4-fluoro-2-(phenylcarbonyl)benzoic acid | 33184-59-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-fluoro-2-(phenylcarbonyl)benzoic acid
• 英文别名: 2-Benzoyl-4-fluorobenzoic acid
• CAS: 33184-59-7
• 化学式: C₁₄H₉FO₃
• 分子量: 244.222
• InChiKey: MBXMUAIOMGRBTF-UHFFFAOYSA-N

物化性质

• 熔点：
  115-117 °C(Solv: isopropanol (67-63-0))
• 沸点：
  446.7±35.0 °C(Predicted)
• 密度：
  1.325±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-fluoro-2-(phenylcarbonyl)benzoic acid 在 盐酸 、 水 、 potassium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 4.5h， 生成 6-fluoro-1-oxo-4-phenyl-1H-isochromene-3-carboxylic acid
  参考文献：
  名称：

  Identification of 3-aminomethyl-1,2-dihydro-4-phenyl-1-isoquinolones: A new class of potent, selective, and orally active non-peptide dipeptidyl peptidase IV inhibitors that form a unique interaction with Lys554

  摘要：

  The design, synthesis, and structure-activity relationships of a new class of potent and orally active non-peptide dipeptidyl peptidase IV (DPP-4) inhibitors, 3-aminomethyl-1,2-dihydro-4-phenyl-1-isoquinolones, are described. We hypothesized that the 4-phenyl group of the isoquinolone occupies the S1 pocket of the enzyme, the 3-aminomethyl group forms an electrostatic interaction with the S2 pocket, and the introduction of a hydrogen bond donor onto the 6- or 7-substituent provides interaction with the hydrophilic region of the enzyme. Based on this hypothesis, intensive research focused on developing new non-peptide DPP-4 inhibitors has been carried out. Among the compounds designed in this study, we identified 2-[(3-aminomethyl-2-(2-methylpropyl)-1-oxo-4-phenyl-1,2-dihydro-6-isoquinolinyl) oxy] acetamide (35a) as a potent, selective, and orally bioavailable DPP-4 inhibitor, which exhibited in vivo efficacy in diabetic model rats. Finally, X-ray crystallography of 35a in a complex with the enzyme validated our hypothesized binding mode and identified Lys554 as a new target-binding site available for DPP-4 inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.059
• 作为产物：
  描述：

  (5-氟-2-甲基苯基)-苯基甲酮 在 chromium(VI) oxide 、 硫酸 作用下， 以 溶剂黄146 为溶剂， 生成 4-fluoro-2-(phenylcarbonyl)benzoic acid
  参考文献：
  名称：

  5-Aryl-2,3-dihydro-5H-imidazo[2,1-a]isoindol-5-ols. Novel class of anorectic agents

  摘要：

  A series of 5-aryl-2,3-dihydro-5H-imidazo[2,1-a]isoindol-5-ols (IV), prepared by the LiA1H4 reduction of the corresponding 9b-aryl-1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones (II), was evaluated for suppression of food consumption in rats. One member of this series, 5-p-chlorophenyl-2,3-dihydro-5H-imidazo[2,1-a]isoindol-5-ol (6, mazindol), was evaluated in squirrel and capuchin monkeys and found to have anorexic activity approximately equal to d-amphetamine.

  DOI：

  10.1021/jm00236a014

文献信息

• [EN] BENZOXAZOCINES AND THEIR THERAPEUTIC USE AS MONOAMINE REUPTAKE INHIBITORS<br/>[FR] BENZOXAZOCINES ET UTILISATION THERAPEUTIQUE DE CELLES-CI COMME INHIBITEURS DU RECAPTAGE DE LA MONOAMINE
  申请人：ARAKIS LTD

