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    • 4. 发明授权
    • Phenyl urea antagonists of the IL-8 receptor
    • 苯基脲拮抗剂的IL-8受体
    • US06211373B1
    • 2001-04-03
    • US09111663
    • 1998-07-08
    • Katherine Louisa WiddowsonDaniel Frank VeberAnthony Joseph JurewiczRobert Philip HertzbergMelvin Clarence Rutledge, Jr.
    • Katherine Louisa WiddowsonDaniel Frank VeberAnthony Joseph JurewiczRobert Philip HertzbergMelvin Clarence Rutledge, Jr.
    • C07D33310
    • A61K31/426A61K31/18A61K31/277A61K31/381A61K31/47Y02A50/411
    • This invention relates to novel compounds of Formula (I), and a novel use of these compounds in treating chemokine mediated diseases, wherein the chemokine binds to an IL-8 a or b receptor. Compounds of Formula (1) are represented by the structure: wherein interalia, X is oxygen or sulfur; R is any functional moiety having an ionizable hydrogen and a pKa of 10 or less; R1 is independently selected from hydrogen; halogen; nitro; cyano; C1-C10 alkyl; halosubstituted C1-10 alkyl; C2-10 alkenyl; C1-10 alkoxy; halosubstituted C1-10 alkoxy; azide; (CR8R8)qS(O)tR4; hydroxy; hydroxy substituted C1-4 alkyl; aryl; aryl C1-4 alkyl; aryl C2-10 alkenyl; aryloxy; aryl C1-4 alkyloxy; heteroaryl; heteroarylalkyl; heteroaryl C2-10 alkenyl; heteroaryl C1-4 alkyloxy; heterocyclic, heterocyclic C1-4 alkyl; heterocyclic C1-4 alkyloxy; heterocyclic C2-10 alkenyl; q is 0 or an integer having a value of 1 to 10; n is an integer having a value of 1 to 3; m is an integer having a value of 1 to 3; n is an integer having a value of 1 to 3; Y is hydrogen; halogen; nitro; cyano; halosubstituted C1-10 alkyl; C1-10 alkyl; C2-10 alkenyl; C1-10 alkoxy; halosubstituted C1-1- alkoxy; azide; (CR8R8)qS(O)tR4, (CR8R8)qOR4; hydroxy; hydroxy substituted C1-4 alkyl; aryl; aryl C1-4 alkyl; aryloxy; aryC1-4 alkyloxy; aryl C2-10 alkenyl; heteroaryl; heteroarylalkyl; heteroaryl C1-4 alkyloxy; heteroaryl C2-10 alkenyl; heterocyclic, heterocyclic C1-4 alkyl; heterocyclic C2-10 alkenyl; or a pharmaceutically acceptable salt thereof.
    • 本发明涉及式(I)的新型化合物,以及这些化合物在治疗趋化因子介导的疾病中的新用途,其中趋化因子与IL-8α或b受体结合。 式(1)的化合物由以下结构表示:其中间隔,X是氧或硫; R是具有可电离的氢和pKa为10或更小的任何官能部分; R 1独立地选自氢; 卤素; 硝基 氰基; C1-C10烷基; 卤代C 1-10烷基; C 2-10烯基; C 1-10烷氧基; 卤代C 1-10烷氧基; 叠氮化物 (CR8R8)qS(O)tR4; 羟基; 羟基取代的C 1-4烷基; 芳基; 芳基C 1-4烷基; 芳基C2-10烯基; 芳氧基 芳基C 1-4烷氧基; 杂芳基; 杂芳基烷基; 杂芳基C2-10烯基; 杂芳基C 1-4烷氧基; 杂环,杂环C 1-4烷基; 杂环C 1-4烷氧基; 杂环C 2-10烯基; q为0或值为1至10的整数; n为1〜3的整数,m为1〜3的整数,n为1〜3的整数,Y为氢; 卤素; 硝基 氰基; 卤代C 1-10烷基; C 1-10烷基; C 2-10烯基; C 1-10烷氧基; 卤代C 1-1烷氧基; 叠氮化物 (CR8R8)qS(O)tR4,(CR8R8)qOR4; 羟基; 羟基取代的C 1-4烷基; 芳基; 芳基C 1-4烷基; 芳氧基 aryC1-4烷氧基; 芳基C2-10烯基; 杂芳基; 杂芳基烷基; 杂芳基C 1-4烷氧基; 杂芳基C2-10烯基; 杂环,杂环C 1-4烷基; 杂环C 2-10烯基;或其药学上可接受的盐。