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    Quinazoline derivatives as VEGF inhibitors
    1.
    发明授权
    Quinazoline derivatives as VEGF inhibitors 有权
    喹唑啉衍生物作为VEGF抑制剂

    公开(公告)号：US07173038B1

    公开(公告)日：2007-02-06

    申请号：US10129336

    申请日：2000-11-01

    申请人： Andrew Peter Thomas ,  Elaine Sophie Elizabeth Stokes ,  Laurent Francois Andre Hennequin

    发明人： Andrew Peter Thomas ,  Elaine Sophie Elizabeth Stokes ,  Laurent Francois Andre Hennequin

    IPC分类号： A61K31/53 ,  A61K31/517 ,  A61K31/519 ,  C07D239/72

    CPC分类号： C07D401/12

    摘要： The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; R1 represents halogeno or C1-3alkyl; X1 represents —O—; R2 is selected from one of the following three groups: 1) C1-5alkylR3 (wherein R3 is piperidin-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C1-4hydroxyalkyl and C1-4alkoxy; 2) C2-5alkenylR3 (wherein R3 is as defined hereinbefore); 3) C2-5alkynylR3 (wherein R3 is as defined hereinbefore); and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof, processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as a active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of number of disease states including cancer and rheumatoid arthritis.

    摘要翻译： 本发明涉及式（I）的喹唑啉衍生物，其中m为1至3的整数; R 1表示卤代或C 1-3烷基; X 1表示-O-; R 2选自以下三个基团之一：1）C 1-5烷基R 3（其中R 3，R 3，R 3， SUP>是可以具有一个或两个选自羟基，卤代，C 1-4 - 羟基烷基和C 1-4 - 烷氧基的取代基的哌啶-4-基; 2）C （其中R 3如上文所定义）;或其中R 3和R 3如上定义。 3）C 2-5炔基R 3（其中R 3如上定义）; 并且其中任何烷基，烯基或炔基可以具有一个或多个选自羟基，卤代和氨基的取代基; 及其盐，其制备方法，含有式（I）化合物或其药学上可接受的盐作为活性成分的药物组合物。 式（I）化合物及其药学上可接受的盐抑制VEGF的作用，其在治疗包括癌症和类风湿性关节炎在内的疾病状态的数量方面具有价值。

    Quinazoline derivatives as VEGF inhibitors
    2.
    发明授权
    Quinazoline derivatives as VEGF inhibitors 有权
    喹唑啉衍生物作为VEGF抑制剂

    公开(公告)号：US08642608B2

    公开(公告)日：2014-02-04

    申请号：US12761105

    申请日：2010-04-15

    申请人： Andrew Peter Thomas ,  Elaine Sophie Elizabeth Stokes ,  Laurent Francois Andre Hennequin

    发明人： Andrew Peter Thomas ,  Elaine Sophie Elizabeth Stokes ,  Laurent Francois Andre Hennequin

    IPC分类号： A01N43/54 ,  A61K31/517 ,  C07D239/72 ,  C07D401/00

    CPC分类号： C07D401/12

    摘要： The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; R1 represents halogeno or C1-3alkyl; X1 represents —O—; R2 is selected from one of the following three groups: 1) C1-5alkylR3 (wherein R3 is piperidinyl-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy; 2) C2-5alkenylR3 (wherein R3 is as defined hereinbefore); 3) C2-5alkynylR3 (wherein R3 is as defined hereinbefore); and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

    摘要翻译： 本发明涉及式（I）的喹唑啉衍生物，其中m为1至3的整数; R1代表卤代或C1-3烷基; X1表示-O-; R2选自以下三个基团之一：1）C 1-5烷基R 3（其中R 3是可以带有一个或两个选自羟基，卤代C 1-4烷基，C 1-4羟烷基和C 1-4烷氧基的取代基的哌啶-4-基; 2）C 2-5烯基R 3（其中R 3如上所定义）; 3）C 2-5炔基R 3（其中R 3如上文所定义）; 并且其中任何烷基，烯基或炔基可以具有一个或多个选自羟基，卤代和氨基的取代基; 及其盐; 其制备方法，含有式（I）化合物或其药学上可接受的盐作为活性成分的药物组合物。 式（I）化合物及其药学上可接受的盐抑制VEGF的作用，其在治疗许多疾病状态（包括癌症和类风湿性关节炎）中是有价值的。

