[发明专利]吡唑并[1,5-A]嘧啶的桥联双环杂环或螺双环杂环衍生物、其制备方法和用途无效
| 申请号: | 200980115328.5 | 申请日: | 2009-02-27 |
| 公开(公告)号: | CN102083835A | 公开(公告)日: | 2011-06-01 |
| 发明(设计)人: | 杰里米·I·莱文;达林·W·霍珀;南希·托里斯;米纽·D·杜蒂亚;丹·M·伯格;王晓*;马丁·J·迪格兰迪;张春春;亚历詹德罗·L·邓尼克 | 申请(专利权)人: | 惠氏有限责任公司 |
| 主分类号: | C07D491/20 | 分类号: | C07D491/20;A61K31/519;A61P35/00 |
| 代理公司: | 北京市柳沈律师事务所 11105 | 代理人: | 曹立莉 |
| 地址: | 美国新*** | 国省代码: | 美国;US |
| 权利要求书: | 查看更多 | 说明书: | 查看更多 |
| 摘要: | |||
| 搜索关键词: | 吡唑 嘧啶 桥联双环杂环 螺双环杂环 衍生物 制备 方法 用途 | ||
1.式A的化合物:
和其药学可接受的盐;
其中
R1是5-7元杂环或杂芳基环,所述环包含1-3个选自N、O或S的杂原子,并且所述环任选被一个至四个选自下列的取代基取代:-J,-NO2,-CN,-N3,-CHO,-CF3,-OCF3,-R7,-OR7,-S(O)mR7,-NR7R7,-NR7S(O)mR7,-OR9OR7,-OR9NR7R7,-N(R7)R9OR7,-N(R7)R9NR7R7,-NR7C(O)R7,-C(O)R7,-C(O)OR7,-C(O)NR7R7,-OC(O)R7,-OC(O)OR7,-OC(O)NR7R7,NR7C(O)R7,-NR7C(O)OR7,-NR7C(O)NR7R7,-R8OR7,-R8NR7R7,-R8S(O)mR7,-R8C(O)R7,-R8C(O)OR7,-R8C(O)NR7R7,-R8OC(O)R7,-R8OC(O)OR7,-R8OC(O)NR7R7,-R8NR7C(O)R7,-R8NR7C(O)OR7,-R8NR7C(O)NR7R7,-YR8R10,-YR8NR7R7和-YR10;
R2选自芳基环,9-14元双环芳基环,5-7元杂芳基环和9-14元双环杂芳基环,所述杂芳基环包含1-3个选自N、O和S的杂原子,所述环任选被一个至四个选自下列的取代基取代:-J,-NO2,-CN,-N3,-CHO,-CF3,-OCF3,-R7,-OR7,-S(O)mR7,-NR7R7,-NR7S(O)mR7,-OR9OR7,-OR9NR7R7,-N(R7)R9OR7,-N(R7)R9NR7R7,-NR7C(O)R7,-C(O)R7,-C(O)OR7,-C(O)NR7R7,-OC(O)R7,-OC(O)OR7,-OC(O)NR7R7,NR7C(O)R7,-NR7C(O)OR7,-NR7C(O)NR7R7,-R8OR7,-R8NR7R7,-R8S(O)mR7,-R8C(O)R7,-R8C(O)OR7,-R8C(O)NR7R7,-R8OC(O)R7,-R8OC(O)OR7,-R8OC(O)NR7R7,-R8NR7C(O)R7,-R8NR7C(O)OR7,-R8NR7C(O)NR7R7,-OPO(OR7)2,-YR8R10,-YR8NR7R7和-YR10;
R3、R4和R5各自独立地选自:碳连接的R6,-X-W-R6,H,J,-C(O)OR7,-C(O)NR7R7,-NR7C(O)R7,-CN,1-6个碳原子的烷基,1-8个碳原子的支链烷基,3-10个碳的环烷基环,芳基环,5-7元杂环和5-10元杂芳基环,所述杂环或杂芳基环包含1-3个选自N、O或S的杂原子,所述1-6个碳原子的烷基、1-8个碳原子的支链烷基、芳基环、5-7元杂环和5-10元杂芳基环任选被一个至四个选自下列的取代基取代:-J,-NO2,-CN,-N3,-CHO,-CF3,-OCF3,-R7,-OR7,-S(O)mR7,-NR7R7,-NR7S(O)mR7,-OR9OR7,-OR9NR7R7,-N(R7)R9OR7,-N(R7)R9NR7R7,-NR7C(O)R7,-C(O)R7,-C(O)OR7,-C(O)NR7R7,-OC(O)R7,-OC(O)OR7,-OC(O)NR7R7,NR7C(O)R7,-NR7C(O)OR7,-NR7C(O)NR7R7,-R8OR7,-R8NR7R7,-R8S(O)mR7,-R8C(O)R7,-R8C(O)OR7,-R8C(O)NR7R7,-R8OC(O)R7,-R8OC(O)OR7,-R8OC(O)NR7R7,-R8NR7C(O)R7,-R8NR7C(O)OR7,-R8NR7C(O)NR7R7和YR10,其中R3、R4和R5中的至少一个包含R6;
