3-Butyryl-4-(2-methylphenylamino)-8oxiranylquinoline | 135385-24-9

• 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: 3-Butyryl-4-(2-methylphenylamino)-8oxiranylquinoline
• 英文别名: 1-[4-(2-methylanilino)-8-(oxiran-2-yl)quinolin-3-yl]butan-1-one
• CAS: 135385-24-9
• 化学式: C₂₂H₂₂N₂O₂
• 分子量: 346.429
• InChiKey: LJIQDGLAGAIPTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-Butyryl-4-(2-methylphenylamino)-8oxiranylquinoline 、 吗啉 在 1,4-二氧六环 、 乙酸乙酯 、 Brine 、 乙醚 、 methylene chloride diethyl ether 作用下， 以 1,4-二氧六环 为溶剂， 反应 9.0h， 以gave 3-butyryl-4-(2-methylphenylamino)-8-(1-hydroxy-2-morpholinoethyl)quinoline (0.59 g, 47%), m.p. 135°-137°的产率得到3-butyryl-4-(2-methylphenylamino)-8-(1-hydroxy-2-morpholinoethyl)quinoline
  参考文献：
  名称：

  3-carbonyl-4-amino-8-substituted quinoline compounds useful in

  摘要：

  氨基喹啉衍生物被描述为抑制H.sup.+ K.sup.+ ATPase酶的药物，可用于治疗胃酸过多。该发明的化合物是3-丁酰基-4-(2-甲基苯胺)-8-(3-二甲氨基丙氧基)喹啉。

  公开号：

  US05082841A1
• 作为产物：
  描述：

  3-butyryl-4-(2-methylphenylamino)-8-(hydroxymethyl)quinoline 在 sodium hydroxide 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 3-Butyryl-4-(2-methylphenylamino)-8oxiranylquinoline
  参考文献：
  名称：

  Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 4. Identification of an Inhibitor with an Intermediate Duration of Action

  摘要：

  3-Acyl-4-(arylamino)quinolines were previously identified as gastric (H+/K+)-ATPase inhibitors, and clinical efficacy has been demonstrated for compound 3 (SK&F 96067). In the present study the further structure-activity relationship of this series is developed. Only a limited range of substituents are tolerated on the N-aryl ring or the 6- and 7-positions of the quinoline, and although hydroxylated derivatives were identified possessing markedly greater affinity for the enzyme, none of these proved to have adequate potency after oral dosing. In contrast, the 8-position of the quinoline ring proved suitable for a wide variety of substituents, allowing modification of physicochemical properties while retaining primary activity. This led to the identification of compound 4 (SK&F 97574), which combines good oral potency with a somewhat longer duration of action than 3 (though much shorter than covalent inhibitors such as omeprazole). This compound was selected for further development and evaluation in man.

  DOI：

  10.1021/jm00014a026

文献信息

• 3-carbonyl-4-amino-8-substituted quinoline compounds useful in
  申请人：SmithKline Beecham Intercredit B.V.

  公开号：US05082841A1

  公开（公告）日：1992-01-21

  Aminoquinoline derivatives are described as inhibitors of the H.sup.+ K.sup.+ ATPase enzyme useful in the treatment of gastric acidity. A compound of the invention is 3-butyryl-4-(2-methylphenylamino)-8-(3-dimethylaminopropoxy)quinoline.

  氨基喹啉衍生物被描述为抑制H.sup.+ K.sup.+ ATPase酶的药物，可用于治疗胃酸过多。该发明的化合物是3-丁酰基-4-(2-甲基苯胺)-8-(3-二甲氨基丙氧基)喹啉。
• Substituted 4-aminoquinolines
  申请人：SMITHKLINE BEECHAM INTERCREDIT B.V.

  公开号：EP0416749A2

  公开（公告）日：1991-03-13

  Compounds of structure: in which Ar is a phenyl group optionally substituted by 1 to 3 substituents selected from C1-6alkyl, C1-6alkoxy, amino, C1-6-alkylthio, halogen, cyano, hydroxy, carbamoyl, carboxy, C1-6alkanoyl or trifluoromethyl; n is 0 to 4; R1 is hydrogen or C1-6alkyl; R2 is hydrogen, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6-alkyl, C3-scycloalkyl, C3-6cycloalkylC1-6alkyl, phenyl, phenylC1-6alkyl, the phenyl groups being optionally substituted; X is a bond, CHOH, NR1, S, or O; p is 1 to 6; and R3 and R4 are the same or different and are each hydrogen, C1-4alkyl, or optionally substituted phenylC1 -4alkyl or together with the nitrogen atom to which they are attached form a ring, optionally containing one or more further heteroatoms, or a salt thereof, processes for their preparation, pharmaceutical compositions containing them, and their use in therapy.

  结构的化合物： 其中 Ar 是苯基，可任选被 1 至 3 个取代基取代，这些取代基选自 C1-6-烷基、C1-6-烷氧基、氨基、C1-6-烷硫基、卤素、氰基、羟基、氨基甲酰基、羧基、C1-6-烷酰基或三氟甲基； n 为 0 至 4； R1 是氢或 C1-6 烷基； R2 是氢、C1-6-烷基、C1-6-烷氧基、C1-6-烷氧基 C1-6-烷基、C3-环烷基、C3-6-环烷基 C1-6-烷基、苯基、苯基 C1-6-烷基，苯基基团被任选取代； X 是键、CHOH、NR1、S 或 O； p 是 1 至 6；以及 R3 和 R4 相同或不同，各自为氢、C1-4 烷基或任选取代的苯基 C1-4 烷基，或与所连接的氮原子一起形成环，任选含有一个或多个杂原子，如 或其盐 或它们的盐、它们的制备工艺、含有它们的药物组合物以及它们在治疗中的用途。
• US5082841A
  申请人：——

  公开号：US5082841A

  公开（公告）日：1992-01-21
• Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 4. Identification of an Inhibitor with an Intermediate Duration of Action
  作者：Colin A. Leach、Thomas H. Brown、Robert J. Ife、David J. Keeling、Michael E. Parsons、Colin J. Theobald、Kenneth J. Wiggall

  DOI：10.1021/jm00014a026

  日期：1995.7

  3-Acyl-4-(arylamino)quinolines were previously identified as gastric (H+/K+)-ATPase inhibitors, and clinical efficacy has been demonstrated for compound 3 (SK&F 96067). In the present study the further structure-activity relationship of this series is developed. Only a limited range of substituents are tolerated on the N-aryl ring or the 6- and 7-positions of the quinoline, and although hydroxylated derivatives were identified possessing markedly greater affinity for the enzyme, none of these proved to have adequate potency after oral dosing. In contrast, the 8-position of the quinoline ring proved suitable for a wide variety of substituents, allowing modification of physicochemical properties while retaining primary activity. This led to the identification of compound 4 (SK&F 97574), which combines good oral potency with a somewhat longer duration of action than 3 (though much shorter than covalent inhibitors such as omeprazole). This compound was selected for further development and evaluation in man.