4-(乙酰基氨基)-3-羟基苯甲酸 | 10098-40-5

• 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: 4-(乙酰基氨基)-3-羟基苯甲酸
• 中文别名: 4-乙酰氨基-3-羟基苯甲酸
• 英文名称: 4-acetamido-3-hydroxybenzoic acid
• CAS: 10098-40-5
• 化学式: C₉H₉NO₄
• 分子量: 195.175
• InChiKey: WEMQDIKMQHBQIC-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  86.6
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  4-(乙酰基氨基)-3-羟基苯甲酸 在 盐酸 、 PPh₃-polystyrene 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Structural Requirements for Factor Xa Inhibition by 3-Oxybenzamides with Neutral P1 Substituents:  Combining X-ray Crystallography, 3D-QSAR, and Tailored Scoring Functions

  摘要：

  The design, synthesis, and structure-activity relationship of 3-oxybenzamides as potent inhibitors of the coagulation protease factor Xa are described on the basis of X-ray structures, privileged structure motifs, and SAR information. A total of six X-ray structures of fXa/inhibitor complexes led us to identify the major protein-ligand interactions. The binding mode is characterized by a lipophilic dichlorophenyl substituent interacting with Tyr228 in the protease S1 pocket, while polar parts are accommodated in S4. This alignment in combination with docking allowed derivation of 3D-QSAR models and tailored scoring functions to rationalize biological affinity and provide guidelines for optimization. The resulting models showed good correlation coefficients and predictions of external test sets. Furthermore, they correspond to binding site topologies in terms of steric, electrostatic, and hydrophobic complementarity. Two approaches to derive tailored scoring functions combining binding site and ligand information led to predictive models with acceptable predictions of the external set. Good correlations to experimental affinities were obtained for both AFMoC (adaptation of fields for molecular comparison) and the novel TScore function. The SAR information from 3D-QSAR and tailored scoring functions agrees with all experimental data and provides guidelines and reasonable activity estimations for novel fXa inhibitors.

  DOI：

  10.1021/jm049187l
• 作为产物：
  描述：

  4-乙酰基氨基-3-羟基-苯甲酸甲酯 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 24.0h， 以54%的产率得到4-(乙酰基氨基)-3-羟基苯甲酸
  参考文献：
  名称：

  鉴定邻羟基苯胺作为赖氨酸脱甲基酶5抑制剂的新型支架。

  摘要：

  Fe（II）/α-酮戊二酸依赖性赖氨酸脱甲基酶（KDMs）是多种疾病（包括癌症）的引人注目的药物靶标。在这项研究中，我们设计和筛选了有望用作Fe（II）螯合剂的邻位取代的酸酐，并确定了邻羟基苯胺作为KDM5A抑制剂的新型支架。用4-羧基-2-羟基甲酰苯胺（9c）的前药形式治疗人肺癌A549细胞时，组蛋白H3水平上的三甲基赖氨酸4含量增加，提示该细胞中存在KDM5抑制作用。

  DOI：

  10.1016/j.bmcl.2019.03.028

文献信息

• Metabolism of Benoxinate in Humans
  作者：Fumiyo Kasuya、Kazuo Igarashi、Miyoshi Fukui

  DOI：10.1002/jps.2600760408

  日期：1987.4

  The metabolism of benoxinate hydrochloride [2-(diethylamino)ethyl 4-amino-3-butoxybenzoate monohydrochloride; oxybuprocaine] was examined in humans after administration of a single oral dose. The drug was almost completely absorbed and was rapidly excreted in the urine (92.1% of dose in 9 h). Nine metabolites and unchanged drug were isolated from the urine and identified by comparison of TLC, GC, and

  苯甲酸酯盐酸盐[4-氨基-3-丁氧基苯甲酸2-（二乙氨基）乙基乙酯的盐酸盐；在单次口服给药后，在人体内检查了[oxybuprocaine]。该药物几乎被完全吸收，并迅速在尿液中排泄（在9小时内占剂量的92.1％）。从尿液中分离出九种代谢物和未改变的药物，并通过将TLC，GC和GC-MS与真实化合物进行比较进行鉴定。无法检测到任何反映出苯甲酸酯的丁基侧链最初丢失的代谢物。这表明酯部分比O-丁基侧链代谢更快。苯甲酸酯的水解产物3-丁氧基-4-氨基苯甲酸主要作为葡萄糖醛酸排泄（占剂量的70-90％），与微量的甘氨酸缀合物（占剂量的0.35％）一起排泄。此外，
• Structure-Based Inhibitors of Influenza Virus Sialidase. A Benzoic Acid Lead with Novel Interaction
  作者：Sangeeta Singh、Marek J. Jedrzejas、Gillian M. Air、Ming Luo、W. Graeme Laver、Wayne J. Brouillette

