5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-3-(3-methoxyphenyl)-2,1-benzisoxazole | 190898-65-8

• 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: 5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-3-(3-methoxyphenyl)-2,1-benzisoxazole
• 英文别名: 5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-3-(3-methoxyphenyl)-2,1-benzoxazole
• CAS: 190898-65-8
• 化学式: C₂₃H₁₈ClNO₄
• 分子量: 407.853
• InChiKey: DYMSGKBJYIXWAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  53.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-3-(3-methoxyphenyl)-2,1-benzisoxazole 在 钯 氢气 作用下， 25.0 ℃ 、14.0 kPa 条件下， 反应 12.0h， 以yielding 31.2 g (100%) of (3-methoxyphenyl)[2-amino-5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]phenyl]methanone (interm. 7-c)的产率得到(3-methoxyphenyl)[2-amino-5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]phenyl]methanone
  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加合盐，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烷基或式--Alk1--C(=O)--R9，--Alk1--S(O)--R9或--Alk1--S(O)2--R9的基团；R2和R3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，羟基羧基，C1-6烷氧羰基，三卤甲基，三卤甲氧基，C2-6烯基；或当相邻的R2和R3取在一起时可以形成二价基团；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，羟基羧基，C1-6烷氧羰基，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，卤素，氰基，C1-6烷基，C1-6烷氧基或Ar2氧基；R8为氢，C1-6烷基，氰基，羟基羧基，C1-6烷氧羰基，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，羟基羧基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，卤素C1-6烷基，C1-6烷氧基-C1-6烷基，氨基羧基C1-6烷基，Ar1，Ar2C1-6烷氧基C1-6烷基，C1-6烷硫基C1-6烷基；R10为氢，C1-6烷基或卤素；R11为氢或C1-6烷基；具有法尼酰转移酶抑制活性；它们的制备，包含它们的组合物以及它们作为药物的用途。

  公开号：

  US05968952A1
• 作为产物：
  描述：

  3-甲氧基苯乙腈 、 2-(4-Chlorophenyl)-2-(4-nitrophenyl)-1,3-dioxolane 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 以30 g (90%)的产率得到5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-3-(3-methoxyphenyl)-2,1-benzisoxazole
  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

• 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。
• [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。
• Farnesyl protein transferase inhibiting (imidazol-5-yl) methyl-2-quinolinone derivatives
  申请人：Janssen Pharmaceutica N.V.

  公开号：US06420387B1

  公开（公告）日：2002-07-16

  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, hydroxyC1-6akyloxy, 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, —SR10, —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.

  该发明涉及式（I）的新化合物，其中点线表示可选键；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、单烷基或双（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（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、单烷基或双（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、氨基羧基C1-6烷基，或式—O—R10、—SR10、—N—R11R12的基团；R17为氢、卤素、氰基、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。
• 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：——