然而，RA-2降低了心率约145次每分钟，而这在KCa3.1−/−小鼠中未见到。总之，我们鉴定了负门控调节剂KCa2/3，RA-2，作为一种具有纳摩尔效力的新药效团。RA-2可能有助于生成结构上新类型的负门控调节剂，这有助于阐明KCa2/3在血管、中央神经系统及炎症过程中的生理和病理机制作用。
• Development of second generation EP2 antagonists with high selectivity
  作者：Thota Ganesh、Jianxiong Jiang、Ray Dingledine

  DOI：10.1016/j.ejmech.2014.05.076

  日期：2014.7

  EP2 receptor has emerged as an important biological target for therapeutic intervention. In particular, it has been shown to exacerbate disease progression of a variety of CNS and peripheral diseases. Deletion of the EP2 receptor in mouse models recapitulates several features of the COX-2 inhibition, thus presenting a new avenue for anti-inflammatory therapy which could bypass some of the adverse side effects observed by the COX-2 inhibition therapy. We have recently reported a cinnamic amide class of EP2 antagonists with high potency, but these compounds exhibited a moderate selectivity against prostanoid receptor DP1. Moreover they possess acrylamide moiety in the structure, which may result in liver toxicity over longer period of use in a chronic disease model. Thus, we now developed a second generation compounds that devoid of the acrylamide functionality and possess high potency and improved (>1000-fold) selectivity to EP2 over other prostanoid receptors. (C) 2014 Elsevier Masson SAS. All rights reserved.
• 5-Aminoflavone derivatives, their preparation and their use as antibacterial, anti-estrogenic and/or antitumor agent
  申请人：KYOWA HAKKO KOGYO CO., LTD.

  公开号：EP0638566B1

  公开（公告）日：1999-01-07
• US5539112A
  申请人：——

  公开号：US5539112A

  公开（公告）日：1996-07-23