3-(3-chlorophenyl)-5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-2,1-benzisoxazole | 190898-77-2

• 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: 3-(3-chlorophenyl)-5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-2,1-benzisoxazole
• 英文别名: 3-(3-chlorophenyl)-5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-2,1-benzoxazole
• CAS: 190898-77-2
• 化学式: C₂₂H₁₅Cl₂NO₃
• 分子量: 412.272
• InChiKey: LKBPYEMOOOFALD-UHFFFAOYSA-N

物化性质

• 熔点：
  120 °C
• 沸点：
  577.6±50.0 °C(Predicted)
• 密度：
  1.388±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  44.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3-chlorophenyl)-5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-2,1-benzisoxazole 在 盐酸 、 正丁基锂 、 titanium(III) chloride 、 三乙基氯硅烷 、 水 作用下， 以 四氢呋喃 为溶剂， 生成 (+/-)-[2-amino-5-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]phenyl](3-chlorophenyl)methanone
  参考文献：
  名称：

  5-Imidazolyl-quinolinones, -quinazolinones and -benzo-azepinones as farnesyltransferase inhibitors

  摘要：

  The evaluation of structure activity relationships associated with the modification of the R115777 quinolinone ring moiety displaying potent in vitro inhibiting activity is described. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00180-x
• 作为产物：
  描述：

  4-氯-4-硝基苯甲酮 在 sodium hydroxide 、 对甲苯磺酸 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 25.0h， 生成 3-(3-chlorophenyl)-5-[2-(4-chlorophenyl)-1,3-dioxolan-2-yl]-2,1-benzisoxazole
  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

• Farnesyltransferase inhibiting quinazolinones
  申请人：Janssen-Cilag S.A.

  公开号：US06177432B1

  公开（公告）日：2001-01-23

  This invention concerns compounds of formula the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein the dotted line represents an optional bond; X is oxygen or sulfur; R1 and R2 each independently are hydrogen, hydroxy, halo, cyano, C1-6alkyl, trihalomethyl, trihalomethoxy, C2-6alkenyl, C1-6alkyloxy, hydroxyC1-6alkyloxy, C1-6alkyloxyC1-6alkyloxy, C1-6alkyloxycarbonyl, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, Ar1, Ar1C1-6alkyl, Ar1oxy, Ar1C1-6alkyloxy; or when on adjacent positions R1 and R2 taken together may form a bivalent radical; R3 and R4 each independently are hydrogen, halo, cyano, C1-6alkyl, C1-6alkyloxy, Ar1oxy, C1-6alkylthio, di(C1-6alkyl)amino, trihalomethyl, trihalomethoxy; R5 is hydrogen, halo, cyano, optionally substituted C1-6alkyl, C1-6alkyloxycarbonyl or Ar1; or a radical of formula —OR10, —SR10, —NR11R12; R6 is an optionally substituted imidazolyl moiety; R7 is hydrogen or C1-6alkyl provided that the dotted line does not represent a bond; R8 is hydrogen, C1-6alkyl or Ar2CH2 or Het1CH2; R9 is hydrogen, C1-6alkyl, C1-6alkyloxy or halo, or R8 and R9 taken together may form a bivalent radical; Ar1 and Ar2 are optionally substituted phenyl and Het1 is optionally substituted pyridinyl; having farnesyl transferase inhibiting activity; their preparation, compositions containing them and their use as a medicine.

  这项发明涉及公式化合物的药用可接受酸盐和其立体化学异构体形式，其中虚线代表可选键；X为氧或硫；R1和R2各自独立地为氢、羟基、卤、氰基、C1-6烷基、三卤甲基、三卤甲氧基、C2-6烯基、C1-6烷氧基、羟基C1-6烷氧基、C1-6烷氧基C1-6烷氧基、C1-6烷氧羰基、氨基C1-6烷氧基、单或双(C1-6烷基)氨基C1-6烷氧基、Ar1、Ar1C1-6烷基、Ar1氧基、Ar1C1-6烷氧基；或当R1和R2在相邻位置时，两者结合形成二价基团；R3和R4各自独立地为氢、卤、氰基、C1-6烷基、C1-6烷氧基、Ar1氧基、C1-6烷硫基、双(C1-6烷基)氨基、三卤甲基、三卤甲氧基；R5为氢、卤、氰基、可选择取代的C1-6烷基、C1-6烷氧羰基或Ar1；或公式—OR10、—SR10、—NR11R12的基团；R6为可选择取代的咪唑基团；R7为氢或C1-6烷基，但虚线不代表键；R8为氢、C1-6烷基或Ar2CH2或Het1CH2；R9为氢、C1-6烷基、C1-6烷氧基或卤基，或R8和R9结合形成二价基团；Ar1和Ar2为可选择取代的苯基，Het1为可选择取代的吡啶基；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。
• (Imidazol-5-yl)methyl-2-quinolinone derivatives as inhibitors of smooth muscle cell proliferation
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US06365600B1