    Quinazoline derivatives and pharmaceutical compositions containing them
    3.
    发明授权
    Quinazoline derivatives and pharmaceutical compositions containing them 有权
    喹唑啉衍生物和含有它们的药物组合物

    公开(公告)号：US06414148B1

    公开(公告)日：2002-07-02

    申请号：US09269595

    申请日：1999-03-25

    申请人： Andrew Peter Thomas ,  Craig Johnstone ,  Edward Clayton ,  Elaine Sophie Elizabeth Stokes ,  Jean-Jacques Marcel Lohmann ,  Laurent Francois Andre Hennequin

    发明人： Andrew Peter Thomas ,  Craig Johnstone ,  Edward Clayton ,  Elaine Sophie Elizabeth Stokes ,  Jean-Jacques Marcel Lohmann ,  Laurent Francois Andre Hennequin

    IPC分类号： C07D23972

    CPC分类号： C07D401/12 ,  A61F13/02 ,  A61F13/023 ,  A61F2013/00221 ,  A61F2013/8408 ,  A61K31/517 ,  A61K31/541 ,  C07D239/94 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12

    摘要： The invention relates to quinazoline derivatives of formula (1) wherein m is an integer from 1 to 2; R1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C1-3alkyl, C1-3alkoxy, C1-3alkylthio, or —NR5R6 (wherein R5 and R6, which may be the same or different, each represents hydrogen or C1-3alkyl); R2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R3 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X1 represents —O—, —CH2—, —S—, —SO—, —SO2—, —NR7CO—, —CONR8—, —SO2NR9—, —NR10SO2— or —NR11— (wherein R7, R8, R9, R10 and R11 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl); R4 represents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted group selected from alkyl and a 5 or 6 membered saturated carbocyclic or heterocyclic group, and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

    摘要翻译： 本发明涉及式（1）的喹唑啉衍生物，其中m为1至2的整数; R 1表示氢，羟基，卤代，硝基，三氟甲基，氰基，C 1-3烷基，C 1-3烷氧基，C 1-3烷硫基或-NR 5 R 6（其中R 5和R 6可以相同或不同，各自表示氢或C 1-3烷基 ）; R2代表氢，羟基，卤代，甲氧基，氨基或硝基; R3表示羟基，卤代，C1-3烷基，C1-3烷氧基，C1-3烷酰氧基，三氟甲基，氰基，氨基或硝基; X 1表示-O - ， - CH 2 - ， - S - ， - SO - ， - SO 2 - ， - NR 7 CO-，-CONR 8 - ， - SO 2 NR 9 - ， - NR 10 SO 2 - 或-NR 11 - （其中R 7，R 8，R 9，R 10 和R 11各自独立地表示氢，C 1-3烷基或C 1-3烷氧基C 2-3 - 烷基）; R 4表示任选取代的5或6元饱和碳环或杂环基团或为烯基，炔基或任选取代的烷基的基团，该烷基可含有杂原子连接基团，该烯基，炔基或烷基可带有末端任选取代的 选自烷基和5或6元饱和碳环或杂环基团的基团，及其盐; 其制备方法，含有式（I）化合物或其药学上可接受的盐作为活性成分的药物组合物。 式（I）化合物及其药学上可接受的盐抑制VEGF在治疗许多疾病状态（包括癌症和类风湿性关节炎）中具有价值的性质。

    QUINAZOLINE DERIVATIVES AS VEGF INHIBITORS
    4.
    发明申请
    QUINAZOLINE DERIVATIVES AS VEGF INHIBITORS 有权
    喹诺酮衍生物作为VEGF抑制剂

    公开(公告)号：US20110065736A1

    公开(公告)日：2011-03-17

    申请号：US12761105

    申请日：2010-04-15

    申请人： Andrew Peter Thomas ,  Elaine Sophie Elizabeth Stokes ,  Laurent Francois Andre Hennequin

