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公开(公告)号：US07173038B1
公开(公告)日：2007-02-06
申请号：US10129336
申请日：2000-11-01
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。
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公开(公告)号：US08642608B2
公开(公告)日：2014-02-04
申请号：US12761105
申请日：2010-04-15
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。
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3.发明申请公开(公告)号：US20110071144A1
公开(公告)日：2011-03-24
申请号：US12766106
申请日：2010-04-23
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： A61K31/517 , C07D239/94 , C07D405/12 , C07D403/12 , C07D413/12 , C07D401/12 , C07D417/12 , A61K31/5377 , A61K31/541 , A61K31/496 , A61P35/00 , A61P9/00
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。
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4.发明授权公开(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。
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公开(公告)号：US20110065736A1
公开(公告)日：2011-03-17
申请号：US12761105
申请日：2010-04-15
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。
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6.再颁专利公开(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。
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公开(公告)号：US06897210B2
公开(公告)日：2005-05-24
申请号：US10698388
申请日：2003-11-03
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： A61F13/00 , A61F13/02 , A61F13/15 , A61K20060101 , A61K31/505 , A61K31/517 , A61K31/5377 , A61K31/541 , A61P3/10 , A61P9/00 , A61P9/10 , A61P13/12 , A61P17/06 , A61P19/02 , A61P27/02 , A61P29/00 , A61P35/00 , A61P37/00 , A61P37/02 , A61P43/00 , C07D20060101 , C07D207/00 , C07D211/00 , C07D239/72 , C07D239/93 , C07D239/94 , C07D309/02 , C07D317/08 , C07D401/12 , C07D403/12 , C07D405/12 , C07D413/12 , C07D417/02 , C07D417/12 , A61K31/33
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 compostions 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 VEGP, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
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8.发明授权公开(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。
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公开(公告)号：US07160889B2
公开(公告)日：2007-01-09
申请号：US10240658
申请日：2001-04-03
IPC分类号： C07D239/00 , C07D239/70 , A01N47/40
CPC分类号： C07D401/12 , C07D239/94 , C07D403/12 , C07D417/12
摘要： The invention concerns quinazoline derivatives of Formula (I) wherein ring A is phenyl or a 5-or 6-membered heterocyclic ring which may be saturated, partially saturated or unsaturated and may be aromatic or non-aromatic and which contains 1, 2 or 3 ring heteroatoms selected from O, N and S; Z is —O—, —NH— or —S—; and X1, R1, R2, R3, m and R4 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in producing an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, and in the treatment of disease states such as cancer, rheumatoid arthritis and psorlasis.
摘要翻译： 本发明涉及式（I）的喹唑啉衍生物，其中环A是苯基或5-或6-元杂环，其可以是饱和的，部分饱和的或不饱和的，并且可以是芳族或非芳族的并且含有1,2或3 选自O，N和S的环杂原子; Z是-O - ， - NH-或-S-; 和X 1，R 1，R 2，R 3，m和R 4， SUP>具有描述中定义的任何含义; 其制备方法，含有它们的药物组合物及其在温血动物中产生抗血管生成和/或血管通透性降低作用的用途，以及治疗疾病状态如癌症，类风湿性关节炎和游丝氨酸酶的用途。
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公开(公告)号：US06514971B1
公开(公告)日：2003-02-04
申请号：US09142839
申请日：1999-04-13
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。
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