  公开（公告）日：2002-04-02

  This invention comprises the use of 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, quinolinylC1-6alkyul, pyridylC1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, aminoC1-6alkyl, or a radical of formula —Alk1—C(=))—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, Ar1Ar2C1-6alkyl, Ar2-oxy, Ar2C1-6alkyloxy, hydroxycarbonyl, C1-6alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C2-6alkenyl; R4 and R5 each independently are hydrogen, halo, Ar1, C1-6-alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkyloxy, C1-6alkylthio, amino, hydroxycarbony, C1-6alkyloxycarbonyl, C1-6alkylS(O)C1-6alkul or C1-6alkylS(O)2C1-6alkyl; R6 and R7 independenly are hydrogen, halo, cyano, C1-6alkyl, 4,4-dimethyl-oxazolyl, C1-6alkyloxy or Ar2oxyl 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, C106alkyloxycarbonyl, Ar1; R18 is hydrogen, C1-6alkyl, C1-6alkyloxy or halo; R19 is hydrogen or C1-6alkyl; for the manufacture of a medicament to inhibit smooth muscle cell proliferation.

  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。
• Method of use of (imidazol-5-yl)methyl-2-quinolinone derivatives to inhibit smooth muscle cell proliferation
  申请人：——

  公开号：US20040198771A1

  公开（公告）日：2004-10-07

  This invention comprises the use of compounds of formula (I) 1 wherein the dotted line represents an optional bond; X is oxygen or sulfur; R 1 is hydrogen, C 1-12 alkyl, Ar 1 , Ar 2 C 1-6 alkyl, quinolinylC 1-6 alkyl, pyridylC 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, aminoC 1-6 alkyl, or a radical of formula —Alk 1 —C(═O)—R 9 , —Alk 1 —S(O)—R 9 or —Alk 1 —S(O) 2 —R 9 ; R 2 , R 3 and R 16 each independently are hydrogen, hydroxy, halo, cyano, C 1-6 alkyl, C 1-6 alkyloxy, hydroxyC 1-6 alkyloxy, C 1-6 alkyloxyC 1-6 alkyloxy, aminoC 1-6 alkyloxy, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyloxy, Ar 1 , Ar 2 C 1-6 alkyl, Ar 2 oxy, Ar 2 C 1-6 alkyloxy, hydroxycarbonyl, C 1-6 alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C 2-6 alkenyl; R 4 and R 5 each independently are hydrogen, halo, Ar 1 , C 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, C 1-6 alkyloxy, C 1-6 alkylthio, amino, hydroxycarbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylS(O)C 1-6 alkyl or C 1-6 alkylS(O) 2 C 1-6 alkyl; R 6 and R 7 each independently are hydrogen, halo, cyano, C 1-6 alkyl, 4,4-dimethyl-oxazolyl, C 1-6 alkyloxy or Ar 2 oxy; R 8 is hydrogen, C 1-6 alkyl, cyano, hydroxycarbonyl, C 1-6 alkyloxycarbonyl, C 1-6 alkylcarbonylC 1-6 alkyl, cyanoC 1-6 alkyl, C 1-6 alkyloxycarbonylC 1-6 alkyl, carboxyC 1-6 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, imidazolyl, haloC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, aminocarbonylC 1-6 alkyl, or a radical of formula —O—R 10 , —S—R 10 , —N—R 11 R 12 ; R 17 is hydrogen, halo, cyano, C 1-6 alkyl, C 1-6 alkyloxycarbonyl, Ar 1 ; R 18 is hydrogen, C 1-6 alkyl, C 1-6 alkyloxy or halo; R 19 is hydrogen or C 1-6 alkyl; for the manufacture of a medicament to inhibit smooth muscle cell proliferation.

  本发明涉及化合物的使用，其化学式为（I）1，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、单或双（C1-6烷基）氨基C1-6烷基、氨基C1-6烷基，或式为—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、氰、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、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、氰、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、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、单或双（C1-6烷基）氨基C1-6烷基、咪唑基、卤基C1-6烷基、C1-6烷氧基C1-6烷基、氨基羧基C1-6烷基，或式为—O—R10、—S—R10、—N—R11R12的基团；R17为氢、卤、氰、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；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。
• 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 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。