    发明人： Andrew Peter Thomas ,  Elaine Sophie Elizabeth Stokes ,  Laurent Francois Andre Hennequin

    IPC分类号： A61K31/517 ,  A61P35/00 ,  A61P3/10 ,  A61P17/06 ,  A61P19/02 ,  A61P29/00 ,  A61P37/00 ,  A61P15/00 ,  A61P27/02

    CPC分类号： C07D401/12

    摘要： The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; R1 represents halogeno or C1-3alkyl; X1 represents —O—; R2 is selected from one of the following three groups: 1) C1-5alkylR3 (wherein R3 is piperidinyl-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy; 2) C2-5alkenylR3 (wherein R3 is as defined hereinbefore); 3) C2-5alkynylR3 (wherein R3 is as defined hereinbefore); and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

    摘要翻译： 本发明涉及式（I）的喹唑啉衍生物，其中m为1至3的整数; R1代表卤代或C1-3烷基; X1表示-O-; R2选自以下三个基团之一：1）C 1-5烷基R 3（其中R 3是可以带有一个或两个选自羟基，卤代C 1-4烷基，C 1-4羟烷基和C 1-4烷氧基的取代基的哌啶-4-基; 2）C 2-5烯基R 3（其中R 3如上所定义）; 3）C 2-5炔基R 3（其中R 3如上文所定义）; 并且其中任何烷基，烯基或炔基可以具有一个或多个选自羟基，卤代和氨基的取代基; 及其盐; 其制备方法，含有式（I）化合物或其药学上可接受的盐作为活性成分的药物组合物。 式（I）化合物及其药学上可接受的盐抑制VEGF的作用，其在治疗许多疾病状态（包括癌症和类风湿性关节炎）中是有价值的。

    Quinazoline derivatives and pharmaceutical compositions containing them
    5.
    再颁专利
    Quinazoline derivatives and pharmaceutical compositions containing them 失效
    喹唑啉衍生物和含有它们的药物组合物

    公开(公告)号：USRE42353E1

    公开(公告)日：2011-05-10

    申请号：US12170027

    申请日：1997-09-23

    申请人： Andrew Peter Thomas ,  Craig Johnstone ,  Edward Clayton ,  Elaine Sophie Elizabeth Stokes ,  Jean-Jacques Marcel Lohmann ,  Laurent Francois Andre Hennequin

    发明人： Andrew Peter Thomas ,  Craig Johnstone ,  Edward Clayton ,  Elaine Sophie Elizabeth Stokes ,  Jean-Jacques Marcel Lohmann ,  Laurent Francois Andre Hennequin

    IPC分类号： C07D239/72 ,  C07D401/00 ,  C07D403/00 ,  C07D413/00 ,  C07D417/00 ,  C07D419/00

    CPC分类号： C07D401/12 ,  A61F13/02 ,  A61F13/023 ,  A61F2013/00221 ,  A61F2013/8408 ,  A61K31/517 ,  A61K31/541 ,  C07D239/94 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12

    摘要： The invention relates to quinazoline derivatives of formula (1) wherein m is an integer from 1 to 2; R1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C1-3alkyl, C1-3alkoxy, C1-3alkylthio, or —NR5R6 (wherein R5 and R6, which may be the same or different, each represents hydrogen or C1-3alkyl); R2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R3 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X1 represents —O—, —CH2—, —S—, —SO—, —SO2—, —NR7CO—, —CONR8—, —SO2NR9—, —NR10SO2— or —NR11— (wherein R7, R8, R9, R10 and R11 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl); R4 represents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted group selected from alkyl and a 5 or 6 membered saturated carbocyclic or heterocyclic group, and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

