6-[chloro(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-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-[chloro(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone
• 英文别名: 4-(3-chlorophenyl)-6-[chloro-(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone；6-[chloro-(4-chlorophenyl)-(3-methylimidazol-4-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2-one
• 化学式: C₂₇H₂₀Cl₃N₃O
• 分子量: 508.834
• InChiKey: YZLVWLZRTCFGIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  38.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-[chloro(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone 生成 替吡法尼
  参考文献：
  名称：

  [EN] FARNESYL PROTEIN TRANSFERASE INHIBITING (IMIDAZOL-5-YL)METHYL-2-QUINOLINONE DERIVATIVES
  [FR] DERIVES DE LA (IMIDAZOL-5-YL)METHYL-2-QUINOLEINONE COMME INHIBITEUR DE LA PROTEINE FARNESYLE-TRANSFERASE

  摘要：

  该发明涉及公式（I）的新化合物，其中虚线表示可选键；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，或公式-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烷基硫基，氨基，羟基羰基，C1-6烷氧羰基，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烷基羰基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，单或双（C1-6烷基）氨基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，或公式-O-R10，-S-R10，-N-R11R12的基团；R17为氢，卤素，氰基，C1-6烷基，C1-6烷氧基羰基，Ar1；R18为氢，C1-6烷基，C1-6烷氧基或卤素；R19为氢或C1-6烷基；具有法尼酰转移酶抑制活性；它们的制备，含有它们的组合物以及它们作为药物的用途。

  公开号：

  WO1997021701A1
• 作为产物：
  描述：

  4-(3-chlorophenyl)-6-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone 生成 6-[chloro(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone
  参考文献：
  名称：

  [EN] FARNESYL PROTEIN TRANSFERASE INHIBITING (IMIDAZOL-5-YL)METHYL-2-QUINOLINONE DERIVATIVES
  [FR] DERIVES DE LA (IMIDAZOL-5-YL)METHYL-2-QUINOLEINONE COMME INHIBITEUR DE LA PROTEINE FARNESYLE-TRANSFERASE

  摘要：

  该发明涉及公式（I）的新化合物，其中虚线表示可选键；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，或公式-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烷基硫基，氨基，羟基羰基，C1-6烷氧羰基，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烷基羰基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，单或双（C1-6烷基）氨基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，或公式-O-R10，-S-R10，-N-R11R12的基团；R17为氢，卤素，氰基，C1-6烷基，C1-6烷氧基羰基，Ar1；R18为氢，C1-6烷基，C1-6烷氧基或卤素；R19为氢或C1-6烷基；具有法尼酰转移酶抑制活性；它们的制备，含有它们的组合物以及它们作为药物的用途。

  公开号：

  WO1997021701A1

文献信息

• [EN] DIASTEREOSELECTIVE SYNTHESIS PROCESS FOR THE PREPARATION OF IMIDAZOLE COMPOUNDS<br/>[FR] PROCEDE DE SYNTHESE DIASTEREOSELECTIVE POUR LA PREPARATION DE COMPOSES IMIDAZOLE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2005105784A1

  公开（公告）日：2005-11-10

  A diastereoselective synthesis process for the preparation of an enantiomer of 6-­[amino(4-chlorophenyl)(1-methyl-1 H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)- 1-­methyl-2(1H)-quinolinone which comprises the conversion of (±)-6-[chloro(4­-chlomphenyl)(I-methyl-lH-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl­2(IH)-quinolinone into a compound of formula (VIII) wherein aryl is phenyl substituted once or twice with C1-6alkyloxy or naphtalenyl substituted once or twice with Cl-6alkyloxy.

  一种对映选择性合成过程，用于制备6-[氨基(4-氯苯基)(1-甲基-1H-咪唑-5-基)甲基]-4-(3-氯苯基)-1-甲基-2(1H)-喹啉酮的对映异构体，包括将(±)-6-[氯(4-氯苯基)(1-甲基-1H-咪唑-5-基)甲基]-4-(3-氯苯基)-1-甲基-2(1H)-喹啉酮转化为式(VIII)的化合物，其中芳基是苯基，一次或两次用C1-6烷氧基取代，或者是萘基，一次或两次用C1-6烷氧基或Cl-6烷氧基取代。
• [EN] DIASTEREOSELECTIVE SYNTHESIS PROCESS WITH 6-BROMO-4-(3-CHLOROPHENYL)-2-METHOXY-QUINOLINE<br/>[FR] PROCEDE DE SYNTHESE DIASTEREOSELECTIF UTILISANT LA 6-BROMO-4-(3-CHLOROPHENYL)-2-METHOXY-QUINOLINE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2005105783A1

  公开（公告）日：2005-11-10

  A diastereoselective synthesis process for the preparation of (R)-(+)- 6-[amino(4­chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl­2(IH)-quinolinone which comprises the preparation of a compound of formula (XVII) : and the stereochemically isomeric forms thereof wherein R is C1-6alkyl or C1-6alkylphenyl-.

