ethyl 1-cyclopropyl-7-(2,6-dimethyl-4-pyridinyl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate | 123942-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 1-cyclopropyl-7-(2,6-dimethyl-4-pyridinyl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate
• 英文别名: ethyl 1-cyclopropyl-6,8-difluoro-7-(2,6-dimethyl-4-pyridinyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylate；ethyl 1-cyclopropyl-7-(2,6-dimethylpyridin-4-yl)-6,8-difluoro-4-oxoquinoline-3-carboxylate
• CAS: 123942-21-2
• 化学式: C₂₂H₂₀F₂N₂O₃
• 分子量: 398.409
• InChiKey: ABGMYRIJORAPFH-UHFFFAOYSA-N

物化性质

• 沸点：
  503.0±50.0 °C(Predicted)
• 密度：
  1.347±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  59.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 1-cyclopropyl-7-(2,6-dimethyl-4-pyridinyl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate 在 盐酸 作用下， 反应 2.0h， 以75%的产率得到1-环丙基-7-(2,6-二甲基吡啶-4-基)-6,8-二氟-4-氧代喹啉-3-羧酸
  参考文献：
  名称：

  一些新型的1-取代的1,4-二氢-4-氧代-7-吡啶基-3-喹啉羧酸的合成及抗菌活性。有效的抗葡萄球菌药物。

  摘要：

  3-和4-（三烷基锡烷基）吡啶与7-溴或7-氯1取代的1,4-二氢-4-氧代-3-喹啉羧酸酯的钯催化偶联提供了相应的1取代的1， 4-二氢-4-氧代-7-吡啶基-3-喹啉羧酸。研究了这些衍生物的抗菌活性，发现革兰氏阳性活性的最佳1位和7位取代基分别是环丙基和4-（2,6-二甲基吡啶基）。我们发现对于所研究的氟取代的衍生物，氟在喹诺酮核上的位置或氟原子的数目对于良好的革兰氏阳性活性似乎并不重要。对于1-环丙基7-（2,6-二甲基-4-吡啶基）衍生物，6-氟4a，8-氟10d，6,8-二氟10b和5,6,8-三氟8 所有这些都对金黄色葡萄球菌ATCC 29213具有相同的抗菌活性。7-（4-吡啶基）基团的取代与革兰氏阳性活性之间也存在相关性，特别是对金黄色葡萄球菌，这清楚地表明2,6-二甲基吡啶基组是最佳的。在这项研究中，针对金黄色葡萄球菌ATCC 29213的最有效药物的MIC50值为0.0

  DOI：

  10.1021/jm00014a005
• 作为产物：
  描述：

  4-溴-2,3,5,6-四氟苯甲酸 在 六甲基磷酰三胺 、 bis-triphenylphosphine-palladium(II) chloride 、 正丁基锂 、 五氯化磷 、 镍 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.75h， 生成 ethyl 1-cyclopropyl-7-(2,6-dimethyl-4-pyridinyl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate
  参考文献：
  名称：

  一些新型的1-取代的1,4-二氢-4-氧代-7-吡啶基-3-喹啉羧酸的合成及抗菌活性。有效的抗葡萄球菌药物。

  摘要：

  3-和4-（三烷基锡烷基）吡啶与7-溴或7-氯1取代的1,4-二氢-4-氧代-3-喹啉羧酸酯的钯催化偶联提供了相应的1取代的1， 4-二氢-4-氧代-7-吡啶基-3-喹啉羧酸。研究了这些衍生物的抗菌活性，发现革兰氏阳性活性的最佳1位和7位取代基分别是环丙基和4-（2,6-二甲基吡啶基）。我们发现对于所研究的氟取代的衍生物，氟在喹诺酮核上的位置或氟原子的数目对于良好的革兰氏阳性活性似乎并不重要。对于1-环丙基7-（2,6-二甲基-4-吡啶基）衍生物，6-氟4a，8-氟10d，6,8-二氟10b和5,6,8-三氟8 所有这些都对金黄色葡萄球菌ATCC 29213具有相同的抗菌活性。7-（4-吡啶基）基团的取代与革兰氏阳性活性之间也存在相关性，特别是对金黄色葡萄球菌，这清楚地表明2,6-二甲基吡啶基组是最佳的。在这项研究中，针对金黄色葡萄球菌ATCC 29213的最有效药物的MIC50值为0.0

  DOI：

  10.1021/jm00014a005

文献信息

• Pyrazoloquinolones as anticancer agents
  申请人：Sterling Winthrop Inc.

  公开号：US05334595A1

  公开（公告）日：1994-08-02

  Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, lower-alkyl, or trifluoromethyl; R.sub.2 is lower-alkyl, trifluoromethyl or CH.sub.2 Y where Y is hydroxy, chloro, lower-alkylamino or dilower-alkylamino R.sub.3 and R.sub.4 are each independently hydrogen or fluoro; R.sub.5 is hydrogen, lower-alkyl or (a) phenyl, 2-pyridyl, 4-pyridyl, 1-naphthyl or such groups substituted with one or more, the same or different, lower-alkyl, fluoro, hydroxy, or lower-alkoxy; (b) cycloalkyl or cycloalkyl substituted with amino, lower-alkylamino, dilower-alkylamino, formamido, acetamido, lower-alkyl, hydroxy, lower-alkoxy, trifluoromethyl, carboxy, lower-alkoxycarbonyl or halo, or cycloalkyl having a phenyl ring fused thereto; (c) A saturated heterocyclic 5- or 6-membered ring containing oxygen and/or nitrogen or such ring substituted with lower-alkyl; or (d) (CH.sub.2).sub.n -Z wherein n is an integer from about one to four and Z is amino, dilower-alkylamino, bis(hydroxylower-alkyl)lower-alkylamino; or a pharmaceutically acceptable acid addition salt thereof are topoiosmerase II inhibitors and are useful in the treatment of cancer in mammalian hosts.

