6-[(4-chloro-phenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-4-[3-[2-(dimethylamino)ethoxy]-phenyl]-1-methyl-2(1H)-quinolinone

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 6-[(4-chloro-phenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-4-[3-[2-(dimethylamino)ethoxy]-phenyl]-1-methyl-2(1H)-quinolinone
• 英文别名: (+/-)-6-[(4-chloro-phenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-4-[3-[2-(dimethylamino)ethoxy]-phenyl]-1-methyl-2(1H)-quinolinone；(+/-)-6-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-4-[3-[2-(dimethylamino)ethoxy]-phenyl]-1-methyl-2(1H)-quinolinone；6-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-4-[3-[2-(dimethylamino)ethoxy]-phenyl]-1-methyl-2(1H)-quinolinone；6-[(4-Chlorophenyl)-hydroxy-(3-methylimidazol-4-yl)methyl]-4-[3-[2-(dimethylamino)ethoxy]phenyl]-1-methylquinolin-2-one
• 化学式: C₃₁H₃₁ClN₄O₃
• 分子量: 543.065
• InChiKey: PLUXRLYRCFDZJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-[(4-chlorophenyl)-hydroxy-(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-hydroxyphenyl)-1-methyl-2(1H)-quinolinone 、 2-氯-N,N-二甲基乙胺 在 potassium carbonate 作用下， 以 二氯甲烷 、 2-氨基-3-氯-1,4-萘醌 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 以0.35 g (12%)的产率得到6-[(4-chloro-phenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-4-[3-[2-(dimethylamino)ethoxy]-phenyl]-1-methyl-2(1H)-quinolinone
  参考文献：
  名称：

  (Imidazol-5-yl)methyl-2-quinolinone derivatives as inhibitors of smooth muscle cell proliferation

  摘要：

  这项发明涉及使用式（I）的化合物，其中虚线代表可选键；X为氧或硫；R1为氢、C1-12烷基、Ar1、Ar2C1-6烷基、喹啉基C1-6烷基、吡啶基C1-6烷基、羟基C1-6烷基、C1-6烷氧基C1-6烷基、单烷基或双烷基胺基C1-6烷基、氨基C1-6烷基，或式—Alk1—C(=))—R9或—Alk1—S(O)2—R9的基团；R2、R3和R16各自独立地为氢、羟基、卤素、氰基、C1-6烷基、C1-6烷氧基、羟基C1-6烷氧基、C1-6烷氧基C1-6烷氧基、氨基C1-6烷氧基、单烷基或双烷基胺基C1-6烷氧基、Ar1Ar2C1-6烷基、Ar2氧基、Ar2C1-6烷氧基、羟基羰基、C1-6烷氧羰基、三卤甲基、三卤甲氧基、C2-6烯基；R4和R5各自独立地为氢、卤素、Ar1、C1-6烷基、羟基C1-6烷基、C1-6烷氧基C1-6烷基、C1-6烷氧基、C1-6烷硫基、氨基、羟基羰基、C1-6烷氧羰基、C1-6烷硫基C1-6烷基或C1-6烷硫基C1-6烷基；R6和R7各自独立地为氢、卤素、氰基、C1-6烷基、4,4-二甲基噁唑基、C1-6烷氧基或Ar2氧基；R8为氢、C1-6烷基、氰基、羟基羰基、C1-6烷氧羰基、C1-6烷酰基C1-6烷基、氰基C1-6烷基、C1-6烷氧羰基C1-6烷基、羧基C1-6烷基、羟基C1-6烷基、氨基C1-6烷基、单烷基或双烷基胺基C1-6烷基、咪唑基、卤素C1-6烷基、C1-6烷氧基C1-6烷基、氨基羰基C1-6烷基，或式—O—R10、—S—R10、—N—R11R12的基团；R17为氢、卤素、氰基、C1-6烷基、C1-6烷氧羰基、Ar1；R18为氢、C1-6烷基、C1-6烷氧基或卤素；R19为氢或C1-6烷基；用于制造一种抑制平滑肌细胞增殖的药物。

  公开号：

  US06365600B1

文献信息

• Method of use of (imidazol-5-yl)methyl-2-quinolinone derivatives to inhibit smooth muscle cell proliferation
  申请人：——