  公开号：WO2005103019A1

  公开（公告）日：2005-11-03

  Compounds having therapeutic utility are of general formula (1) wherein R, is H, C 1-C6 alkyl optionally substituted with F or C3-C6 cycloalkyl or C2-C4 alkenyl; A is O, CH2 or S(O)n where n is 0-2; one of W, X, Y and Z is N, CH or CR3 and the others are CH; R2 is C5-C6 heteroaryl, C5-C10 cycloalkyl or cycloalkenyl optionally containing one or more heteroatoms selected from O, N and S(O)n where n is 0-2, and optionally substituted with R3; or a phenyl group optionally substituted in one or more positions with one or more substituents independently selected from halogen, CN, CF3, C1-C6 alkyl and OR1, or the phenyl group is fused to a five or six membered ring which may be carbocyclic, heterocyclic (containing 1-2 heteroatoms selected from O, N and S), aromatic or heteroaromatic (containing 1-2 heteroatoms selected from O and N); R3 is selected from halogen; CF3; CN; OR5; SO2N(R5)2; COR5; CO2R5; CON(R5)2; NR1,COR4; NR1SO2R4; NR1CO2R4; NR1,CON(R5)2; OC1-C6 alkyl substituted with R3; C1-C6 alkyl optionally substituted with unsubstituted R3; C3-C6 cycloalkyl optionally substituted with unsubstituted R3; C2-Cs alkenyl optionally substituted with unsubstituted R3; C2-Cs alkynyl optionally substituted with unsubstituted R3; aryl optionally substituted with unsubstituted R3; and five or six membered aromatic heterocycles containing 1-4 heteroatoms selected from N and O; R4 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, aryl and heteroaryl; and R5 is H, C1-C6 alkyl; C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, aryl or heteroaryl and is the same as or different to another R5; or a pharmaceutically acceptable salt thereof.

  具有治疗效用的化合物具有一般式（1），其中R是H，C1-C6烷基，可选择地取代为F或C3-C6环烷基或C2-C4烯基；A是O，CH2或S（O）n，其中n为0-2；W、X、Y和Z中的一个是N、CH或CR3，其他的是CH；R2是C5-C6杂环芳基，C5-C10环烷基或环烯基，可选择地含有一个或多个选自O、N和S（O）n（n为0-2）的杂原子，并可选择地取代为R3；或者是苯基，可选择地在一个或多个位置上取代为一个或多个从卤素、CN、CF3、C1-C6烷基和OR1中独立选择的取代基，或者苯基与一个五元或六元环融合，该环可以是碳环、杂环（含有1-2个选自O、N和S的杂原子）、芳香环或杂芳环（含有1-2个选自O和N的杂原子）；R3选自卤素、CF3、CN、OR5、SO2N（R5）2、COR5、CO2R5、CON（R5）2、NR1、COR4、NR1SO2R4、NR1CO2R4、NR1、CON（R5）2、OC1-C6烷基取代为R3、C1-C6烷基可选择地取代为未取代的R3、C3-C6环烷基可选择地取代为未取代的R3、C2-Cs烯基可选择地取代为未取代的R3、C2-Cs炔基可选择地取代为未取代的R3、芳基可选择地取代为未取代的R3、和含有1-4个选自N和O的杂原子的五元或六元芳香杂环；R4是C1-C6烷基、C2-C6烯基、C2-C6炔基、C3-C6环烷基、芳基和杂芳基；R5是H、C1-C6烷基、C2-C6烯基、C2-C6炔基、C3-C6环烷基、芳基或杂芳基，并且与另一个R5相同或不同；或其药学上可接受的盐。
• Metal-Free Arylation-Lactonization Sequence of <i>γ</i> -Alkenoic Acids Using Anilines as Aryl Radical Precursors
  作者：Diego Felipe-Blanco、Jose C. Gonzalez-Gomez

  DOI：10.1002/ejoc.201901679

  日期：2019.12.19

  This work was generously supported by the Spanish Ministerio de Economia y Competitividad (MINECO; grant no. CTQ2017–88171-P) and the Generalitat Valenciana (GV; grant no. AICO/2017/007).

  这项工作得到了西班牙经济和竞争部长 (MINECO; 授予号 CTQ2017–88171-P) 和 Generalitat Valenciana (GV; 授予号 AICO/2017/007) 的慷慨支持。
• Novel benzoxazocines and their therapeutic use
  申请人：Baxter Douglas Andrew

  公开号：US20060019940A1

  公开（公告）日：2006-01-26

  Compounds of the general formula (1), wherein one of W, X, Y and Z is N or CR 4 and the others are each CH; and R 4 is a specified substituent. These compounds inhibit monocamine reuptake, and are useful in the treatment of pain, emesis depression, post traumatic stress disorders, attention deficit disorders, obsessive compulsive disorders, pre-menstrual syndrome, substance abuse and sexual dysfunction.