R6是6-14元桥联的双环杂环或双环螺杂环,所述环任选被一个或多个选自下列的取代基取代:-J,-NO2,-CN,-N3,-CHO,-CF3,-OCF3,-R7,-OR7,-S(O)mR7,-NR7R7,-NR7S(O)mR7,-OR9OR7,-OR9NR7R7,-N(R7)R9OR7,-N(R7)R9NR7R7,-NR7C(O)R7,-C(O)R7,-C(O)OR7,-C(O)NR7R7,-OC(O)R7,-OC(O)OR7,-OC(O)NR7R7,NR7C(O)R7,-NR7C(O)OR7,-NR7C(O)NR7R7,-R8OR7,-R8NR7R7,-R8S(O)mR7,-R8C(O)R7,-R8C(O)OR7,-R8C(O)NR7R7,-R8OC(O)R7,-R8OC(O)OR7,-R8OC(O)NR7R7,-R8NR7C(O)R7,-R8NR7C(O)OR7或-R8NR7C(O)NR7R7和YR10;
R7是H,或独立地选自任选被一个至四个选自下列的取代基取代的1-6个碳原子的烷基,1-8个碳原子的支链烷基,2-6个碳原子的烯基,2-6个碳原子的炔基,芳基环和5-10元杂芳基环:-J,-NO2,-CN,-N3,-CHO,-CF3,-OCF3,-R,-OR,-S(O)mR,-NRR,-NRS(O)mR,-OR9OR,-OR9NRR,-N(R)R9OR,-N(R)R9NRR,-NRC(O)R,-C(O)R,-C(O)OR,-C(O)NRR,-OC(O)R,-OC(O)OR,-OC(O)NRR,NRC(O)R,-NRC(O)OR,-NRC(O)NRR,-R8OR,-R8NRR,-R8S(O)mR,-R8C(O)R,-R8C(O)OR,-R8C(O)NRR,-R8OC(O)R,-R8OC(O)OR,-R8OC(O)NRR,-R8NRC(O)R,-R8NRC(O)OR,-R8NRC(O)NRR和ZR10,其中R选自1-6个碳原子的烷基,1-8个碳原子的支链烷基,2-6个碳原子的烯基,2-6个碳原子的炔基,3-10个碳原子的环烷基,6-10个碳原子的芳基和6-10个原子的杂芳基,所述杂芳基包含1-3个选自N、O和S的杂原子;
R8是二价基团,其独立地选自1-6个碳原子的烷基,2-6个碳原子的烯基,2-6个碳原子的炔基,芳基,杂芳基,环烷基和环杂烷基;
R9独立地是2-6个碳原子的二价烷基;
R10独立地选自3-10个碳的环烷基环,3-10个碳的二环烷基环,芳基环,杂环,杂芳基环和与一个至三个芳基或杂芳基环稠合的杂芳基环,每个杂环或杂芳基环包含1-3个选自N、O和S的杂原子,每个任选被一个至四个选自下列的取代基取代:-H,-芳基,-CH2-芳基,-NH-芳基,-O-芳基,-S(O)m-芳基,-J,-NO2,-CN,-N3,-CHO,-CF3,-OCF3,-R7,-OR7,-S(O)mR7,-NR7R7,-NR7S(O)mR7,-OR9OR7,-OR9NR7R7,-N(R7)R9OR7,-N(R7)R9NR7R7,-NR7C(O)R7,-C(O)R7,-C(O)OR7,-C(O)NR7R7,-OC(O)R7,-OC(O)OR7,-OC(O)NR7R7,-NR7C(O)R7,-NR7C(O)OR7,-NR7C(O)NR7R7,-R8OR7,R8NR7R7,-R8S(O)mR7,-R8C(O)R7,-R8C(O)OR7,-R8C(O)NR7R7,-R8C(O)R7,-R8C(O)OR7,-R8C(O)NR7R7,-R8OC(O)R7,-R8OC(O)OR7,-R8OC(O)NR7R7,-R8NR7C(O)R7,-R8NR7C(O)OR7和-R8NR7C(O)NR7R7;
J是氟、氯、溴或碘;
m是0-2的整数;
Y是二价基团,其独立地选自键,1-6个碳原子的烷基,2-6个碳原子的烯基,2-6个碳原子的炔基,O和-NR7;
X选自二价的,1-6个碳原子的烷基,2-6个碳原子的烯基,2-6个碳原子的炔基,3-10个碳的环烷基环,3-10个碳的二环烷基环,芳基环,杂环和杂芳基环,每个杂环或杂芳基环包含1-3个选自N、O或S的杂原子;任选被一个至四个选自下列的取代基取代:-H,-芳基,-CH2-芳基,-NH-芳基,-O-芳基,-S(O)m-芳基,-J,-NO2,-CN,-N3,-CHO,-CF3,-OCF3,-R7,-OR7,-S(O)mR7,-NR7R7,-NR7S(O)mR7,-OR9OR7,-OR9NR7R7,-N(R7)R9OR7,-N(R7)R9NR7R7,-NR7C(O)R7,-C(O)R7,-C(O)OR7,-C(O)NR7R7,-OC(O)R7-,-OC(O)OR7,-OC(O)NR7R7,-NR7C(O)R7,-NR7C(O)OR7,-NR7C(O)NR7R7,-R8OR7,R8NR7R7,-R8S(O)mR7,-R8C(O)R7,-R8C(O)OR7,-R8C(O)NR7R7,-R8C(O)R7,-R8C(O)OR7,-R8C(O)NR7R7,-R8OC(O)R7,-R8OC(O)OR7,-R8OC(O)NR7R7,-R8NR7C(O)R7,-R8NR7C(O)OR7和-R8NR7C(O)NR7R7;
W选自键,Z,-OZ-,-ZO-,-S(O)mZ-,-S(O)2NR7Z-,-NR7S(O)mZ-,-NR7Z-,-ZNR7-,-C(O)Z-;-C(O)OZ-,-C(O)NR7Z-,-NR7C(O)Z-,-NR7C(O)NR7Z-,-OC(O)Z-,-NR7C(O)OZ-和-OC(O)NR7Z-;和
Z是键或1-6个碳原子的二价烷基。
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