  公开号：US20040198771A1

  公开（公告）日：2004-10-07

  This invention comprises the use of compounds of formula (I) 1 wherein the dotted line represents an optional bond; X is oxygen or sulfur; R 1 is hydrogen, C 1-12 alkyl, Ar 1 , Ar 2 C 1-6 alkyl, quinolinylC 1-6 alkyl, pyridylC 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, aminoC 1-6 alkyl, or a radical of formula —Alk 1 —C(═O)—R 9 , —Alk 1 —S(O)—R 9 or —Alk 1 —S(O) 2 —R 9 ; R 2 , R 3 and R 16 each independently are hydrogen, hydroxy, halo, cyano, C 1-6 alkyl, C 1-6 alkyloxy, hydroxyC 1-6 alkyloxy, C 1-6 alkyloxyC 1-6 alkyloxy, aminoC 1-6 alkyloxy, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyloxy, Ar 1 , Ar 2 C 1-6 alkyl, Ar 2 oxy, Ar 2 C 1-6 alkyloxy, hydroxycarbonyl, C 1-6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2-6 alkenyl; R 4 and R 5 each independently are hydrogen, halo, Ar 1 , C 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, C 1-6 alkyloxy, C 1-6 alkylthio, amino, hydroxycarbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylS(O)C 1-6 alkyl or C 1-6 alkylS(O) 2 C 1-6 alkyl; R 6 and R 7 each independently are hydrogen, halo, cyano, C 1-6 alkyl, 4,4-dimethyl-oxazolyl, C 1-6 alkyloxy or Ar 2 oxy; R 8 is hydrogen, C 1-6 alkyl, cyano, hydroxycarbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylcarbonylC 1-6 alkyl, cyanoC 1-6 alkyl, C 1-6 alkyloxycarbonylC 1-6 alkyl, carboxyC 1-6 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, imidazolyl, haloC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, aminocarbonylC 1-6 alkyl, or a radical of formula —O—R 10 , —S—R 10 , —N—R 11 R 12 ; R 17 is hydrogen, halo, cyano, C 1-6 alkyl, C 1-6 alkyloxycarbonyl, Ar 1 ; R 18 is hydrogen, C 1-6 alkyl, C 1-6 alkyloxy or halo; R 19 is hydrogen or C 1-6 alkyl; for the manufacture of a medicament to inhibit smooth muscle cell proliferation.

  本发明涉及化合物的使用，其化学式为（I）1，其中虚线代表可选键；X为氧或硫；R1为氢、C1-12烷基、Ar1、Ar2C1-6烷基、喹啉基C1-6烷基、吡啶基C1-6烷基、羟基C1-6烷基、C1-6烷氧基C1-6烷基、单或双（C1-6烷基）氨基C1-6烷基、氨基C1-6烷基，或式为—Alk1—C(═O)—R9、—Alk1—S(O)—R9或—Alk1—S(O)2—R9的基团；R2、R3和R16各自独立地为氢、羟基、卤、氰、C1-6烷基、C1-6烷氧基、羟基C1-6烷氧基、C1-6烷氧基C1-6烷氧基、氨基C1-6烷氧基、单或双（C1-6烷基）氨基C1-6烷氧基、Ar1、Ar2C1-6烷基、Ar2氧基、Ar2C1-6烷氧基、羟基羧基、C1-6烷氧羧基、三卤甲基、三卤甲氧基、C2-6烯基；R4和R5各自独立地为氢、卤、Ar1、C1-6烷基、羟基C1-6烷基、C1-6烷氧基C1-6烷基、C1-6烷氧基、C1-6烷硫基、氨基、羟基羧基、C1-6烷氧羧基、C1-6烷基S（O）C1-6烷基或C1-6烷基S（O）2C1-6烷基；R6和R7各自独立地为氢、卤、氰、C1-6烷基、4,4-二甲基-噁唑基、C1-6烷氧基或Ar2氧基；R8为氢、C1-6烷基、氰、羟基羧基、C1-6烷氧羧基、C1-6烷基羧基C1-6烷基、氰基C1-6烷基、C1-6烷氧羧基C1-6烷基、羧基C1-6烷基、羟基C1-6烷基、氨基C1-6烷基、单或双（C1-6烷基）氨基C1-6烷基、咪唑基、卤基C1-6烷基、C1-6烷氧基C1-6烷基、氨基羧基C1-6烷基，或式为—O—R10、—S—R10、—N—R11R12的基团；R17为氢、卤、氰、C1-6烷基、C1-6烷氧羧基、Ar1；R18为氢、C1-6烷基、C1-6烷氧基或卤；R19为氢或C1-6烷基；用于制造一种抑制平滑肌细胞增殖的药物。
• Farnesyl protein transferase inhibiting (imidazol-5-yl)methyl-2-quinolinone derivatives
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1162201A2

