6-(4-氯苯甲酰)-4-(3-氯苯基)喹啉-2(1H)-酮 | 192187-32-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 中文名称: 6-(4-氯苯甲酰)-4-(3-氯苯基)喹啉-2(1H)-酮
• 英文名称: R101763
• 英文别名: 6-(4-chlorobenzoyl)-4-(3-chlorophenyl)-2(1H)-quinolinone；4-(3-chlorophenyl)-6-(4-chlorobenzoyl)-2-quinolinone；6-(4-Chloro-benzoyl)-4-(3-chloro-phenyl)-1H-quinolin-2-one；6-(4-chlorobenzoyl)-4-(3-chlorophenyl)-1H-quinolin-2-one
• CAS: 192187-32-9
• 化学式: C₂₂H₁₃Cl₂NO₂
• 分子量: 394.257
• InChiKey: ZLYWVUYGARBCQN-UHFFFAOYSA-N

物化性质

• 熔点：
  230-235 °C
• 沸点：
  624.7±55.0 °C(Predicted)
• 密度：
  1.377±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-(4-氯苯甲酰)-4-(3-氯苯基)喹啉-2(1H)-酮 在 甲醇 、 sodium hydroxide 、 氯化亚砜 、 三异丁基氯硅烷 、 苄基三乙基氯化铵 、 氨 、 正己基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 38.25h， 生成 6-[氨基-(4-氯苯基)-(3-甲基咪唑-4-基)甲基]-4-(3-氯苯基)-1-甲基喹啉-2-酮
  参考文献：
  名称：

  法呢基蛋白转移酶抑制剂 ZARNESTRATM 的合成路线

  摘要：

  Ras 癌蛋白的翻译后法呢基化是发挥其生物学效应的重要步骤，这一发现导致了法呢基蛋白转移酶抑制剂 (FTI) 的设计，以控制带有 Ras 突变的肿瘤的生长。对小鼠模型的临床前研究证实了它们对肿瘤生长的抑制作用并促进了临床开发。R115777 (ZARNESTRATM) 目前正在进行临床评估，最近的研究证实了其抗肿瘤潜力和低毒性。我们希望在此描述我们团队开发的用于访问 ZARNESTRATM 的化学合成路线。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

  DOI：

  10.1002/ejoc.200300538
• 作为产物：
  描述：

  4-氯-4-硝基苯甲酮 在 sodium hydroxide 、 potassium tert-butylate 、 三氯化钛 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 甲苯 为溶剂， 反应 64.0h， 生成 6-(4-氯苯甲酰)-4-(3-氯苯基)喹啉-2(1H)-酮
  参考文献：
  名称：

  法呢基蛋白转移酶抑制剂 ZARNESTRATM 的合成路线

  摘要：

  Ras 癌蛋白的翻译后法呢基化是发挥其生物学效应的重要步骤，这一发现导致了法呢基蛋白转移酶抑制剂 (FTI) 的设计，以控制带有 Ras 突变的肿瘤的生长。对小鼠模型的临床前研究证实了它们对肿瘤生长的抑制作用并促进了临床开发。R115777 (ZARNESTRATM) 目前正在进行临床评估，最近的研究证实了其抗肿瘤潜力和低毒性。我们希望在此描述我们团队开发的用于访问 ZARNESTRATM 的化学合成路线。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

  DOI：

  10.1002/ejoc.200300538

文献信息

• Practical Route to 2-Quinolinones via a Pd-Catalyzed C–H Bond Activation/C–C Bond Formation/Cyclization Cascade Reaction
  作者：Junliang Wu、Shaohua Xiang、Jing Zeng、Minli Leow、Xue-Wei Liu

  DOI：10.1021/ol503292p

  日期：2015.1.16

  Quinolinone derivatives were constructed via a Pd-catalyzed C–H bond activation/C–C bond formation/cyclization cascade process with simple anilines as the substrates. This finding provides a practical procedure for the synthesis of quinolinone-containing alkaloids and drug molecules. The utility of this method was demonstrated by a formal synthesis of Tipifarnib.

