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    • 22. 发明授权
    • Intermediate compounds in the preparation of farnnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with N-or C linked imidazoles
    • 中间体化合物制备法尼烯基转移酶抑制被N-或C连接的咪唑取代的1,8-环化喹啉酮衍生物
    • US06444812B1
    • 2002-09-03
    • US09725391
    • 2000-11-29
    • Marc Gaston VenetPatrick René AngibaudYannick Aimé Eddy LignyVirginie Sophie PonceletGerard Charles Sanz
    • Marc Gaston VenetPatrick René AngibaudYannick Aimé Eddy LignyVirginie Sophie PonceletGerard Charles Sanz
    • C07D26538
    • C07D471/06C07D455/04
    • This invention concerns intermediates in the preparation of 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; —A— is a bivalent radical of formula; 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, Ar, Ar—C1-6alkyl, Ar-oxy, Ar—C1-6alkyloxy; 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, Ar-oxy, C1-6alkylthio, di(C1-6alkyl)amino, trihalomethyl, trihalomethoxy, or when on adjacent positions R3 and R4 taken together may form a bivalent radical; R5 is an imidazolyl substituted with hydrogen or C1-6alkyl; R6 hydrogen, hydroxy, halo, cyano, optionally substituted C1-6alkyl, C1-6alkyloxycarbonyl or Ar; or a radical of formula —O—R7, —S—R8, —N—R8R9; and Ar is optionally substituted phenyl; and of the preparation, thereof.
    • 本发明涉及制备药学上可接受的酸加成盐及其立体化学异构形式的化合物的中间体,其中虚线表示任选的键; X是氧或硫; -A-是式的二价基团; 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,Ar-C 1-6烷基,Ar-氧基,Ar-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-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, 可形成二价基团; R5是被氢或C1-6烷基取代的咪唑基; R6,氢,羟基,卤素,氰基,任选取代的C 1-6烷基,C 1-6烷氧基羰基或Ar; 或式-O-R7,-S-R8,-N-R8R9的基团; 和Ar是任选取代的苯基; 及其制备方法。
    • 28. 发明授权
    • Pyrido-and pyrimidopyrimidine derivatives as anti-profilerative agents
    • 吡啶并嘧啶并嘧啶衍生物作为抗衰老剂
    • US07799772B2
    • 2010-09-21
    • US10596512
    • 2004-12-15
    • Eddy Jean Edgard FreynePierre Henri StorckVirginie Sophie PonceletTimothy Pietro Suren Perera
    • Eddy Jean Edgard FreynePierre Henri StorckVirginie Sophie PonceletTimothy Pietro Suren Perera
    • A01N43/00A61K31/33C07D225/00C07D295/00
    • C07D498/16C07D471/04C07D487/04C07D487/16C07D487/22
    • The present invention concerns the compounds of formula wherein a1-a2=a3-a4 represents a divalent radical selected from N—CH═CH—CH, N—CH═N—CH or CH—CH═N—CH; Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR13—C1-5alkyl-, —C1-6alkyl-NH—CO— or —CO—NH—C1-6alkyl-; X1 represents —O— or —NR11—; X2 represents —C1-2alkyl-, —O—C1-2alkyl, —O— or —O—CH2—; R1 represents hydrogen or halo; R2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C1-4alkyloxycarbonyl-, Het16-carbonyl- or Ar5; R3 represents hydrogen; R4 represents hydroxy, C1-4alkyloxy-, Ar4—C1-4alkyloxy or R4 represents C1-4alkyloxy substituted with one or where possible two or more substituents selected from C1-4alkyloxy- or Het2-; R11 represents hydrogen; R12 represents hydrogen, C1-4alkyl- or C1-4alkyl-oxy-carbonyl-; R13 represents Het14-C1-4alkyl, in particular morpholinyl-C1-4alkyl; Het2 represents a heterocycle selected from morpholinyl or piperidinyl optionally substituted with C1-4alkyl-, preferably methyl; Het14 represents morpholinyl; Het16 represents a heterocycle selected from morpholinyl or pyrrolidinyl; Ar4 represents phenyl; Ar5 represents phenyl optionally substituted with cyano.
    • 本发明涉及下式的化合物:其中a 1-a 2 = a 3-a 4表示选自N-CH = CH,N-CH = N-CH或CH-CH = N-CH的二价基团; Z表示NH; Y表示-C3-9烷基 - ,-C1-5烷基-NR13-C1-5烷基 - ,C1-6烷基-NH-CO-或-CO-NH-C1-6烷基 - ; X1表示-O-或-NR11-; X2表示-C1-2烷基 - , - O-C1-2烷基,-O-或-O-CH2-; R1表示氢或卤素; R 2表示氢,氰基,卤素,羟基羰基 - ,C 1-4烷氧基羰基 - ,Het 16 - 羰基 - 或Ar 5; R3表示氢; R 4表示羟基,C 1-4烷氧基 - ,Ar 4 -C 1-4烷氧基或R 4表示被一个或多个可能的两个或多个选自C 1-4烷氧基或Het 2-的取代基取代的C 1-4烷氧基; R11表示氢; R 12表示氢,C 1-4烷基 - 或C 1-4烷基 - 氧基 - 羰基 - ; R13表示Het14-C1-4烷基,特别是吗啉基-C 1-4烷基; Het2表示选自任选被C 1-4烷基,优选甲基取代的吗啉基或哌啶基的杂环; Het14代表吗啉基; Het16表示选自吗啉基或吡咯烷基的杂环; Ar4表示苯基; Ar 5表示任选被氰基取代的苯基。