2-(1-Chloroethyl)-4-hydroxy-N-(2-thiazolyl)-8-(trifluoromethyl)-3-quinolinecarboxamide | 80777-24-8

• 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: 2-(1-Chloroethyl)-4-hydroxy-N-(2-thiazolyl)-8-(trifluoromethyl)-3-quinolinecarboxamide
• 英文别名: 2-(1-chloroethyl)-4-hydroxy-N-(2-thiazolyl)-8-trifluoromethyl-3-quinoline-carboxamide；2-(1-chloroethyl)-4-oxo-N-(1,3-thiazol-2-yl)-8-(trifluoromethyl)-1H-quinoline-3-carboxamide
• CAS: 80777-24-8
• 化学式: C₁₆H₁₁ClF₃N₃O₂S
• 分子量: 401.796
• InChiKey: FEWLKRBEOUIQGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  99.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(1-Chloroethyl)-4-hydroxy-N-(2-thiazolyl)-8-(trifluoromethyl)-3-quinolinecarboxamide 在 溶剂黄146 、 乙醚 、 乙酸盐 作用下， 以 溶剂黄146 为溶剂， 反应 1.15h， 以to obtain 5.4 g of 1,3-dihydro-3-methyl-1-[(2-thiazolyl)-imino]-5-trifluoromethyl-furo[3,4-b]quinoline-9-ol in the form of an acetate的产率得到3-Methyl-1-[(Z)-thiazol-2-ylimino]-5-trifluoromethyl-1,3-dihydro-furo[3,4-b]quinolin-9-ol
  参考文献：
  名称：

  Preparation of amides of 4-hydroxy-3-quinoline-carboxylic acid

  摘要：

  化合物的名称为4-羟基-3-喹啉甲酰胺，化学式如下：##STR1## 其中X位于5、6、7或8位，选自氢、卤素、1至5个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--OCF.sub.3和--SCF.sub.3的群组，R.sub.1选自氢和1至4个碳原子的烷基，R.sub.2选自噻唑基、4,5-二氢噻唑基、吡啶基、噁唑基、异噁唑基、咪唑基、嘧啶基和四唑基，均可选用1至4个碳原子的烷基和苯基，后者可选择至少一种取代基，所述取代基选自--OH、1至4个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--NO.sub.2和卤素的群组，R.sub.3选自氢、1至4个碳原子的烷基和芳基，R.sub.4选自氢、1至4个碳原子的烷基和芳基，R.sub.5选自氢、1至4个碳原子的烷基和##STR2##，R.sub.5'选自1至4个碳原子的烷基和芳基。该化合物及其中间体具有很好的镇痛活性和非常重要的抗炎活性，以及其非毒性、药学上可接受的酸盐和非毒性、药学上可接受的碱盐。

  公开号：

  US04596875A1
• 作为产物：
  描述：

  2-氨基-3-(三氟甲基)苯甲酸 在 4-二甲氨基吡啶 、 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 生成 2-(1-Chloroethyl)-4-hydroxy-N-(2-thiazolyl)-8-(trifluoromethyl)-3-quinolinecarboxamide
  参考文献：
  名称：

  Clemence, Francois; Martret, Odile Le; Collard, Jeannine, Journal of Heterocyclic Chemistry, 1984, vol. 21, p. 1345 - 1353

  摘要：

  DOI：

文献信息

• 4-Hydroxy-3-quinolinecarboxamides with antiarthritic and analgesic activities
  作者：Francois Clemence、Odile Le Martret、Francoise Delevallee、Josette Benzoni、Alain Jouanen、Simone Jouquey、Michel Mouren、Roger Deraedt

  DOI：10.1021/jm00402a034

  日期：1988.7

  by the oral route as antiinflammatory agents in carrageenin-induced foot edema and adjuvant-induced arthritis and as analgesic agents in the acetic acid induced writhing test. Among the most active molecules, some have shown both analgesic and acute antiinflammatory activities. Others, such as compounds 24, 37, and 52, were only powerful peripherally acting analgesics. Compound 52, being active at 1