  公开（公告）日：2001-12-12

  This invention comprises the novel compounds of formula (I) wherein the dotted line represents an optional bond; X is oxygen or sulfur; R1 is hydrogen, C1-12alkyl, Ar1, Ar2C1-6alkyl, quinolinylC1-6alkyl, pyridylC1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, aminoC1-6alkyl, or a radical of formula -Alk1-C(=O)-R9, -Alk1-S(O)-R9 or - Alk1-S(O)2-R9; R2, R3 and R16 each independently are hydrogen, hydroxy, halo, cyano, C1-6alkyl, C1-6alkyloxy, hydroxyC1-6alkyloxy, C1-6alkyloxyC1-6alkyloxy, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, Ar1, Ar2C1-6alkyl, Ar2oxy, Ar2C1-6alkyloxy, hydroxycarbonyl, C1-6alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C2-6alkenyl; R4 and R5 each independently are hydrogen, halo, Ar1, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkyloxy, C1-6alkylthio, amino, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylS(0)C1-6alkyl or C1-6alkylS(O)2C1-6alkyl; R6 and R7 each independently are hydrogen, halo, cyano, C1-6alkyl, 4,4-dimethyl-oxazolyl, C1-6alkyloxy or Ar2oxy; R8 is hydrogen, C1-6alkyl, cyano, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonylC1-6alkyl, cyanoC1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, carboxyC1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, imidazolyl, haloC1-6alkyl, C1-6alkyloxyC1-6alkyl, aminocarbonylC1-6alkyl, or a radical of formula -O-R10, -S-R10, -N-R11R12; R17 is hydrogen, halo, cyano, C1-6alkyl, C1-6alkyloxycarbonyl, Ar1; R18 is hydrogen, C1-6alkyl, C1-6alkyloxy or halo; R19 is hydrogen or C1-6alkyl; having farnesyl transferase inhibiting activity; their preparation, compositions containing them and their use as a medicine.

  本发明包括式 (I) 的新型化合物 其中虚线代表任选键；X 是氧或硫；R1 是氢、C1-12烷基、Ar1、Ar2C1-6烷基、喹啉基 C1-6烷基、吡啶基 C1-6烷基、羟基 C1-6烷基、C1-6烷氧基 C1-6烷基、单-或二(C1-6烷基)氨基 C1-6烷基、氨基 C1-6烷基或式-Alk1-C(=O)-R9、-Alk1-S(O)-R9 或-Alk1-S(O)2-R9 的基；R2、R3 和 R16 各自独立地为氢、羟基、卤代、氰基、C1-6烷基、C1-6烷氧基、羟基 C1-6烷氧基、C1-6烷氧基 C1-6烷氧基、氨基 C1-6烷氧基、一或二（C1-6烷基）氨基 C1-6烷氧基、Ar1、Ar2C1-6烷基、Ar2oxy、Ar2C1-6烷氧基、羟基羰基、C1-6烷氧基羰基、三卤甲基、三卤甲氧基、C2-6烯基；R4 和 R5 各自独立地为氢、卤代、Ar1、C1-6烷基、羟基 C1-6烷基、C1-6烷氧基 C1-6烷基、C1-6烷氧基、C1-6烷硫基、氨基、羟基羰基、C1-6烷氧基羰基、C1-6烷基S(0)C1-6烷基或 C1-6烷基S(O)2C1-6烷基；R6 和 R7 各自独立地为氢、卤代、氰基、C1-6-烷基、4,4-二甲基恶唑基、C1-6-烷氧基或 Ar2oxy；R8 是氢、C1-6烷基、氰基、羟基羰基、C1-6烷氧基羰基、C1-6烷基羰基 C1-6烷基、氰基 C1-6烷基、C1-6烷氧基羰基 C1-6烷基、羧基 C1-6烷基、羟基 C1-6烷基氨基 C1-6烷基、单-或二(C1-6烷基)氨基 C1-6烷基、咪唑基、卤代 C1-6烷基、C1-6烷氧基 C1-6烷基、氨基羰基 C1-6烷基或式 -O-R10、-S-R10、-N-R11R12 的基；R17 是氢、卤代、氰基、C1-6烷基、C1-6烷氧基羰基、Ar1； R18 是氢、C1-6烷基、C1-6烷氧基或卤代；R19 是氢或 C1-6烷基；具有法尼基转移酶抑制活性；其制备方法、含有它们的组合物及其作为药物的用途。
• US6037350
  申请人：——

  公开号：——

  公开（公告）日：——
• FARNESYL PROTEIN TRANSFERASE INHIBITING (IMIDAZOL-5-YL)METHYL-2-QUINOLINONE DERIVATIVES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0865440B1

  公开（公告）日：2002-04-03
• (IMIDAZOL-5-YL)METHYL-2-QUINOLINONE DERIVATIVES AS INHIBITORS OF SMOOTH MUSCLE CELL PROLIFERATION
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0988038A1

  公开（公告）日：2000-03-29