    摘要翻译： 本发明涉及式（1）的喹唑啉衍生物，其中m为1至2的整数; R 1表示氢，羟基，卤代，硝基，三氟甲基，氰基，C 1-3烷基，C 1-3烷氧基，C 1-3烷硫基或-NR 5 R 6（其中R 5和R 6可以相同或不同，各自表示氢或C 1-3烷基 ）; R2代表氢，羟基，卤代，甲氧基，氨基或硝基; R3表示羟基，卤代，C1-3烷基，C1-3烷氧基，C1-3烷酰氧基，三氟甲基，氰基，氨基或硝基; X 1表示-O - ， - CH 2 - ， - S - ， - SO - ， - SO 2 - ， - NR 7 CO-，-CONR 8 - ， - SO 2 NR 9 - ， - NR 10 SO 2 - 或-NR 11 - （其中R 7，R 8，R 9，R 10 和R 11各自独立地表示氢，C 1-3烷基或C 1-3烷氧基C 2-3 - 烷基）; R 4表示任选取代的5或6元饱和碳环或杂环基团或为烯基，炔基或任选取代的烷基的基团，该烷基可含有杂原子连接基团，该烯基，炔基或烷基可带有末端任选取代的 选自烷基和5或6元饱和碳环或杂环基团的基团，及其盐; 其制备方法，含有式（I）化合物或其药学上可接受的盐作为活性成分的药物组合物。 式（I）化合物及其药学上可接受的盐抑制VEGF在治疗许多疾病状态（包括癌症和类风湿性关节炎）中具有价值的性质。

    Quinazoline derivatives and pharmaceutical compositions containing them
    7.
    发明授权
    Quinazoline derivatives and pharmaceutical compositions containing them 有权
    喹唑啉衍生物和含有它们的药物组合物

    公开(公告)号：US06673803B2

    公开(公告)日：2004-01-06

    申请号：US10080716

    申请日：2002-02-25

    申请人： Andrew Peter Thomas ,  Craig Johnstone ,  Elaine Sophie Elizabeth Stokes ,  Jean-Jacques Marcel Lohmann ,  Laurent Francois Andre Hennequin

    发明人： Andrew Peter Thomas ,  Craig Johnstone ,  Elaine Sophie Elizabeth Stokes ,  Jean-Jacques Marcel Lohmann ,  Laurent Francois Andre Hennequin

    IPC分类号： A61K31517

    CPC分类号： C07D401/12 ,  A61F13/02 ,  A61F13/023 ,  A61F2013/00221 ,  A61F2013/8408 ,  A61K31/517 ,  A61K31/541 ,  C07D239/94 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12

    摘要： The invention relates to quinazoline derivatives of formula (I) wherein m is an integer from 1 to 2; R1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C1-3alkyl, C1-3alkoxy, C1-3alkylthio, or —NR5R6 (wherein R5 and R6, which may be the same or different, each represents hydrogen or C1-3alkyl); R2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R3 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X1 represents —O—, CH2—, —S—, —SO—, —SO2—, —NR7CO—, —CONR8—, —SO2NR9—, —NR10SO2— or —NR11— (wherein R7, R8, R9, R10 and R11 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl);R4 represents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted group selected from alkyl and a 5 or 6 membered saturated carbocyclic or heterocyclic group, and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

    摘要翻译： 本发明涉及式（I）的喹唑啉衍生物，其中m为1至2的整数; R 1表示氢，羟基，卤代，硝基，三氟甲基，氰基，C 1-3烷基，C 1-3烷氧基，C 1-3烷硫基或-NR 5 R 6（其中R 5和R 6） ，其可以相同或不同，各自表示氢或C 1-3烷基）; R 2表示氢，羟基，卤代，甲氧基，氨基或硝基; R 3表示羟基，卤代，C 1-3烷基，C 1-3烷氧基，C 1-3烷酰氧基，三氟甲基，氰基，氨基或硝基; X 1表示-O-，CH 2 - ， - S - ， - SO - ， - SO 2 - ， - NR 7 CO - ， - CONR 8 - ， - SO 2 NR 9 - SO 2 - 或-NR 11 - （其中R 7，R 8，R 9，R 10和R 11各自独立地表示氢，C 1-3烷基或C 1-3烷氧基C 2-3 - ）; R 4表示任选取代的5或6元饱和碳环或杂环基团或为烯基，炔基或任选取代的烷基的基团，该烷基可含有杂原子连接基团，该烯基，炔基或烷基可以 携带选自烷基和5或6元饱和碳环或杂环基的任选被取代的基团及其盐; 其制备方法，含有式（I）化合物或其药学上可接受的盐作为活性成分的药物组合物。 式（I）化合物及其药学上可接受的盐抑制VEGF在治疗许多疾病状态（包括癌症和类风湿性关节炎）中具有价值的性质。

