公开(公告)号：US06169096A

公开(公告)日：2001-01-02

申请号：US09363353

申请日：1999-07-29

申请人： Marc Gaston Venet ,  Patrick Ren{acute over (e)} Angibaud ,  Philippe Muller ,  G{acute over (e)}rard Charles Sanz

发明人： Marc Gaston Venet ,  Patrick Ren{acute over (e)} Angibaud ,  Philippe Muller ,  G{acute over (e)}rard Charles Sanz

IPC分类号： A01N4342

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D407/14 ,  C07D413/14 ,  Y02P20/55

摘要： 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.

摘要翻译： 本发明包括式（I）的新化合物，其中虚线表示任选的键; X是氧或硫; R1是氢，C1-12烷基，Ar1，Ar2C1-6烷基，喹啉基C 1-6烷基，吡啶基C 1-6烷基，羟基C 1-6烷基，C 1-6烷氧基C 1-6烷基，一或二（C 1-6烷基）氨基C 1-6烷基，氨基C 1-6烷基或 式-Alk1-C（= O）-R9，-Alk1-S（O）-R9或-Alk1-S（O）2-R9的基团; R 2，R 3和R 16各自独立地为氢，羟基，卤素，氰基，C 1-6烷基，C 1-6烷氧基，羟基C 1-6烷氧基，C 1-6烷氧基C 1-6烷氧基，氨基C 1-6烷氧基，单 - 或二（C 1-6烷基）氨基C 1-6烷氧基 Ar 1，Ar 2 C 1-6烷基，Ar 2氧基，Ar 2 C 1-6烷氧基，羟基羰基，C 1-6烷氧基羰基，三卤代甲基，三卤代甲氧基，C 2-6烯基; R 4和R 5各自独立地为氢，卤素，Ar 1，C 1-6烷基，羟基C 1-6烷基，C 1-6烷氧基C 1-6烷基，C 1-6烷氧基，C 1-6烷硫基，氨基，羟基羰基，C 1-6烷氧基羰基，C 1-6烷基S（O） C 1-6烷基或C 1-6烷基S（O）2 C 1-6烷基; R 6和R 7各自独立地为氢，卤素，氰基，C 1-6烷基，4,4-二甲基 - 恶唑基，C 1-6烷氧基或Ar 2氧基; R 8是氢，C 1-6烷基，氰基，羟基羰基，C 1-6烷氧基羰基，C 1-6烷基羰基C 1-6

公开(公告)号：US06177432B1

公开(公告)日：2001-01-23

申请号：US09403705

申请日：1999-10-22

申请人： Patrick Ren{acute over (e)} Angibaud ,  Marc Gaston Venet ,  Eddy Jean Edgard Freyne

发明人： Patrick Ren{acute over (e)} Angibaud ,  Marc Gaston Venet ,  Eddy Jean Edgard Freyne

IPC分类号： A61K31505

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D239/82 ,  C07D249/08 ,  C07D403/06 ,  C07D405/04

摘要： 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.

摘要翻译： 本发明涉及配制药学上可接受的酸加成盐和其立体化学异构形式的化合物，其中虚线表示任选的键; X是氧或硫; R 1和R 2各自独立地为氢，羟基，卤素，氰基，C 1-6烷基，三卤代甲基，三卤甲氧基，C 2-6烯基，C 1-6烷氧基，羟基C 1-6烷氧基，C 1-6烷氧基C 1-6烷氧基，C 1-6烷氧基羰基，氨基C 1-6烷氧基， 或二（C 1-6烷基）氨基C 1-6烷氧基，Ar 1，Ar 1 C 1-6烷基，Ar 1氧基，Ar 1 C 1-6烷氧基; 或者当在相邻位置R1和R2一起可以形成二价基团时; R 3和R 4各自独立地为氢，卤素，氰基，C 1-6烷基，C 1-6烷氧基，Ar 1氧基，C 1-6烷硫基，二（C 1-6烷基）氨基，三卤甲基，三卤甲氧基; R5是氢，卤素，氰基，任意取代的C 1-6烷基，C 1-6烷氧基羰基或Ar 1; 或式-OR 10，-SR 10，-NR 11 R 12的基团; R6是任选取代的咪唑基部分; R 7是氢或C 1-6烷基，条件是虚线不代表键; R8是氢，C1-6烷基或Ar2CH2或Het1CH2; R9是氢，C1-6烷基，C1-6烷氧基或卤素，或R8和R9一起可以形成二价基; Ar1和Ar2是任选取代的苯基，Het1是任选取代的吡啶基; 具有法呢基转移酶抑制活性; 其制剂，含有它们的组合物及其作为药物的用途。