  DOI：10.1021/jm00017a005

  日期：1995.8

  for infection of the virus. The catalytic site is highly conserved among all known influenza variants, suggesting that this protein is a suitable target for drug intervention. The most potent known inhibitors are analogs of 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en), particularly the 4-guanidino derivative (4-guanidino-Neu5Ac2en). We utilized the benzene ring of 4-(N-acetylamino)benzoic

  流感病毒唾液酸酶是一种表面酶，对于感染病毒至关重要。在所有已知的流感变体中，催化位点均高度保守，表明该蛋白是药物干预的合适靶标。最有效的已知抑制剂是2-脱氧-2，3-二氢-N-乙酰神经氨酸（Neu5Ac2en），特别是4-胍基衍生物（4-胍基-Neu5Ac2en）的类似物。我们利用4-（N-乙酰氨基）苯甲酸的苯环作为环状模板替代Neu5Ac2en的二氢吡喃环。在这项研究中，准备了几种3-（N-酰基氨基）衍生物作为Neu5Ac2en甘油侧链的潜在替代物，并且发现其中一些与唾液酸酶的相同结合亚位相互作用。更重要的意义是观察到，迄今为止确定的最有效的流感唾液酸酶苯甲酸抑制剂（IC50 = 10 microM）3-胍基苯甲酸衍生物（相当于4-胍基-Neu5Ac2en的4-胍基）。与胍基结合子位点相反，唾液酸酶上的甘油结合子位点。因此，该苯甲酸衍生物提供了一种新化合物，该化合物以新颖的方式与流感唾液酸酶的催化​​位点相互作用。
• Design and Synthesis of a Highly Selective and <i>In Vivo</i>-Capable Inhibitor of the Second Bromodomain of the Bromodomain and Extra Terminal Domain Family of Proteins
  作者：Alex Preston、Stephen Atkinson、Paul Bamborough、Chun-wa Chung、Peter D. Craggs、Laurie Gordon、Paola Grandi、James R. J. Gray、Emma J. Jones、Matthew Lindon、Anne-Marie Michon、Darren J. Mitchell、Rab K. Prinjha、Francesco Rianjongdee、Inmaculada Rioja、Jonathan Seal、Simon Taylor、Ian Wall、Robert J. Watson、James Woolven、Emmanuel H Demont

  DOI：10.1021/acs.jmedchem.0c00605

  日期：2020.9.10

  better understand the contribution of each domain to their efficacy and improve their safety profile, selective inhibitors are required. This article discloses the profile of GSK046, also known as iBET-BD2, a highly selective inhibitor of the second bromodomains of the BET proteins that has undergone extensive pre-clinical in vitro and in vivo characterization.

  泛溴结构域和额外末端结构域（BET）抑制剂与BET蛋白质家族的八个溴结构域等价相互作用，并且在炎症或肿瘤学中的许多体外表型测定和体内临床前模型中显示出深远的功效。这些抑制剂中的许多已经发展到临床上，据报道药理学驱动的不良事件。为了更好地理解每个域对其功效的贡献并改善其安全性，需要选择性抑制剂。本文公开了GSK046（也称为iBET-BD2）的概况，它是BET蛋白第二个溴结构域的高度选择性抑制剂，已经在体外和体内进行了广泛的临床前研究 表征。
• Inhibitors of influenza virus neuraminidase and methods of making and
  申请人：The University of Alabama at Birmingham

