3-acetyl-5-fluoro-2-hydroxybenzoic acid | 67127-79-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-acetyl-5-fluoro-2-hydroxybenzoic acid
• 英文别名: 3'-carboxy-5'-fluoro-2'-hydroxy-acetophenone；2-hydroxy-3-acetyl-5-fluorobenzoic acid；3-acetyl-5-fluorosalicylic acid
• CAS: 67127-79-1
• 化学式: C₉H₇FO₄
• 分子量: 198.151
• InChiKey: HEYGVCYUKCBMEE-UHFFFAOYSA-N

物化性质

• 熔点：
  158-161 °C(Solv: ethanol (64-17-5); water (7732-18-5))
• 沸点：
  355.6±42.0 °C(Predicted)
• 密度：
  1.455±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 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：
  74.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-acetyl-5-fluoro-2-hydroxybenzoic acid 在 N-羟基-7-氮杂苯并三氮唑 、 双氧水 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 57.5h， 生成
  参考文献：
  名称：

  一种含氟的羧酸类黄酮-氨基酸衍生物的合成方法

  摘要：

  本发明公开了一种含氟的羧酸类黄酮‑氨基酸衍生物合成方法，属有机化学药物合成领域。该方法以5‑氟水杨酸为原料，首先合成含氟的羧酸类黄酮‑氨基酸衍生物所需的原料之一5‑氟‑3‑羟基黄酮‑8，2’‑二羧酸，然后将其和高水溶性改性氨基酸进行脱水缩合、水解等反应制备出含氟的羧酸类黄酮‑氨基酸衍生物，相比其他氨基酸衍生物的合成缩短了反应步骤，提高了产物收率，避免了催化加氢反应。合成制备的含氟羧酸类黄酮‑氨基酸衍生物收率较高，纯度高达99.7%以上。合成制备出的含氟羧酸类黄酮‑氨基酸衍生物水溶性好，生物活性强，对开发成新型、高效、低毒的活性药物将具有很好的应用价值。

  公开号：

  CN111875570A
• 作为产物：
  描述：

  5-氟水杨酸 在 三氯化铝 、 硫酸 作用下， 反应 4.0h， 生成 3-acetyl-5-fluoro-2-hydroxybenzoic acid
  参考文献：
  名称：

  羧基查耳酮的合成与构效关系：CysLT1（LTD4）受体拮抗剂的新系列。

  摘要：

  一系列新的2-，3-和4-（2-喹啉基甲氧基）-和3-和4- [2-（2-喹啉基）乙烯基]-取代的2'-，3的合成及CysLT1拮抗活性描述了'-，4'-或5'-羧基查耳酮。结构-活性关系研究表明，优选带负电的（酸性）部分，尽管在某些情况下腈或酯类似物也具有中等活性。喹啉部分可以在3-或4-位被取代。用其他芳香族基团取代该杂环会导致化合物具有可比的亲和力[2-（7-氯喹啉），1-（1-甲基-2-苯并咪唑）或1-（2-苯并噻唑）]或具有较低的活性[1 -（1-乙氧基乙基）-2-苯并咪唑，2-萘基或苯基]。喹啉和查耳酮部分可以通过乙烯基或甲氧基间隔基连接。对于3-和4-取代的查耳酮，查耳酮B环上的酸性部分可以连接至2'-，3'-，4'-或5'-位置。没有一般模式可以指定哪个取代位置产生最有效的化合物。该系列包含几种有效的CysLT1受体拮抗剂，其K（D）值接近纳摩尔范围，通过[3H] LTD4

  DOI：

  10.1021/jm960628d

文献信息

• Flavone derivative and medicine comprising the same
  申请人：KOWA CO. LTD.

  公开号：EP0834510A2

  公开（公告）日：1998-04-08

  This invention relates to a flavone derivative represented by the formula (1) or a salt thereof, and also to a medicine containing the same. wherein A represents H, halogen, phenyl, naphthyl, a group of the formula (2) in which X is H or halogen, B is -CH=CH-, -CH=N-, -N(R7)- (R7: lower alkyl or alkoxyalkyl), -O- or -S-; W represents a single bond, -CH2O- or -CH=CH-; at least one of R1 to R4 represents -COOH, -CN, alkyloxycarbonyl, tetrazolyl or -CONHR8 (R8: H, lower alkyl or phenylsulfonyl), the remainder thereof individually represent H, halogen, -OH, lower alkyl or lower alkoxyl; R5 represents H, -OH, lower alkoxyl, -O(CH2)mNR9R10 (R9,R10: H or lower alkyl, or coupled together with the adjacent N to form a phthalimido group; m: 1-5), or a group of the formula (3) (n: 1-5, ℓ: 2-3; and R6 represents H, halogen, lower alkyl or lower alkoxyl. A situation where A is H or halogen, W is a single bond and R5 is H is excluded. The compound (1) has excellent cys-LT1 receptor antagonism.