  已经合成了一系列的4-羟基-3-喹啉甲酰胺，并通过口服途径评价了角叉菜胶引起的足部水肿和佐剂引起的关节炎中的抗炎药，以及乙酸引起的扭体试验中的镇痛药。在最活跃的分子中，有些已经显示出止痛和急性抗炎活性。其他化合物，例如化合物24、37和52，仅是有效的外周镇痛药。活性为1 mg / kg（ED50）的化合物52是该系列中最有效的化合物。一些在2位上被醇，酯或胺官能团取代的类似物显示出与吡罗昔康相同的有效抗关节炎活性，并且在炎症和伤害感受的急性试验中也具有活性。他们抑制了微摩尔浓度的环氧合酶和5-脂氧合酶的活性。化合物102（RU 43526）显示出有效的抗关节炎活性（佐剂诱发的关节炎，ED50 = 0.7 mg / kg，口服）和胃肠道耐受性（ED100大于250 mg / kg，口服），因此，目前正在接受广泛的药理评估。
• 4-Hydroxy-3-quinoline-carboxylic acid derivatives
  申请人：Roussel Uclaf

  公开号：US04486438A1

  公开（公告）日：1984-12-04

  Novel 4-hydroxy-3-quinoline-carboxamides of the formula ##STR1## wherein X is in the 5,6,7 or 8-position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --OCF.sub.3 and --SCF.sub.3, R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 is selected from the group consisting of thiazolyl, 4,5-dihydro-thiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidinyl and tetrazolyl, all optionally substituted with alkyl of 1 to 4 carbon atoms and phenyl optionally substituted with at least one member of the group consisting of --OH, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --NO.sub.2 and halogen R.sub.3 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.4 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.5 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and ##STR2## R.sub.5 ' is selected from the group consisting of alkyl of 1 to 4 carbon atoms and aryl and their non-toxic, pharmaceutically acceptable acid addition salts and salts with non-toxic, pharmaceutically acceptable bases having very good analgesic activity and a non-negligible anti-inflammatory activity and novel intermediates.

  新型4-羟基-3-喹啉羧酰胺的化学式为##STR1##其中X位于5,6,7或8位，并选自由氢、卤素、1至5个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--OCF.sub.3和--SCF.sub.3组成的群，R.sub.1选自由氢和1至4个碳原子的烷基组成的群，R.sub.2选自噻唑基、4,5-二氢噻唑基、吡啶基、噁唑基、异噁唑基、咪唑基、嘧啶基和四唑基组成的群，所有这些基可选择地用1至4个碳原子的烷基和苯基替代，所述苯基可选择地用--OH、1至4个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--NO.sub.2和卤素中的至少一种成员替代，R.sub.3选自由氢、1至4个碳原子的烷基和芳基组成的群，R.sub.4选自由氢、1至4个碳原子的烷基和芳基组成的群，R.sub.5选自由氢、1至4个碳原子的烷基和##STR2##R.sub.5'选自由1至4个碳原子的烷基和芳基组成的群，以及它们的无毒、药学上可接受的酸盐和与无毒、药学上可接受的碱盐具有非常好的镇痛活性和不可忽视的抗炎活性的盐和新型中间体。
• Analgesic 4-hydroxy-3-quinolinecarboxamides
  申请人：Roussel Uclaf

