2-(1-chloro-2-methylpropyl)-8-(trifluoromethyl)-4H-3,1-benzoxazin-4-one | 114351-22-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 2-(1-chloro-2-methylpropyl)-8-(trifluoromethyl)-4H-3,1-benzoxazin-4-one
• 英文别名: 2-(1-chloro-2-methylpropyl)-8-trifluoromethyl-4H-3,1-benzoxazine-4-one；2-(1-chloro-2-methylpropyl)-8-(trifluoromethyl)-3,1-benzoxazin-4-one
• CAS: 114351-22-3
• 化学式: C₁₃H₁₁ClF₃NO₂
• 分子量: 305.684
• InChiKey: KTGGTCZOMXWBAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(1-chloro-2-methylpropyl)-8-(trifluoromethyl)-4H-3,1-benzoxazin-4-one 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 16.0h， 生成 1,3-dihydro-3-(1-methylethyl)-1-[(2-pyridinyl)-imino]-5-trifluoromethyl furo[3,4-b]-quinolin-9-ol
  参考文献：
  名称：

  具有抗关节炎和止痛作用的4-羟基-3-喹啉甲酰胺。

  摘要：

  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。

  DOI：

  10.1021/jm00402a034
• 作为产物：
  描述：

  2-氨基-3-(三氟甲基)苯甲酸 以78%的产率得到
  参考文献：
  名称：

  CLEMENCE, FRANCOIS;LE, MARTRET ODILE;DELEVALLEE, FRANCOISE;BENZONI, JOSET+, J. MED. CHEM., 31,(1988) N 7, C. 1453-1462

  摘要：

  DOI：

文献信息

• Analgesic and anti-inflammatory 4-OH quinoline carboxylic acid
  申请人：Roussel Uclaf

  公开号：US04988708A1

  公开（公告）日：1991-01-29

  A compound selected from the group consisting of optical isomers and racemates of 4-hydroxy-3-quinoline carboxylates 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, --SCF.sub.3, and OCF.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-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl and tetrazolyl, all optionally substituted with alkyl of 1 to 4 carbon atoms and phenyl and phenyl substituted with at least one member of the group consisting of --OH, alkyl and alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --NO.sub.2 and halogen, A is ##STR2## in which R.sub.3 and R.sub.4 are individually selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.5 is heteroaryl f 3 to 14 carbon atoms optionally substituted with alkyl of 1 to 4 carbon atoms and their non-toxic, pharmaceutically acceptable salts with acids or bases having analgesic and anti-inflammatory activity.

  从由光学异构体和4-羟基-3-喹啉羧酸酯的拉氏体组成的群体中选择的一种化合物，其化学式为##STR1##其中X位于第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、--SCF.sub.3和OCF.sub.3的群体，R.sub.1选自氢和1至4个碳原子的烷基的群体，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、嘧啶基和四唑基的群体，所有这些基都可以用1至4个碳原子的烷基和苯基以及苯基替代物中的至少一个成员替代，这些苯基替代物包括--OH、烷基和1至4个碳原子的烷氧基、--CF.sub.3、--NO.sub.2和卤素，A为##STR2##其中R.sub.3和R.sub.4分别选自氢、1至4个碳原子的烷基和芳基，R.sub.5为异芳基，含有3至14个碳原子，可选地用1至4个碳原子的烷基替代，以及其与酸或碱形成的无毒、药用可接受的盐，具有镇痛和抗炎活性。
• Novel 4-hydroxy-3-quinoline-carboxylates having analgesic and
  申请人：Roussel Uclaf

  公开号：US04735951A1

  公开（公告）日：1988-04-05

  Novel optical isomers and racemates of 4-hydroxy-3-quinoline-carboxylates 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, --SCF.sub.3 and --OCF.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-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl and tetrazolyl all optionally substituted with alkyl of 1 to 4 carbon atoms and phenyl substituted with at least one member of the group consisting of --OH, alkyl and alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --NO.sub.2 and halogen, R.sub.3 and R.sub.4 are individually 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 aryl of 6 to 14 carbon atoms, heteroaryl of 3 to 14 carbon atoms, alkyl of 1 to 14 carbon atoms, alkyl substituted with --NH.sub.2, --NHAlk or ##STR2## alkenyl of 2 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms substituted with aryl of 6 to 14 carbon atoms, Alk and Alk' are alkyl of 1 to 6 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts with the proviso that when X is 8-CF.sub.3, R.sub.1 and R.sub.3 are hydrogen, R.sub.2 is 2-thiazolyl, R.sub.4 is methyl, R.sub.5 is not methyl having analgesic and anti-inflammatory activity.