  公开号：US05453533A1

  公开（公告）日：1995-09-26

  An influenza virus neuraminidase inhibitor, its analogs, its pharmaceutically acceptable salts, derivatives, and mixtures thereof having the following formula: ##STR1## where A is CO.sub.2 H, CO.sub.2 H.sub.3, NO.sub.2, SO.sub.3 H or PO.sub.3 H.sub.2, B is CH, N, O or S, R.sub.1 and R.sub.2 are H, NO.sub.2 or (CH.sub.m).sub.n X.sub.1 where m=1 or 2, n is an integer from 0 to 4 and X.sub.1 is guanidino, OH, NH.sub.2, SH, NO.sub.2, F, Cl, Br, I, CN, CF.sub.3, CO.sub.2 H, SO.sub.3 H or PO.sub.3 H.sub.2, R.sub.3 and R.sub.4 are H, (CH.sub.o).sub.p X.sub.2, (CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2, NH(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2, NHCO(CH.sub.o).sub.p CH.sub.2 X.sub.2 or NHCO(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2 where o=1 or 2, p is an integer from 0 to 4 and X.sub.2 is H, guanidino, OH, NH.sub.2, SH, NO.sub.2, CF.sub.3, CO.sub.2 H, SO.sub.3 H or PO.sub.3 H.sub.2 , R.sub.5 =H, OH, NH.sub.2, (CH.sub.k).sub.1 X.sub.3, CO(CH.sub.k).sub.1 X.sub.3, SO(CH.sub.k).sub.1 X.sub.3 or SO.sub.2 (CH.sub.k).sub.1 X.sub.3 where k=1 or 2, 1 is an integer from 0 to 4 and X.sub.3 is guanidino, OH, NH.sub.2, SH, NO.sub.2, CF.sub.3, CO.sub.2 H, SO.sub.3 H or PO.sub.3 H.sub.2, R.sub.6 is H, CH(OH)X.sub.4, CH(NH.sub.2)X.sub.4, COX.sub.4, SOX.sub.4, or SO.sub.2 X.sub.4, where X.sub.4 is H, CH.sub.3, CH.sub.3 CH.sub.2, CH.sub.3 CHCH.sub.3, CH.sub.3 CH.sub.2 CH.sub.2 or halogen substituted analogs of X.sub.4. The inhibitor in a composition with a pharmaceutically acceptable carrier. A method of inhibiting influenza virus neuraminidase where the inhibitor is administered to a subject in a pharmaceutically acceptable amount along with effective amounts of a pharmaceutically acceptable carrier. Methods of marking a pharmaceutical composition of an acceptable carrier and the inhibitor. Methods of treating and preventing a subject infected with influenza virus (type A or B) using the inhibitor.

  一种流感病毒神经氨酸酶抑制剂，其类似物，其药用可接受的盐，衍生物和混合物具有以下结构式：##STR1##其中A为CO.sub.2 H，CO.sub.2 H.sub.3，NO.sub.2，SO.sub.3 H或PO.sub.3 H.sub.2，B为CH，N，O或S，R.sub.1和R.sub.2为H，NO.sub.2或(CH.sub.m).sub.n X.sub.1，其中m=1或2，n是0到4的整数，X.sub.1为胍基，OH，NH.sub.2，SH，NO.sub.2，F，Cl，Br，I，CN，CF.sub.3，CO.sub.2 H，SO.sub.3 H或PO.sub.3 H.sub.2，R.sub.3和R.sub.4为H，(CH.sub.o).sub.p X.sub.2，(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2，NH(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2，NHCO(CH.sub.o).sub.p CH.sub.2 X.sub.2或NHCO(CH.sub.o).sub.p CHX.sub.2 CH.sub.2 X.sub.2，其中o=1或2，p是0到4的整数，X.sub.2为H，胍基，OH，NH.sub.2，SH，NO.sub.2，CF.sub.3，CO.sub.2 H，SO.sub.3 H或PO.sub.3 H.sub.2，R.sub.5=H，OH，NH.sub.2，(CH.sub.k).sub.1 X.sub.3，CO(CH.sub.k).sub.1 X.sub.3，SO(CH.sub.k).sub.1 X.sub.3或SO.sub.2(CH.sub.k).sub.1 X.sub.3，其中k=1或2，l是0到4的整数，X.sub.3为胍基，OH，NH.sub.2，SH，NO.sub.2，CF.sub.3，CO.sub.2 H，SO.sub.3 H或PO.sub.3 H.sub.2，R.sub.6为H，CH(OH)X.sub.4，CH(NH.sub.2)X.sub.4，COX.sub.4，SOX.sub.4或SO.sub.2 X.sub.4，其中X.sub.4为H，CH.sub.3，CH.sub.3 CH.sub.2，CH.sub.3 CHCH.sub.3，CH.sub.3 CH.sub.2 CH.sub.2或X.sub.4的卤素取代物。抑制剂与药用可接受的载体组成的组合物。一种抑制流感病毒神经氨酸酶的方法，其中将抑制剂与药用可接受的载体一起以药用可接受的剂量给予受试者。标记含有可接受载体和抑制剂的药物组合物的方法。使用该抑制剂治疗和预防感染流感病毒（A型或B型）的受试者的方法。
• Inhibitors of Histone Deacetylase
  申请人：Moradei Oscar

  公开号：US20080132503A1

  公开（公告）日：2008-06-05

  The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

  本发明涉及抑制组蛋白去乙酰化酶。本发明提供了抑制组蛋白去乙酰化酶酶活性的化合物和方法。本发明还提供了治疗细胞增殖性疾病和病症的组合物和方法。