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1. 发明授权

US06262113B1 IL-8 receptor antagonists 失效
标题翻译： IL-8受体拮抗剂
公开(公告)号：US06262113B1
公开(公告)日：2001-07-17
申请号：US09125279
申请日：1998-08-14
申请人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Philip Hertzberg , Melvin Clarence Rutledge, Jr.
发明人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Philip Hertzberg , Melvin Clarence Rutledge, Jr.
IPC分类号： A61K31275
CPC分类号： A61K31/18 , A61K31/17 , A61K31/223 , A61K31/275 , A61K31/277 , A61K31/36 , A61K31/381 , A61K31/426 , A61K31/47 , C07C275/34 , C07C275/38 , C07C275/40 , C07C275/42 , C07C307/10 , C07C309/15 , C07C311/10 , C07C311/13 , C07C311/21 , C07C311/29 , C07C311/46 , C07C317/42 , C07C323/44 , C07C335/18 , C07C2602/08 , C07C2603/18 , C07D213/30 , C07D213/71 , C07D215/36 , C07D217/02 , C07D277/36 , C07D277/46 , C07D317/66 , C07D333/28 , C07D333/34 , C07D333/36 , C07D409/04 , Y02A50/411
摘要： The present invention relates to novel compounds and a novel use of phenyl ureas in the treatment of disease states mediated by the chemokine Interleukin-8 (IL-8).
摘要翻译：本发明涉及新化合物和苯尿脲在治疗由趋化因子白细胞介素-8（IL-8）介导的疾病状态中的新用途。

2. 发明授权

US06180675B2 IL-8 receptor antagonists 有权
标题翻译： IL-8受体拮抗剂
公开(公告)号：US06180675B2
公开(公告)日：2001-01-30
申请号：US09240354
申请日：1999-01-29
申请人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Philip Hertzberg , Melvin Clarence Rutledge, Jr.
发明人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Philip Hertzberg , Melvin Clarence Rutledge, Jr.
IPC分类号： A61K3117
CPC分类号： C07D213/30 , A61K31/17 , A61K31/18 , A61K31/223 , A61K31/275 , A61K31/277 , A61K31/36 , A61K31/381 , A61K31/426 , A61K31/47 , C07C275/34 , C07C275/38 , C07C275/40 , C07C275/42 , C07C307/10 , C07C309/15 , C07C311/10 , C07C311/13 , C07C311/21 , C07C311/29 , C07C311/46 , C07C317/42 , C07C323/44 , C07C335/18 , C07C2602/08 , C07C2603/18 , C07D213/71 , C07D215/36 , C07D217/02 , C07D277/36 , C07D277/46 , C07D317/66 , C07D333/28 , C07D333/34 , C07D333/36 , C07D409/04 , Y02A50/411
摘要： This invention relates to the novel use of phenyl ureas in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).
摘要翻译：本发明涉及苯脲类治疗由趋化因子介导的疾病状态，白细胞介素-8（IL-8）的新用途。

3. 发明授权

US5886044A IL-8 receptor antagonists 失效
标题翻译： IL-8受体拮抗剂
公开(公告)号：US5886044A
公开(公告)日：1999-03-23
申请号：US641990
申请日：1996-03-20
申请人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Phillip Hertzberg , Melvin Clarence Rutledge, Jr.
发明人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Phillip Hertzberg , Melvin Clarence Rutledge, Jr.
IPC分类号： A61K31/17 , A61K31/18 , A61K31/223 , A61K31/275 , A61K31/277 , A61K31/36 , A61K31/381 , A61K31/426 , A61K31/47 , A61P29/00 , A61P37/00 , C07C253/14 , C07C255/53 , C07C275/34 , C07C275/36 , C07C275/38 , C07C275/40 , C07C275/42 , C07C307/04 , C07C307/10 , C07C309/15 , C07C311/10 , C07C311/13 , C07C311/15 , C07C311/21 , C07C311/29 , C07C311/46 , C07C317/42 , C07C323/44 , C07C335/16 , C07C335/18 , C07D213/30 , C07D213/71 , C07D215/36 , C07D217/02 , C07D277/36 , C07D277/46 , C07D317/66 , C07D333/28 , C07D333/34 , C07D333/36 , C07D409/04
CPC分类号： C07D213/30 , A61K31/17 , A61K31/18 , A61K31/223 , A61K31/275 , A61K31/277 , A61K31/36 , A61K31/381 , A61K31/426 , A61K31/47 , C07C275/34 , C07C275/38 , C07C275/40 , C07C275/42 , C07C307/10 , C07C309/15 , C07C311/10 , C07C311/13 , C07C311/21 , C07C311/29 , C07C311/46 , C07C317/42 , C07C323/44 , C07C335/18 , C07D213/71 , C07D215/36 , C07D217/02 , C07D277/36 , C07D277/46 , C07D317/66 , C07D333/28 , C07D333/34 , C07D333/36 , C07D409/04 , C07C2102/08 , C07C2103/18
摘要： This invention relates to the novel use of phenyl ureas in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).
摘要翻译：本发明涉及苯脲类治疗由趋化因子介导的疾病状态，白细胞介素-8（IL-8）的新用途。