  式子为##STR1##的化合物，其中R.sub.1为氢，低烷基或三氟甲基; R.sub.2为低烷基，三氟甲基或CH.sub.2 Y，其中Y为羟基，氯，低烷基氨基或二低烷基氨基; R.sub.3和R.sub.4各自独立地为氢或氟; R.sub.5为氢，低烷基或(a)苯基，2-吡啶基，4-吡啶基，1-萘基或带有一个或多个，相同或不同的低烷基，氟，羟基或低烷氧基置换的这些基团; (b)环烷基或环烷基被氨基，低烷基氨基，二低烷基氨基，甲酰胺基，乙酰胺基，低烷基，羟基，低烷氧基，三氟甲基，羧基，低烷氧羰基或卤素取代，或者环烷基上有一个苯环融合; (c)饱和的含氧和/或氮的5-或6-成员环或这样的环被低烷基取代; 或者(d)(CH.sub.2).sub.n -Z其中n是约为1到4的整数，Z是氨基，二低烷基氨基，双（羟基低烷基）低烷基氨基; 或其药学上可接受的酸加合物是拓扑异构酶II抑制剂，并且在哺乳动物宿主的癌症治疗中有用。
• Pyridinyl-quinolone compounds, their preparation and use
  申请人：Sterling Drug Inc.

  公开号：US05169853A1

  公开（公告）日：1992-12-08

  Fluorinated 1- cyclopropyl-7-(substituted-pyridinyl)-1,4-dihydro-4-oxo-3-quinolinecarboxy lic acids of the formula ##STR1## wherein R is hydrogen, R' and R" are hydrogen or fluoro, and Z is 3- or 4-pyridinyl substituted by alkyl groups or substituted alkyl groups, are superior antibacterial agents. They are prepared via a coupling reaction between the corresponding esters (R=alkyl) having a halo group in the 7-position and a substituted (trialkylstannyl)-pyridine.

  化合物的中文翻译如下：氟代1-环丙基-7-(取代吡啶基)-1,4-二氢-4-氧代-3-喹啉羧酸，其化学式为##STR1##其中R为氢，R'和R"为氢或氟，Z为被烷基或取代烷基取代的3-或4-吡啶基。它们是优良的抗菌剂。它们通过对应酯（R=烷基）在7位具有卤素基和取代（三烷基锡基）-吡啶之间的偶联反应制备而成。
• 4-Oxo-3-quinolinecarboxylic acids useful as antibacterial agents and preparation thereof
  申请人：STERLING WINTHROP INC.

  公开号：EP0309789A1

  公开（公告）日：1989-04-05

  A compound useful as an antibacterial agent having the formula: wherein: R is hydrogen or lower-alkyl; R′ is hydrogen, fluoro or -SR‴, where R‴ is phenyl, benzyl or lower-alkyl; R˝ is selected from hydrogen, fluoro and -SR‴, with the proviso that when R˝ is hydrogen, R′ is also hydrogen; or a pharmaceutically acceptable acid-addition salt thereof; or an alkali metal or amine salt of a compound where R is hydrogen as well as processes for the preparation thereof.

  一种可用作抗菌剂的化合物，其式如下 其中 R是氢或低级烷基； R′是氢、氟或-SR‴、 其中 R‴ 是苯基、苄基或低级烷基； R˝ 选自氢、氟和 -SR‴，但 R˝ 为氢时，R′ 也为氢； 或其药学上可接受的酸加成盐；或 R 为氢的化合物的碱金属盐或胺盐及其制备方法。
• Mammalian topoisomerase II inhibitory activity of 1-cyclopropyl-6,8-difluoro-1,4-dihydro-7-(2,6-dimethyl-4-pyridinyl)-4-oxo-3-quinolinecarboxylic acid and related derivatives
  作者：Mark P. Wentland、George Y. Lesher、Michael Reuman、Monte D. Gruett、Baldev Singh、Suzanne C. Aldous、Peter H. Dorff、James B. Rake、Susan A. Coughlin

  DOI：10.1021/jm00071a010

  日期：1993.9

  1-Cyclopropyl-6,8-difluoro-1,4-dihydro-7-(2,6-dimethyl-4-pyridinyl)-4-oxo-3-quinolinecarboxylic acid (1), a previously reported potent inhibitor of bacterial DNA gyrase, was found to be interactive with mammalian topoisomerase II (topo II). In a DNA-cleavage assay using topo II isolated from HeLa cells, 1 exhibited an EC50 value of 7.6 muM (VP-16; EC50 = 0.81 muM). A series of analogues modified at the 1-, 2-, 3-, 5-, and 7-positions of 1 were subsequently made and assessed for topo II inhibition. Compound 1 was considerably more potent than derivatives where the 1-substituent was alkyl, aryl, or H, or when N-c-C3H5 was replaced with S. The descarboxyl (i.e., 3-H) analogue had potency comparable to that of 1; when both these compounds were substituted at the 2-position with methyl or phenyl, an interesting relationship between activity and the conformation of the carboxyl group emerged. Upon replacement of the 5-H of 1 with NH2 or F, sustained potency was seen. No enhancement of activity was evident upon replacing the 7-substituent of 1 with other pyridinyl groups, 4-methyl-1-piperazinyl, or pyrrolidinyl groups; however, the 7-(4-hydroxyphenyl) analogue (CP-115,953) was 6-fold more potent than 1. The topo II inhibitory properties of 1 translated to modest in vitro cytotoxicity and in vivo activity versus P388.
• US5075319A
  申请人：——

  公开号：US5075319A

  公开（公告）日：1991-12-24