  通式（1）的化合物中，其中W、X、Y和Z中的一个是N或CR4，其他的都是CH；而R4是一个指定的取代基。这些化合物抑制单胺再摄取，可用于治疗疼痛、呕吐、抑郁、创伤后应激障碍、注意力缺陷障碍、强迫症、经前综合症、物质滥用和性功能障碍。
• Aryl-fused and hetaryl-fused-2, 4-diazepine and 2, 4-diazocine antiarrhythmic agents
  申请人：STERLING DRUG INC.

  公开号：EP0475527A2

  公开（公告）日：1992-03-18

  Aryl-fused- and hetaryl-fused-2,4-diazepines of formula XXXVI, benzodiazocines of formula XXX, benzodiazepines of formula II δ-aminoamides of formula III and aryldimethanamines of formula XXXVII wherein Ais an aryl, alicyclic or or hetaryl ring; R¹is hydrogen, alkyl, aryl or hetaryl; R²is hydrogen, alkyl, substituted alkyl, or aryl; R³is hydrogen, alkyl, aryl, aralkyl, hetaryl or heteroatom substituted alkyl or aralkyl; R⁴is hydrogen, alkyl or substituted alkyl; R⁵is hydrogen, alkyl, aryl or hetaryl; R⁶is hydrogen, alkyl, alkoxy, nitro, alkylsulfonamido, halogen or a fused benzene ring; R⁹is hydrogen, alkyl, substituted alkyl or aralkyl; and R¹⁰is hydrogen, alkyl, substituted alkyl, aryl or hetaryl. This invention further relates to processes for the preparation of, pharmaceutical compositions containing, and methods of treating cardiac arrhythmia with the compounds of formulae XXXVI, XXX, II, III, and XXXVII.

  式 XXXVI 的芳基融合-和正十八烷基融合-2,4-二氮杂卓、式 XXX 的苯并二氮杂卓、式 II 的苯并二氮杂卓 式 III 的δ-氨基酰胺和式 XXXVII 的芳基二甲胺 其中 A 是芳基环、脂环或正庚基环； R¹是氢、烷基、芳基或正十八烷基； R² 是氢、烷基、取代烷基或芳基； R³ 是氢、烷基、芳基、芳烷基、正烷基或杂原子取代的烷基或芳烷基； R⁴ 是氢、烷基或取代的烷基； R⁵ 是氢、烷基、芳基或正十八烷基； R⁶ 是氢、烷基、烷氧基、硝基、烷基磺酰胺基、卤素或融合苯环； R𠞙 是氢、烷基、取代烷基或芳烷基；以及 R¹⁰是氢、烷基、取代烷基、芳基或正烷基。 正十八烷基。 本发明进一步涉及用式 XXXVI、XXX、II、III 和 XXXVII 的化合物制备心律失常的工艺、含有这些化合物的药物组合物以及治疗心律失常的方法。
• Aryl-fused and hetaryl-fused-2,4-diazocine antiarrhythmic agents
  申请人：STERLING WINTHROP INC.

  公开号：EP0597540A1

  公开（公告）日：1994-05-18

  Aryl-fused- and hetaryl-fused-2,4-diazepines of formula XXXVI, wherein    A is an aryl, cycloalkyl or hetaryl or substituted aryl ring    R¹ is hydrogen, alkyl, aralkyl, aryl, hetaryl or substituted aryl;    R² is hydrogen, alkyl, aralkyl, aryl or substituted alkyl or aryl;    R³ is alkyl, aryl, aralkyl, hetaryl or heteroatom substituted alkyl, aryl, aralkyl or hetaryl;    R⁴ is hydrogen, alkyl or substituted alkyl;    R⁵ is hydrogen, alkyl, aryl, aralkyl, hetaryl or substituted aryl, pharmaceutical compositions containing these and methods of treating cardiac arrhythmia with the compounds of formula XXXVI are disclosed.

  式 XXXVI 的芳基融合-2,4-二氮杂卓和正十八烷基融合-2,4-二氮杂卓、 其中 A 是芳基环、环烷基环、正十八烷基环或取代的芳基环 R¹ 是氢、烷基、芳烷基、芳基、正烷基或取代的芳基； R² 是氢、烷基、芳烷基、芳基或取代的烷基或芳基； R³ 是烷基、芳基、芳烷基、正烷基或杂原子取代的烷基、芳基、芳烷基或正烷基； R⁴ 是氢、烷基或取代的烷基； R⁵ 是氢、烷基、芳基、芳烷基、庚基或取代的芳基、 本发明公开了含有这些化合物的药物组合物以及用式 XXXVI 化合物治疗心律失常的方法。