4-(3-chlorophenyl)-6-[1-(4-chlorophenyl)-2-hydroxy-1-(1H-imidazol-1-yl)ethyl]-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: 4-(3-chlorophenyl)-6-[1-(4-chlorophenyl)-2-hydroxy-1-(1H-imidazol-1-yl)ethyl]-1-methyl-2(1H)-quinolinone
• 英文别名: 4-(3-Chlorophenyl)-6-[1-(4-chlorophenyl)-2-hydroxy-1-imidazol-1-ylethyl]-1-methylquinolin-2-one
• 化学式: C₂₇H₂₁Cl₂N₃O₂
• 分子量: 490.389
• InChiKey: NMHLBRAQOAZCOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  58.4
• 氢给体数：
  1
• 氢受体数：
  3

文献信息

• Farnesyl transferase inhibiting 2-quinolone derivatives
  申请人：Janssen Pharmaceutica N.V.

  公开号：EP1106610A1

  公开（公告）日：2001-06-13

  The present invention is concerned with compounds of formula (I), the stereoisomeric forms thereof and the pharmaceutically acceptable acid or base addition salts thereof, 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 and R3 each independently are hydrogen, hydroxy, halo, cyano, C1-6alkyl, C1-6alkyloxy, hydroxyC1- 6alkyloxy, C1-6alkyloxy-C1-6alkyloxy, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)aminoC1- 6alkyloxy, Ar1, Ar2C1-6alkyl, Ar2oxy, Ar2C1-6alkyl-oxy, hydroxycarbonyl, C1-6alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C2-6alkenyl; or when on adjacent positions R2 and R3 taken together may form a bivalent radical; R4 and R5 each independently are hydrogen, Ar1, C1-6alkyl, C1-6alkyloxy-C1-6alkyl, C1-6alkyloxy, C1-6alkylthio, amino, hydroxycarbonyl, C1-6alkyloxy-carbonyl, C1-6alkylS(O)C1-6alkyl or C1-6alkylS(O)2-C1-6alkyl; R6 and R7 each independently are hydrogen, halo, cyano, C1-6alkyl, C1-6alkyloxy or Ar2oxy; R8 is hydrogen, C1-6alkyl, cyano, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkyl-carbonylC1-6alkyl, cyanoC1-6alkyl, C1-6alkyloxy-carbonylC1-6alkyl, hydroxycarbonyl-C1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, haloC1-6alkyl, C1-6alkyloxy-C1-6alkyl, aminocarbonylC1-6alkyl, Ar1, Ar2C1-6alkyl-oxyC1-6alkyl, C1-6alkylthioC1-6alkyl; R10 is hydrogen, C1-6alkyl or halo; R11 is hydrogen or C1-6alkyl; having farnesyl transferase inhibiting activity; their preparation, compositions containing them and their use as a medicine.

  本发明涉及式（I）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和R3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、Ar2氧基、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；或当 R2 和 R3 位于相邻位置时，可共同形成二价基；R4 和 R5 各自独立地为氢、Ar1、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(O)C1-6烷基或 C1-6烷基S(O)2-C1-6烷基；R6 和 R7 各自独立地为氢、卤代、氰基、C1-6烷基、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、羟基羰基-C1-6烷基、羟基羰基-C1-6烷基、C1-6烷氧基-羰基-C1-6烷基或 Ar2oxy、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、卤代-C1-6烷基、C1-6烷氧基-C1-6烷基、氨基羰基-C1-6烷基、Ar1、Ar2C1-6烷基-氧基-C1-6烷基、C1-6烷基硫代-C1-6烷基；R10为氢、C1-6烷基或卤代；R11为氢或C1-6烷基；具有法尼基转移酶抑制活性；它们的制备、含有它们的组合物以及它们作为药物的用途。
• FARNESYL TRANSFERASE INHIBITING 2-QUINOLONE DERIVATIVES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1019395B1

  公开（公告）日：2002-01-30
• TREATMENT OF LYSOSOMAL STORAGE DISEASES
  申请人：Link Medicine Corporation

  公开号：EP2155197A2

  公开（公告）日：2010-02-24
• US5968952A
  申请人：——

  公开号：US5968952A

  公开（公告）日：1999-10-19
• [EN] TREATMENT OF LYSOSOMAL STORAGE DISEASES<br/>[FR] TRAITEMENT DES MALADIES DE SURCHARGE LYSOSOMALE
  申请人：LINK MEDICINE CORP

  公开号：WO2008112525A2

  公开（公告）日：2008-09-18

  (EN) Methods and compositions useful in the treatment or prevention of lysosomal storage diseases, such as Pompe's disease, Fabry's disease, Gaucher's disease, and Niemann-Pick disease, are provided. The treatment includes administering to a subject a farnesyl transferase inhibitor compound. The treatment may also include enzyme replacement therapy or gene therapy.(FR) Cette invention a trait à des procédés et des compositions utilisés dans le traitement ou la prévention des maladies de surcharge lysosomale, comme la maladie de Pompe, la maladie de Fabry, la maladie de Gaucher et la maladie de Niemann-Pick. Le traitement comprend l'administration chez un sujet d'un composé inhibiteur de farnésyl transférase. Le traitement peut également comprendre une enzymothérapie de remplacement ou une thérapie génique.