  喹啉酮衍生物是通过Pd催化的C–H键活化/ CC键形成/环化级联过程构建的，并以简单的苯胺为底物。该发现为合成含喹啉酮的生物碱和药物分子提供了实用的程序。蒂法法尼的正式合成证明了该方法的实用性。
• Farnesyl transferase inhibiting 2-quinolone derivatives
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US05968952A1

  公开（公告）日：1999-10-19

  The present invention is concerned with compounds of formula (I), ##STR1## 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; R.sup.1 is hydrogen, C.sub.1-12 alkyl, Ar.sup.1, Ar.sup.2 C.sub.1-6 alkyl, quinolinylC.sub.1-6 alkyl, pyridylC.sub.1-6 alkyl, hydroxyC.sub.1-6 alkyl, C.sub.1-6 alkyloxyC.sub.1-6 alkyl, mono- or di(C.sub.1-6 alkyl)-aminoC.sub.1-6 alkyl, aminoC.sub.1-6 alkyl, or a radical of formula --Alk.sup.1 --C(.dbd.O)--R.sup.9, --Alk.sup.1 --S(O)--R.sup.9 or --Alk.sup.1 --S(O).sub.2 --R.sup.9 ; R.sup.2 and R.sup.3 each independently are hydrogen, hydroxy, halo, cyano, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, hydroxyC.sub.1-6 alkyloxy, C.sub.1-6 alkyloxy-C.sub.1-6 alkyloxy, aminoC.sub.1-6 alkyloxy, mono- or di(C.sub.1-6 alkyl)aminoC.sub.1-6 alkyloxy, Ar.sup.1, Ar.sup.2 C.sub.1-6 alkyl, Ar.sup.2 oxy, Ar.sup.2 C.sub.1-6 alkyloxy, hydroxycarbonyl, C.sub.1-6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C.sub.2-6 alkenyl; or when on adjacent positions R.sup.2 and R.sup.3 taken together may form a bivalent radical; R.sup.4 and R.sup.5 each independently are hydrogen, Ar.sup.1, C.sub.1-6 alkyl, C.sub.1-6 alkyloxyC.sub.1-6 alkyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkylthio, amino, hydroxycarbonyl, C.sub.1-6 alkyloxycarbonyl, C.sub.1-6 alkylS(O)C.sub.1-6 alkyl or C.sub.1-6 alkylS(O).sub.2 --C.sub.1-6 alkyl; R.sup.6 and R.sup.7 each independently are hydrogen, halo, cyano, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy or Ar.sup.2 oxy; R.sup.8 is hydrogen, C.sub.1-6 alkyl, cyano, hydroxycarbonyl, C.sub.1-6 alkyloxycarbonyl, C.sub.1-6 alkylcarbonylC.sub.1-6 alkyl, cyanoC.sub.1-6 alkyl, C.sub.1-6 alkyloxy-carbonylC.sub.1-6 alkyl, hydroxycarbonylC.sub.1-6 alkyl, hydroxyC.sub.1-6 alkyl, aminoC.sub.1-6 alkyl, mono- or di(C.sub.1-6 alkyl)aminoC.sub.1-6 alkyl, haloC.sub.1-6 alkyl, C.sub.1-6 alkyloxy-C.sub.1-6 alkyl, aminocarbonylC.sub.1-6 alkyl, Ar.sup.1, Ar.sup.2 C.sub.1-6 alkyloxyC.sub.1-6 alkyl, C.sub.1-6 alkylthioC.sub.1-6 alkyl; R.sup.10 is hydrogen, C.sub.1-6 alkyl or halo; R.sup.11 is hydrogen or C.sub.1-6 alkyl; having farnesyl transferase inhibiting activity; their preparation, compositions containing them and their use as a medicine.