  公开号：US04397856A1

  公开（公告）日：1983-08-09

  Novel compounds of the formula ##STR1## wherein X is in the 5,6,7 or 8 position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, CF.sub.3 O--, CF.sub.3 S-- and CF.sub.3 --, R.sub.1 ' is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 ' is selected from the group consisting of hydrogen or an optionally unsaturated ring able to contain one or more heteroatoms of the group consisting of --S--, --O-- and --N-- optionally substituted with one or more members of the group consisting of (a) halogens, (b) alkyl of 1 to 4 carbon atoms optionally substituted with NH.sub.2, --NHAlK or --N---(AlK).sub.2 and AlK is alkyl of 1 to 3 carbon atoms, (c) phenyl, (d) alkoxy of 1 to 4 carbon atoms, (e) --OH, (f) --CF.sub.3 and (g) --NO.sub.2 or R.sub.1 ' together with the nitrogen atom to which they are attached form an optionally unsaturated ring, the said ring then being connected to the nitrogen atom by a double bond, R.sub.3 is selected from the group consisting of hydrogen, halogen and alkyl of 1 to 4 carbon atoms, R.sub.4 is selected from the group consisting of hydrogen and halogen, R.sub.5 is a halogen with the proviso that R.sub.3, R.sub.4 and R.sub.5 can not all be fluorine and R.sub.6 is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms and an acyl of an organic carboxylic acid of 2 to 8 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts and their salts with non-toxic, pharmaceutically acceptable bases having a remarkable analgesic activity, a very weak anti-inflammatory activity and a good tolerance by the gastrointestinal system and their preparation and their intermediates.

  该化合物的新型化合物的公式为##STR1##其中X位于5、6、7或8位置，选自氢、卤素、1至5个碳原子的烷基、1至4个碳原子的烷氧基、CF.sub.3 O--、CF.sub.3 S--和CF.sub.3--的群组，R.sub.1'选自氢和1至4个碳原子的烷基，R.sub.2'选自氢或可含有--S--、--O--和--N--等一种或多种杂原子的可选不饱和环，可用含有(a)卤素、(b)1至4个碳原子的烷基（可选用NH.sub.2、--NHAlK或--N---(AlK).sub.2替代）、AlK为1至3个碳原子的烷基、(c)苯基、(d)1至4个碳原子的烷氧基、(e)--OH、(f)--CF.sub.3和(g)--NO.sub.2的一种或多种成员替代的一种或多种成员，或R.sub.1'与它们连接的氮原子一起形成可选不饱和环，则该环通过双键连接到氮原子，R.sub.3选自氢、卤素和1至4个碳原子的烷基，R.sub.4选自氢和卤素，R.sub.5是卤素，但R.sub.3、R.sub.4和R.sub.5不能都是氟，R.sub.6选自氢、1至8个碳原子的烷基和2至8个碳原子的有机羧酸酰基，以及其无毒、药用可接受的酸盐和其与非毒、药用可接受的碱的盐，具有显著的镇痛活性、极弱的抗炎活性和对胃肠系统的良好耐受性，以及它们的制备和中间体。
• Benzoxazine-4-one intermediates
  申请人：Roussel Uclaf

  公开号：US04518775A1

  公开（公告）日：1985-05-21

  Novel compounds of the formula ##STR1## wherein X is in the 5,6,7 or 8 position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, CF.sub.3 O--, CF.sub.3 S-- and CF.sub.3 -, R.sub.1 ' is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 ' is selected from the group consisting of hydrogen or an optionally unsaturated ring able to contain one or more heteroatoms of the group consisting of --S--, --O-- and --N-- optionally substituted with one or more members of the group consisting of (a) halogens, (b) alkyl of 1 to 4 carbon atoms optionally substituted with NH.sub.2, --NHAlK or --N--(AlK).sub.2 and AlK is alkyl of 1 to 3 carbon atoms, (c) phenyl, (d) alkoxy of 1 to 4 carbon atoms, (e) --OH, (f) --CF.sub.3 and (g) --NO.sub.2 or R.sub.1 ' and R.sub.2 ' together with the nitrogen atom to which they are attached form an optionally unsaturated ring, the said ring then being connected to the nitrogen atom by a double bond, R.sub.3 is selected from the group consisting of hydrogen, halogen and alkyl of 1 to 4 carbon atoms, R.sub.4 is selected from the group consisting of hydrogen and halogen, R.sub.5 is a halogen with the proviso that R.sub.3, R.sub.4 and R.sub.5 can not all be fluorine and R.sub.6 is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms and an acyl of an organic carboxylic acid of 2 to 8 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts and their salts with non-toxic, pharmaceutically acceptable bases having a remarkable analgesic activity, a very weak anti-inflammatory activity and a good tolerance by the gastrointestinal system and their preparation and their intermediates.

