(+/-)-6-[2-(4-chlorophenyl)-2-oxiranyl]-1-methyl-4-phenyl-2(1H)-quinolinone | 190898-57-8

• 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-[2-(4-chlorophenyl)-2-oxiranyl]-1-methyl-4-phenyl-2(1H)-quinolinone
• 英文别名: 6-[2-(4-Chlorophenyl)oxiran-2-yl]-1-methyl-4-phenylquinolin-2-one
• CAS: 190898-57-8
• 化学式: C₂₄H₁₈ClNO₂
• 分子量: 387.865
• InChiKey: UILVGUDFRUDVRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  咪唑 、 (+/-)-6-[2-(4-chlorophenyl)-2-oxiranyl]-1-methyl-4-phenyl-2(1H)-quinolinone 以 2-氨基-3-氯-1,4-萘醌 为溶剂， 以2 g (37%)的产率得到(+/-)-6-[1-(4-chlorophenyl)-2-hydroxy-1-(1H-imidazol-1-yl)ethyl]-1-methyl-4-phenyl-2(1H)-quinolinone monohydrate
  参考文献：
  名称：

  Farnesyl transferase inhibiting 2-quinolone derivatives

  摘要：

  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。

  公开号：

  US05968952A1
• 作为产物：
  描述：

  6-(4-chlorobenzoyl)-1-methyl-4-phenyl-2(1H)-quinolinone 、 三甲基碘化亚砜 在 二甲基亚砜 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 以17.6 g (100%)的产率得到(+/-)-6-[2-(4-chlorophenyl)-2-oxiranyl]-1-methyl-4-phenyl-2(1H)-quinolinone
  参考文献：
  名称：

  Farnesyl transferase inhibiting 2-quinolone derivatives

  摘要：

  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。

  公开号：

  US05968952A1

文献信息

• 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
• US5968952A
  申请人：——

  公开号：US5968952A

  公开（公告）日：1999-10-19
• [EN] FARNESYL TRANSFERASE INHIBITING 2-QUINOLONE DERIVATIVES<br/>[FR] DERIVES DE 2-QUINOLONE INHIBANT LA FARNESYLE TRANSFERASE
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1997016443A1

  公开（公告）日：1997-05-09

  (EN) 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, Ar2C1-6alkyloxy, 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, C1-6alkyloxycarbonyl, 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, C1-6alkylcarbonylC1-6alkyl, cyanoC1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, hydroxycarbonyl-C1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, haloC1-6alkyl, C1-6alkyloxy-C1-6alkyl, aminocarbonylC1-6alkyl, Ar1, Ar2C1-6alkyloxyC1-6alkyl, 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.(FR) La présente invention concerne des composés de la formule (I), des formes stéréo-isomères de ceux-ci, ainsi que des sels d'addition de base ou d'acide de ceux-ci, acceptables sur le plan pharmacologique. Dans cette formule, les lignes en pointillé représentent une liaison facultative, X représente oxygène ou soufre, R1 représente hydrogène, alkyle C1-12, Ar1, Ar2alkyle C1-6, quinolinyl-alkyle C1-6, pyridyl-alkyle C1-6, hydroxy-alkyle C1-6, alkyloxy C1-6-alkyle C1-6, mono ou di(alkyle C1-6)-amino-alkyle C1-6, amino-alkyle C1-6, ou un radical de la formule -Alk1-C(=O)-R9, -Alk1-S(O)-R9, ou -Alk1-S(O)2-R9, R2 et R3 représentent chacun indépendamment hydrogène, hydroxy, halo, cyano, alkyle C1-6, alkyloxy C1-6, hydroxy-alkyloxy C1-6, alkyloxy C1-6-alkyloxy C1-6, amino-alkyloxy C1-6, mono ou di(alkyle C1-6)amino-alkyloxy C1-6, Ar1, Ar2alkyle C1-6, Ar2oxy, Ar2alkyloxy C1-6, hydroxycarbonyle, alkyloxycarbonyle C1-6, trihalométhyle, trihalométhoxy, alcényle C2-6, ou bien lorsque R2 et R3 sont dans des positions adjacentes, pris ensemble, ils peuvent former un radical bivalent, R4 et R5 représentent chacun indépendamment hydrogène, Ar1, alkyle C1-6, alkyloxyC1-6-alkyle C1-6, alkyloxy C1-6, alkylthio C1-6, amino, hydroxycarbonyle, alkyloxy C1-6-carbonyle, alkyle C1-6S(O)alkyle C1-6 ou alkyle C1-6S(O)2-alkyle C1-6, R6 et R7 représentent chacun indépendamment hydrogène, halo, cyano, alkyle C1-6, alkyloxy C1-6 ou Ar2oxy, R8 représente hydrogène, alkyle C1-6, cyano, hydroxycarbonyle, alkyloxycarbonyle C1-6, alkyle C1-6-carbonyl-alkyle C1-6,cyano-alkyle C1-6, alkyloxy C1-6-carbonyl-alkyle C1-6, hydroxycarbonyl-alkyle C1-6, hydroxy-alkyle C1-6, amino-alkyle C1-6, mono ou di(alkyle C1-6)amino-alkyle C1-6, halo-alkyle C1-6, alkyloxy C1-6-alkyle C1-6, aminocarbonyle-alkyle C1-6, Ar1, Ar2alkyloxy C1-6-alkyle C1-6, alkylthio C1-6-alkyle C1-6, R10 représente hydrogène, alkyle C1-6 ou halo, R11 représente hydrogène ou alkyle C1-6. Ces composés possèdent une activité inhibitrice de la farnésyle transférase. On décrit également la préparation de ces composés, des compositions les contenant ainsi que leur utilisation en tant que médicament.
• 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。