    Cinnoline derivatives and use as medicine
    8.
    发明授权
    Cinnoline derivatives and use as medicine 失效
    噌啉衍生物用作药物

    公开(公告)号：US06514971B1

    公开(公告)日：2003-02-04

    申请号：US09142839

    申请日：1999-04-13

    申请人： Andrew Peter Thomas ,  Laurent Francois Andre Hennequin

    发明人： Andrew Peter Thomas ,  Laurent Francois Andre Hennequin

    IPC分类号： A61K31502

    CPC分类号： C07D401/12 ,  A61K31/502 ,  A61K31/5377 ,  C07D237/28 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12

    摘要： The invention relates to the use of cinnoline derivatives of formula (I) wherein Z represents —O—, —NH—, —S— or —CH2—; m is a n integer from 1 to 5; R1 represents hydrogen, hydroxy, halogeno, nitro, cyano, trifluoromethyl, Cp1-3alkyl, C1-3alkoxy, C1-3alkylthio or NR6R7 (wherein R6 and R7, which may be the same or different, each represents hydrogen or C1-3alkyl); R2 represents hydrogen, hydroxy, auoro, chioro, methoxy, amino or nitro; R3 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; R4 represents hydrogen, hydroxy, halogeno, cyano, nitro, amino, trifluoromethyl, C1-3alkyl or a group R5—X1 (wherein X1 represents —O—, —CH2—, —S—, —SO—, —SO2—, —NR8CO—, —CONR9—, —SO2NR10—, —NR11SO2— or NR12— (wherein R8, R9, R10, R11 and R12 each independently represents hydrogen, C1-3alkyl or C1-3alkoxy C2-3alkyl) and R5 is an optionally substituted alkyl, carbocylic or heterocylic group which may be saturated or unsaturated and may be directly linked to the cinnoline ring or be linked via a carbon chain which may have heteroatom linking groups within it and salts thereof, in the manufacture of a medicament for use in the production of an anti angiogenic and/or vascular permeability reducing effect in a warmn-blooded animal such as a human being, processes for the preparation of such derivatives, pharmnaceutical compositions containing a compound of formula (I) or a pharmnaceutically acceptable salt thereof as active ingredient and compounds of formula (I). The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

    摘要翻译： 本发明涉及式（I）的噌啉衍生物，其中Z表示-O - ， - NH - ， - S-或-CH 2 - ; m是1至5的n整数; R 1表示氢，羟基，卤代，硝基，氰基，三氟甲基，C 1-3烷基，C 1-3烷氧基，C 1-3烷硫基或NR 6 R 7（其中R 6和R 7可以相同或不同，各自表示氢或C 1-3烷基）。 R2代表氢，羟基，酰基，氯，甲氧基，氨基或硝基; R3表示羟基，卤代，C1-3烷基，C1-3烷氧基，C1-3烷酰氧基，三氟甲基，氰基，氨基或硝基; R 4表示氢，羟基，卤代，氰基，硝基，氨基，三氟甲基，C 1-3烷基或基团R 5 -X 1（其中X 1表示-O-，-CH 2 - ， - S - ， - SO-，-SO 2 - NR8CO-，-CONR9-，-SO2NR10-，-NR11SO2-或NR12-​​（其中R8，R9，R10，R11和R12各自独立地表示氢，C1-3烷基或C1-3烷氧基C2-3烷基），R5是任选取代的 烷基，碳环或杂环基团，其可以是饱和或不饱和的，并且可以直接连接到噌啉环，或者可以通过其中具有杂原子连接基团的碳链和其盐连接，制备用于 在温血动物例如人中产生抗血管生成和/或血管通透性降低作用，制备此类衍生物的方法，含有式（I）化合物或其药物上可接受的盐作为活性物质的药物组合物 成分和式（I）的化合物。式（I）的化合物 I）及其药学上可接受的盐抑制VEGF的作用，其在治疗许多疾病状态（包括癌症和类风湿性关节炎）中是有价值的。