  新型光学异构体和4-羟基-3-喹啉羧酸酯的拉氨酸盐的分子式如下：其中X位于第5、6、7或8位置，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、--SCF.sub.3和--OCF.sub.3的组成群，R.sub.1选择自氢和1至4个碳原子的烷基，R.sub.2选择自噻唑基、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，所有这些基都可以选择性地用1至4个碳原子的烷基取代，以及至少一个成员取代的苯基，该成员由--OH、1至4个碳原子的烷基和烷氧基、--CF.sub.3、--NO.sub.2和卤素组成，R.sub.3和R.sub.4分别选择自氢、1至4个碳原子的烷基和芳基，R.sub.5选择自6至14个碳原子的芳基、3至14个碳原子的杂环芳基、1至14个碳原子的烷基、烷基取代的--NH.sub.2、--NHAlk或##STR2##、2至6个碳原子的烯基、2至6个碳原子的烯基取代的6至14个碳原子的芳基，Alk和Alk'为1至6个碳原子的烷基，以及它们的无毒、药学上可接受的酸盐，条件是当X为8-CF.sub.3时，R.sub.1和R.sub.3为氢，R.sub.2为2-噻唑基，R.sub.4为甲基，R.sub.5不是甲基，具有镇痛和抗炎活性。
• 4-OH-quinoline carboxylic acid amides having analgesic and
  申请人：Roussel Uclaf

  公开号：US04845105A1

  公开（公告）日：1989-07-04

  A compound selected from the group consisting of optical isomers and racemates of 4-hydroxy-3-quinoline carboxylates 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, --SCF.sub.3 and --OCF.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-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl and tetrazolyl, all optionally substituted with alkyl of 1 to 4 carbon atoms and phenyl and phenyl substituted with at least one member of the group consisting of --OH, alkyl and alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --NO.sub.2 and halogen, A is either ##STR2## in which R.sub.3 and R.sub.4 are individually 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 aryl of 6 to 14 carbon atoms, heteroaryl of 3 to 14 carbon atoms, alkyl of 1 to 14 carbon atoms, alkyl substituted with --NH.sub.2, --NHAlk or ##STR3## alkenyl of 2 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms substituted with aryl of 6 to 14 carbon atoms, Alk and Alk' are alkyl of 1 to 6 carbon atoms or, when R.sub.1 is hydrogen, A is ##STR4## and R.sub.3a are individually selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, aryl and ##STR5## or R.sub.2a and R.sub.3a together form acetonide, R.sub.4a is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and aryl, R.sub.5a is selected from the group consisting of alkyl of 1 to 4 carbon atoms and aryl with the proviso that when X is 8--CF.sub.3, R.sub.1 and R.sub.3 are hydrogen, R.sub.2 is 2-thiazolyl, R.sub.4 is methyl, R.sub.5 is not methyl and their non-toxic, pharmaceutically acceptable salts with acids or bases having analgesic and anti-inflammatory activity.