  化合物的新型式为##STR1##其中X位于5、6、7或8位，并选择自氢、卤素、1至5个碳原子的烷基、1至4个碳原子的烷氧基、CF.sub.3 O--、CF.sub.3 S--和CF.sub.3-的群组中，R.sub.1 '选择自氢和1至4个碳原子的烷基，R.sub.2 '选择自氢或可选含有一个或多个杂原子的不饱和环，所述杂原子的群组包括--S--、--O--和--N--，可选地用群组中的一个或多个成员取代，所述成员的群组包括(a)卤素、(b)1至4个碳原子的烷基，可选地用NH.sub.2、--NHAlK或--N--(AlK).sub.2取代，其中AlK为1至3个碳原子的烷基，(c)苯基、(d)1至4个碳原子的烷氧基、(e) --OH、(f) --CF.sub.3和(g) --NO.sub.2或R.sub.1 '和R.sub.2 '与它们所连接的氮原子一起形成可选的不饱和环，所述环然后通过双键连接到氮原子，R.sub.3选择自氢、卤素和1至4个碳原子的烷基，R.sub.4选择自氢和卤素，R.sub.5为卤素，但R.sub.3、R.sub.4和R.sub.5不能全为氟，R.sub.6选择自氢、1至8个碳原子的烷基和2至8个碳原子的有机羧酸的酰基，以及它们的非毒性、药学上可接受的酸加合物和它们的与非毒性、药学上可接受的碱盐，具有显著的镇痛活性、极弱的抗炎活性和良好的胃肠系统耐受性，以及它们的制备和它们的中间体。
• Preparation of amides of 4-hydroxy-3-quinoline-carboxylic acid
  申请人：Roussel Uclaf

  公开号：US04596875A1

  公开（公告）日：1986-06-24

  Novel 4-hydroxy-3-quinoline-carboxamides of the formula ##STR1## wherein X is in the 5,6,7 or 8-position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --OCF.sub.3 and --SCF.sub.3, R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 is selected from the group consisting of thiazolyl, 4,5-dihydro-thiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidinyl and tetrazolyl, all optionally substituted with alkyl of 1 to 4 carbon atoms and phenyl optionally substituted with at least one member of the group consisting of --OH, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --NO.sub.2 and halogen, R.sub.3 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.4 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.5 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and ##STR2## R.sub.5 ' is selected from the group consisting of alkyl of 1 to 4 carbon atoms and aryl and their non-toxic, pharmaceutically acceptable acid addition salts and salts with non-toxic, pharmaceutically acceptable bases having very good analgesic activity and a non-negligible anti-inflammatory activity and novel intermediates.

  化合物的名称为4-羟基-3-喹啉甲酰胺，化学式如下：##STR1## 其中X位于5、6、7或8位，选自氢、卤素、1至5个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--OCF.sub.3和--SCF.sub.3的群组，R.sub.1选自氢和1至4个碳原子的烷基，R.sub.2选自噻唑基、4,5-二氢噻唑基、吡啶基、噁唑基、异噁唑基、咪唑基、嘧啶基和四唑基，均可选用1至4个碳原子的烷基和苯基，后者可选择至少一种取代基，所述取代基选自--OH、1至4个碳原子的烷基、1至4个碳原子的烷氧基、--CF.sub.3、--NO.sub.2和卤素的群组，R.sub.3选自氢、1至4个碳原子的烷基和芳基，R.sub.4选自氢、1至4个碳原子的烷基和芳基，R.sub.5选自氢、1至4个碳原子的烷基和##STR2##，R.sub.5'选自1至4个碳原子的烷基和芳基。该化合物及其中间体具有很好的镇痛活性和非常重要的抗炎活性，以及其非毒性、药学上可接受的酸盐和非毒性、药学上可接受的碱盐。