    Oxindole derivatives
    10.
    发明授权
    Oxindole derivatives 失效
    羟吲哚衍生物

    公开(公告)号：US06265411B1

    公开(公告)日：2001-07-24

    申请号：US09180310

    申请日：1998-11-06

    申请人： Andrew Peter Thomas ,  Jean-Jacques Marcel Lohmann ,  Laurent Francois Andre Hennequin ,  Patrick Ple

    发明人： Andrew Peter Thomas ,  Jean-Jacques Marcel Lohmann ,  Laurent Francois Andre Hennequin ,  Patrick Ple

    IPC分类号： A61K31505

    CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14

    摘要： The invention relates to compounds of formula (I), wherein: R2 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino, nitro, C2-4alkanoyl, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylthio, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, {overscore (N)}—C1-4alkylcarbamoyl, {overscore (N)},{overscore (N)}-di(C1-4alkyl)carbamoyl, aminosulphonyl, {overscore (N)}—C1-4alkylaminosulphonyl, {overscore (N)},{overscore (N)}-di(C1-4alkyl)aminosulphonyl, C1-4alkylsulphonylamino, or a group R4X1 wherein X1 represents a direct bond, C2-4alkanoyl, —CONR5R6—, —SO2NR7R8— or —SO2R9— (wherein R5 and R7, each independently represents hydrogen or C1-2alkyl and R6, R8 and R9 each independently represents C1-4alkyl and wherein R4 is linked to R6, R8 or R9) and R4 represents an optionally substituted group selected from phenyl and a 5 or 6-membered heterocyclic group; n is an integer from 0 to 4, R1 represents hydrogen, C1-4alkyl, C1-4alkoxymethyl, di(C1-4alkoxy)methyl or C1-4alkanoyl; m is an integer from 0 to 4; and R3 represents hydroxy, halogeno, nitro, trifluoromethyl, C1-3alkyl, cyano, amino or R10X2 (wherein X2 represents a direct bond, —CH2—, or a single or double heteroatom linker group including —S—, —SO— and —NR15— (wherein R15 represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl), and R10 is an alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R10 is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF and FGF, properties of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

    摘要翻译： 本发明涉及式（I）化合物，其中：R 2表示羟基，卤代，C 1-3烷基，C 1-3烷氧基，C 1-3烷酰氧基，三氟甲基，氰基，氨基，硝基，C 2-4烷酰基，C 1-4烷酰基氨基，C 1-4烷氧基羰基 ，C 1-4烷硫基，C 1-4烷基亚磺酰基，C 1-4烷基磺酰基，氨基甲酰基，（超核（N）） - C 1-4烷基氨基甲酰基，{过核（N）}，{过核（N） （超核（N）） - C 1-4烷基氨基磺酰基，（超核（N）}，（超核（N）） - 二（C 1-4烷基）氨基磺酰基，C 1-4烷基磺酰基氨基或其中X 1表示直接键的基团R 4 X 1， 烷酰基，-CONR 5 R 6 - ，-SO 2 NR 7 R 8 - 或-SO 2 R 9 - （其中R 5和R 7各自独立地表示氢或C 1-2烷基，R 6，R 8和R 9各自独立地表示C 1-4烷基，并且其中R 4连接至R 6，R 8或R 9 ）和R 4表示选自苯基和5或6元杂环基的任选取代的基团; n为0至4的整数，R 1表示氢，C 1-4烷基，C 1-4烷氧基甲基，二（C 1-4烷氧基）甲基或C 1-4烷酰基; m为0〜4的整数; 并且R 3表示羟基，卤代，硝基，三氟甲基，C 1-3烷基，氰基，氨基或R 10 X 2（其中X 2表示直接键，-CH 2 - 或包含-S-，-SO-和 - NR15-（其中R15表示氢，C1-3烷基或C1-3烷氧基C2-3烷基），R10是任选被例如羟基，氨基，硝基，烷基，环烷基，烷氧基烷基或任选取代的基团选择性取代的烯基或炔基链