  本发明涉及一种由式（1）表示的黄酮衍生物或其盐，以及含有该衍生物的药物。 其中 A 代表 H、卤素、苯基、萘基、式（2）中 X 为 H 或卤素的基团，B 代表-CH＝CH-、-CH＝N-、-N(R7)-（R7：低级烷基或烷氧基烷基）、-O-或-S-；W 代表单键、-CH2O-或-CH＝CH-；R1 至 R4 中至少有一个代表-COOH、-CN、烷氧羰基、四唑基或-CONHR8（R8：代表 H、卤素、-OH、低级烷基或低级烷氧基；R5 代表 H、-OH、低级烷氧基、-O(CH2)mNR9R10（R9,R10：H或低级烷基，或与相邻的 N 偶联形成酞酰亚胺基团；m：1-5），或式（3）的基团（n：1-5，ℓ：2-3；R6 代表 H、卤素、低级烷基或低级烷氧基。不包括 A 为 H 或卤素、W 为单键、R5 为 H 的情况。化合物（1）具有优异的 cys-LT1 受体拮抗作用。
• CHALCONE DERIVATIVES AND DRUGS CONTAINING THE SAME
  申请人：KOWA CO. LTD.

  公开号：EP0902007A1

  公开（公告）日：1999-03-17

  This invention relates to chalcone derivatives represented by the following formula (1): wherein A represents a phenyl group, a quinolyl group or the like, W represents a vinylene group or the like, and R1 to R5 each independently represent a carboxyl, cyano, alkyloxycarbonyl or like group, or salts of the chalcone derivatives, and also to drugs containing them as effective ingredients. These compounds have excellent cys-LT receptor antagonism, and are useful as antiallergic agents or the like.

  本发明涉及下式（1）所代表的查尔酮衍生物： 其中 A 代表苯基、喹啉基或类似基团，W 代表乙烯基或类似基团，R1 至 R5 各自独立地代表羧基、氰基、烷氧基羰基或类似基团，或查尔酮衍生物的盐，还涉及含有它们作为有效成分的药物。 这些化合物具有优异的 cys-LT 受体拮抗作用，可用作抗过敏剂或类似药物。
• Synthesis, biological evaluation and 3D-QSAR studies of 3-keto salicylic acid chalcones and related amides as novel HIV-1 integrase inhibitors
  作者：Horrick Sharma、Shivaputra Patil、Tino W. Sanchez、Nouri Neamati、Raymond F. Schinazi、John K. Buolamwini

  DOI：10.1016/j.bmc.2011.01.047

  日期：2011.3

  HIV-1 integrase is one of the three most important enzymes required for viral replication and is therefore an attractive target for anti retroviral therapy. We herein report the design and synthesis of 3-keto salicylic acid chalcone derivatives as novel HIV-1 integrase inhibitors. The most active compound, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl)acryloyl] benzoic acid (25) was selectively active against integrase strand transfer, with an IC50 of 3.7 mu M. While most of the compounds exhibited strand transfer selectivity, a few were nonselective, such as 5-bromo-3-[3-(4-bromophenyl)acryloyl]-2-hydroxybenzoic acid (15), which was active against both 3'-processing and strand transfer with IC50 values of 11 +/- 4 and 5 +/- 2 mu M, respectively. The compounds also inhibited HIV replication with potencies comparable with their integrase inhibitory potencies. Thus, 5-bromo-2-hydroxy-3-[3-(2,3,6-trichlorophenyl) acryloyl] benzoic acid (25) and 5-bromo-3-[3-(4-bromophenyl) acryloyl]-2-hydroxybenzoic acid (15) inhibited HIV-1 replication with EC50 values of 7.3 and 8.7 mu M, respectively. A PHASE pharmacophore hypothesis was developed and validated by 3D-QSAR, which gave a predictive r(2) of 0.57 for an external test set of ten compounds. Phamacophore derived molecular alignments were used for CoMFA and CoMSIA 3D-QSAR modeling. CoMSIA afforded the best model with q(2) and r(2) values of 0.54 and 0.94, respectively. This model predicted all the ten compounds of the test set within 0.56 log units of the actual pIC(50) values; and can be used to guide the rational design of more potent novel 3-keto salicylic acid integrase inhibitors (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis and quantitative structure-activity relationships of antiallergic 2-hydroxy-N-(1H-tetrazol-5-yl)benzamides and N-(2-hydroxyphenyl)-1H-tetrazole-5-carboxamides
  作者：Roger E. Ford、Phillip Knowles、Edward Lunt、Stuart M. Marshall、Audrey J. Penrose、Christopher A. Ramsden、Anthony J. H. Summers、Joyce L. Walker、Derek E. Wright

  DOI：10.1021/jm00154a019

  日期：1986.4

  The synthesis and antiallergic activity of a series of 2-hydroxy-N-1H-tetrazol-5-ylbenzamides and isomeric N-(2-hydroxyphenyl)-1H-tetrazole-5-carboxamides is described. A relationship between structure and intravenous antiallergic activity in the rat passive cutaneous anaphylaxis (PCA) test has been established using a Hansch/Free-Wilson model and used to direct studies toward potent derivatives. The contribution of physicochemical properties to activity is discussed. One member of this series, N-(3-acetyl-5-fluoro-2-hydroxyphenyl)-1H-tetrazole-5-carboxamide (3f), which was selected for further evaluation, has an ID50 value of 0.16 mg/kg po and is 130 times more potent than disodium cromoglycate (DSCG) on intravenous administration.
• FORD, E.;KNOWLES, PH.;LUNT, E.;MARSHALL, S. M.;PENROSE, A. J.;RAMSDEN, A.+, J. MED. CHEM., 1986, 29, N 4, 538-549
  作者：FORD, E.、KNOWLES, PH.、LUNT, E.、MARSHALL, S. M.、PENROSE, A. J.、RAMSDEN, A.+

  DOI：——

  日期：——