  从由光学异构体和4-羟基-3-喹啉羧酸酯的拉克酸盐中选择的化合物，其化学式为##STR1##其中X位于5、6、7或8位置，选择自氢、卤素、碳原子数为1到5的烷基、碳原子数为1到4的烷氧基、--CF.sub.3、--SCF.sub.3和--OCF.sub.3的群组中，R.sub.1选择自氢和碳原子数为1到4的烷基，R.sub.2选择自噻唑基、4,5-二氢噻唑基、吡啶基、噁唑基、异噁唑基、咪唑基、嘧啶基和四唑基的群组中，所有这些基都可以用碳原子数为1到4的烷基和苯基以及苯基上至少一个成员的群组--OH、烷基和碳原子数为1到4的烷氧基、--CF.sub.3、--NO.sub.2和卤素进行取代，A可以是##STR2##其中R.sub.3和R.sub.4分别选择自氢、碳原子数为1到4的烷基和芳基，R.sub.5选择自碳原子数为6到14的芳基、碳原子数为3到14的杂环芳基、碳原子数为1到14的烷基、烷基取代--NH.sub.2、--NHAlk或##STR3##烯基取代为6到14碳原子的芳基、Alk和Alk'为碳原子数为1到6的烷基或者当R.sub.1为氢时，A为##STR4##并且R.sub.3a和R.sub.4a分别选择自氢、碳原子数为1到4的烷基、芳基和##STR5##或者R.sub.2a和R.sub.3a一起形成缩醛，R.sub.4a选择自氢、碳原子数为1到4的烷基和芳基，R.sub.5a选择自碳原子数为1到4的烷基和芳基，但如果X为8--CF.sub.3，R.sub.1和R.sub.3为氢，R.sub.2为2-噻唑基，R.sub.4为甲基，R.sub.5不是甲基，以及它们的无毒、药用可接受的酸或碱盐，具有镇痛和抗炎活性。
• Alkyl .beta.-oxo-benzenepropanoates
  申请人：Uclaf; Roussel

  公开号：US04687857A1

  公开（公告）日：1987-08-18

  Novel alkyl .beta.-oxo-benzenepropanoates 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 --, CF.sub.3 S-- and CF.sub.3 O--, 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, thiazolyl, 4,5-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl, tetrazolyl, thienyl, benzothiazolyl and phenyl optionally substituted with at least one member of the group consisting of halogen, alkoxy of 1 to 4 carbon atoms, hydroxy, phenyl, CF.sub.3 --, NO.sub.2 -- alkyl of 1 to 4 carbon atoms and alkyl of 1 to 4 carbon atoms substituted with amino, alkylamino or dialkylamino with alkyls of 1 to 3 carbon atoms or R.sub.1 ' and R.sub.2 ' taken together with the nitrogen atom to which they are attached form a member of the group consisting of thiazolyl, 4,5-dihydrothiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidyl, tetrazolyl, thienyl and benzothiazolyl with the double bond being attached to the nitrogen atom, R is alkyl of 1 to 8 carbon atoms, R.sub.3 is selected from the group consisting of hydrogen, halogen and alkyl of 1 to 4 carbon atoms, R.sub.4 is hydrogen or halogen and R.sub.5 is halogen and a process for their preparation and a process for the preparation of compounds of the formula ##STR2## wherein X, R.sub.1 ', R.sub.2 ', R.sub.3, R.sub.4 and R.sub.5 have the above definition.

  该专利描述了一种化合物，化学式为##STR1##，其中X位于5、6、7或8位置，并从氢、卤素、1到5个碳原子的烷基、1到4个碳原子的烷氧基、CF.sub.3 --、CF.sub.3 S--和CF.sub.3 O--中选择，R.sub.1'从氢和1到4个碳原子的烷基中选择，R.sub.2'从氢、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、四唑基、噻吩基、苯并噻唑基和苯基中选择，所述苯基可以选择至少一个来自卤素、1到4个碳原子的烷氧基、羟基、苯基、CF.sub.3 --、NO.sub.2 --、1到4个碳原子的烷基和带有1到3个碳原子的烷基、氨基取代的1到4个碳原子的烷基或二烷基氨基的烷基取代物，或者R.sub.1'和R.sub.2'与它们连接的氮原子一起形成噻唑基、4,5-二氢噻唑基、吡啶基、噁唑基、异噁唑基、咪唑基、嘧啶基、四唑基、噻吩基和苯并噻唑基，双键连接到氮原子上，R为1到8个碳原子的烷基，R.sub.3从氢、卤素和1到4个碳原子的烷基中选择，R.sub.4为氢或卤素，R.sub.5为卤素。此外，该专利还包括制备该化合物的方法以及化学式##STR2##中X、R.sub.1'、R.sub.2'、R.sub.3、R.sub.4和R.sub.5的定义。
• ——
  作者：CLEMENCE F.、 LE MARTRET O.、 DELEVALLEE F.

  DOI：——

  日期：——