  一种具有对映选择性的合成过程，用于制备(R)-(+)-6-[氨基(4-氯苯基)(1-甲基-1H-咪唑-5-基)甲基]-4-(3-氯苯基)-1-甲基-2(IH)-喹啉酮，其中包括制备化合物XVII的过程：以及其立体化学异构体，其中R为C1-6烷基或C1-6烷基苯基。
• [EN] FARNESYL PROTEIN TRANSFERASE INHIBITING (IMIDAZOL-5-YL)METHYL-2-QUINOLINONE DERIVATIVES<br/>[FR] DERIVES DE LA (IMIDAZOL-5-YL)METHYL-2-QUINOLEINONE COMME INHIBITEUR DE LA PROTEINE FARNESYLE-TRANSFERASE
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1997021701A1

  公开（公告）日：1997-06-19

  (EN) 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(O)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.(FR) L'invention concerne de nouveaux composés de la formule générale (I). Dans cette formule, la ligne en pointillé représente une liaison facultative; X est oxygène ou soufre; R1 est un hydrogène, C1-12alkyle, Ar1, Ar2C1-6alkyle, quinoléinylC1-6alkyle, pyridiylC1-6alkyle, hydroxyC1-6alkyle, C1-6alkyloxyC1-6alkyle, mono- or di(C1-6alkyl)aminoC1-6alkyle, amino C1-6alkyle, un radical de la formule -Alk1-C(=O)-R9, Alk1-S(O)-R9 ou -Alk1-S(O)2-R9; R2, R3 et R16 sont chacun d'une manière indépendante un hydrogène, hydroxy, halo, cyano, C1-6alkyle, C1-6alkyloxy, hydroxyC1-6alkyloxy, C1-6alkyloxyC1-6alkyloxy, aminoC1-6alkyloxy, mono- ou di(C1-6alkyl)aminoC1-6alkyloxy, Ar1, Ar2C1-6alkyle, Ar2oxy, Ar2C1-6alkyloxy, hydroxycarbonyle, C1-6alkyloxycarbonyle, trihalométhyle, trihalométhoxy, C2-6alcényle; R4 et R5 sont chacun d'une manière indépendante un hydrogène, halo, Ar1, C1-6alkyle, hydroxyC1-6alkyle, C1-6alkyloxyC1-6alkyle, C1-6alkyloxy, C1-6alkylthio, amino, hydroxycarbonyle, C1-6alkyloxycarbonyle, C1-6alkylS(O)C1-6alkyle ou C1-6alkyl-S(O)2C1-6alkyle; R6 et R7 sont chacun d'une manière indépendante un hydrogène, halo, cyano, C1-6alkyle, 4,4-diméthyl-oxyzolyl, C1-6alkyloxy ou Ar2oxy; R8 is hydrogène, C1-6alkyle, cyano, hydroxycarbonyle, C1-6alkyloxycarbonyle, C1-6alkylcarbonylC1-6alkyle, cyanoC1-6alkyle, C1-6alkyloxycarbonylC1-6alkyle, carboxyC1-6alkyle, hydroxyC1-6alkyle, aminoC1-6alkyle, mono- ou di(C1-6alkyl)aminoC1-6alkyle, imidazolyl, haloC1-6alkyle, C1-6alkyloxyC1-6alkyle, aminocarbonylC1-6alkyle, ou un radical de la formule -O-R10, -S-R10, -N-R11R12; R17 est un hydrogène, halo, cyano, C1-6alkyle, C1-6alkyloxycarbonyle, Ar1; R18 est un hydrogène, C1-6alkyle, C1-6alkyloxy ou halo; R19 est un hydrogène ou C1-6alkyle. Ces composés sont des inhibiteurs de la protéine farnésyle transférase. L'invention concerne également la préparation de ces composés, des compositions les contenant et leur utilisation en médecine.

  该发明涉及公式（I）的新化合物，其中虚线表示可选键；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，或公式-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烷基硫基，氨基，羟基羰基，C1-6烷氧羰基，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烷基羰基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，单或双（C1-6烷基）氨基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，或公式-O-R10，-S-R10，-N-R11R12的基团；R17为氢，卤素，氰基，C1-6烷基，C1-6烷氧基羰基，Ar1；R18为氢，C1-6烷基，C1-6烷氧基或卤素；R19为氢或C1-6烷基；具有法尼酰转移酶抑制活性；它们的制备，含有它们的组合物以及它们作为药物的用途。
• Process for the preparation of imidazole compounds
  申请人：——

  公开号：US20040138256A1

  公开（公告）日：2004-07-15

  A process for the preparation of 4-(3-chlorophenyl)-6-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone which comprises reacting 6-(4-chlorobenzoyl)-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone with a C 6-8 alkyllithium compound, 1-methylimidazole and a tri(C 4-6 alkyl)silyl halide to obtain better yields of the above product.

  制备4-(3-氯苯基)-6-[(4-氯苯基)羟基(1-甲基-1H-咪唑-5-基)甲基]-1-甲基-2(1H)-喹啉酮的方法，包括将6-(4-氯苯甲酰基)-4-(3-氯苯基)-1-甲基-2(1H)-喹啉酮与C6-8烷基锂化合物、1-甲基咪唑和三(C4-6烷基)硅基卤化物反应，以获得上述产物的更好产率。
• Diastereoselective Synthesis Process for the Preparation of Imidazole Compounds
  申请人：Filliers Ferdinand Maria Walter

  公开号：US20070238880A1

  公开（公告）日：2007-10-11

  A diastereoselective synthesis process for the preparation of an enantiomer of 6-[amino(4-chlorophenyl)(1-methyl-1 H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone which comprises the conversion of (±)-6-[chloro(4 -chlomphenyl)(I-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl2(IH)-quinolinone into a compound of formula (VIII) wherein aryl is phenyl substituted once or twice with C 1-6 alkyloxy or naphtalenyl substituted once or twice with C 1-6 alkyloxy.

  一种对映异构体的对映选择性合成过程，用于制备6-[氨基(4-氯苯基)(1-甲基-1H-咪唑-5-基)甲基]-4-(3-氯苯基)-1-甲基-2(1H)-喹啉酮的对映异构体，其包括将(±)-6-[氯(4-氯苯基)(1-甲基-1H-咪唑-5-基)甲基]-4-(3-氯苯基)-1-甲基2(1H)-喹啉酮转化为化合物(VIII)，其中芳基是苯基，一次或两次用C1-6烷氧基取代，或者是萘基，一次或两次用C1-6烷氧基取代。