  本发明涉及式(I)的化合物，其立体异构体和药学上可接受的酸或碱盐，其中虚线代表可选键；X是氧或硫；R.sup.1是氢，C.sub.1-12烷基，Ar.sup.1，Ar.sup.2 C.sub.1-6烷基，喹啉基C.sub.1-6烷基，吡啶基C.sub.1-6烷基，羟基C.sub.1-6烷基，C.sub.1-6烷氧基C.sub.1-6烷基，单取代或双(C.sub.1-6烷基)-氨基C.sub.1-6烷基，氨基C.sub.1-6烷基，或式--Alk.sup.1 --C(.dbd.O)--R.sup.9，--Alk.sup.1 --S(O)--R.sup.9或--Alk.sup.1 --S(O).sub.2 --R.sup.9的基团；R.sup.2和R.sup.3各自独立地是氢，羟基，卤素，氰基，C.sub.1-6烷基，C.sub.1-6烷氧基，羟基C.sub.1-6烷氧基，C.sub.1-6烷氧基-C.sub.1-6烷氧基，氨基C.sub.1-6烷氧基，单取代或双(C.sub.1-6烷基)氨基C.sub.1-6烷氧基，Ar.sup.1，Ar.sup.2 C.sub.1-6烷基，Ar.sup.2氧基，Ar.sup.2 C.sub.1-6烷氧基，羟基羰基，C.sub.1-6烷氧羰基，三卤甲基，三卤甲氧基，C.sub.2-6烯基；或当R.sup.2和R.sup.3在相邻位置时，结合在一起可以形成二价基团；R.sup.4和R.sup.5各自独立地是氢，Ar.sup.1，C.sub.1-6烷基，C.sub.1-6烷氧基C.sub.1-6烷基，C.sub.1-6烷氧基，C.sub.1-6烷硫基，氨基，羟基羰基，C.sub.1-6烷氧羰基，C.sub.1-6烷硫氧基C.sub.1-6烷基或C.sub.1-6烷硫氧.sub.2 --C.sub.1-6烷基；R.sup.6和R.sup.7各自独立地是氢，卤素，氰基，C.sub.1-6烷基，C.sub.1-6烷氧基或Ar.sup.2氧基；R.sup.8是氢，C.sub.1-6烷基，氰基，羟基羰基，C.sub.1-6烷氧羰基，C.sub.1-6烷基羰基C.sub.1-6烷基，氰基C.sub.1-6烷基，C.sub.1-6烷氧-羰基C.sub.1-6烷基，羟基羰基C.sub.1-6烷基，羟基C.sub.1-6烷基，氨基C.sub.1-6烷基，单取代或双(C.sub.1-6烷基)氨基C.sub.1-6烷基，卤素C.sub.1-6烷基，C.sub.1-6烷氧基-C.sub.1-6烷基，氨基羰基C.sub.1-6烷基，Ar.sup.1，Ar.sup.2 C.sub.1-6烷氧基C.sub.1-6烷基，C.sub.1-6烷硫基C.sub.1-6烷基；R.sup.10是氢，C.sub.1-6烷基或卤素；R.sup.11是氢或C.sub.1-6烷基；具有法尼基转移酶抑制活性；它们的制备，含有它们的组合物及其作为药物的用途。
• Farnesyl transferase inhibiting 6-(substituted phenyl) Methy)-quinoline and quinazoline derinazoline derivaties
  申请人：——

  公开号：US20040048882A1

  公开（公告）日：2004-03-11

  This invention comprises the novel compounds of formula (I) wherein r, s, t, Y 1 —Y 2 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 have defined meanings, having farnesyl transferase inhibiting activity; their preparation, compositions containing them and their use as a medicine.

  这项发明包括具有法尼醇转移酶抑制活性的式(I)的新化合物，其中r、s、t、Y1—Y2、R1、R2、R3、R4、R5、R6和R7具有定义的含义；它们的制备、含有它们的组合物以及它们作为药物的用途。
• Quinolin-2-one derivatives useful as anticancer agents
  申请人：Pfizer Inc.

  公开号：US06495564B1

  公开（公告）日：2002-12-17

  The present invention relates to compounds of formula 1 and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are as defined herein. The above compounds of formula 1 are useful in the treatment of hyperproliferative disorders, such as cancer, in mammals. The invention also relates to pharmaceutical compositions containing the compounds of formula 1 and to methods of inhibiting abnormal cell growth, including cancer, in a mammal by administering the compounds of formula 1 to a mammal requiring such treatment.

  本发明涉及式1的化合物以及其药学上可接受的盐、前药和溶剂化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10和R11如本文所定义。式1的上述化合物在哺乳动物中用于治疗高增殖性疾病，如癌症。本发明还涉及含有式1的化合物的药物组合物，以及通过向需要此类治疗的哺乳动物给予式1的化合物来抑制异常细胞生长，包括癌症的方法。
• [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。