4. 发明授权

US06211373B1 Phenyl urea antagonists of the IL-8 receptor 失效
标题翻译：苯基脲拮抗剂的IL-8受体
公开(公告)号：US06211373B1
公开(公告)日：2001-04-03
申请号：US09111663
申请日：1998-07-08
申请人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Philip Hertzberg , Melvin Clarence Rutledge, Jr.
发明人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Philip Hertzberg , Melvin Clarence Rutledge, Jr.
IPC分类号： C07D33310
CPC分类号： A61K31/426 , A61K31/18 , A61K31/277 , A61K31/381 , A61K31/47 , Y02A50/411
摘要： 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.
摘要翻译：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。

5. 发明授权

US06005008A IL-8 receptor antagonists 失效
标题翻译： IL-8受体拮抗剂
公开(公告)号：US06005008A
公开(公告)日：1999-12-21
申请号：US894291
申请日：1997-08-15
申请人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Philip Hertzberg , Melvin Clarence Rutledge, Jr.
发明人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Philip Hertzberg , Melvin Clarence Rutledge, Jr.
IPC分类号： C07C275/34 , C07C275/40 , C07C275/42 , C07C311/13 , C07C311/14 , C07C311/21 , C07C311/29 , C07C311/44 , C07C311/46 , C07C317/42 , C07C323/44 , C07C335/18 , A61K31/17 , C07C273/00
CPC分类号： C07C311/29 , C07C275/34 , C07C275/40 , C07C275/42 , C07C311/13 , C07C311/14 , C07C311/21 , C07C311/44 , C07C311/46 , C07C317/42 , C07C323/44 , C07C335/18 , C07C2102/42 , C07C2103/18
摘要： This invention relates to the novel use of phenyl ureas in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).
摘要翻译： PCT No.PCT / US96 / 02260 Sec。 371日期：1997年8月15日 102（e）日期1997年8月15日PCT PCT 1996年2月16日PCT公布。公开号WO96 / 25157 日期1996年8月22日本发明涉及苯脲类治疗由趋化因子介导的疾病状态白细胞介素-8（IL-8）的新用途。

6. 发明授权

US5780483A IL-8 receptor antagonists 失效
标题翻译： IL-8受体拮抗剂
公开(公告)号：US5780483A
公开(公告)日：1998-07-14
申请号：US701299
申请日：1996-08-21
申请人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Philip Hertzberg , Melvin Clarence Rutledge, Jr.
发明人： Katherine Louisa Widdowson , Daniel Frank Veber , Anthony Joseph Jurewicz , Robert Philip Hertzberg , Melvin Clarence Rutledge, Jr.
IPC分类号： A61K31/17 , A61K31/18 , A61K31/223 , A61K31/275 , A61K31/277 , A61K31/36 , A61K31/381 , A61K31/426 , A61K31/47 , C07C275/34 , C07C275/38 , C07C275/40 , C07C275/42 , C07C307/10 , C07C309/15 , C07C311/10 , C07C311/13 , C07C311/21 , C07C311/29 , C07C311/46 , C07C317/42 , C07C323/44 , C07C335/18 , C07D213/30 , C07D213/71 , C07D215/36 , C07D217/02 , C07D277/36 , C07D277/46 , C07D317/66 , C07D333/28 , C07D333/34 , C07D333/36 , C07D409/04 , A61K31/425 , A61K31/38
CPC分类号： A61K31/17 , A61K31/18 , A61K31/223 , A61K31/275 , A61K31/277 , A61K31/36 , A61K31/381 , A61K31/426 , A61K31/47 , C07C275/34 , C07C275/38 , C07C275/40 , C07C275/42 , C07C307/10 , C07C309/15 , C07C311/10 , C07C311/13 , C07C311/21 , C07C311/29 , C07C311/46 , C07C317/42 , C07C323/44 , C07C335/18 , C07D213/30 , C07D213/71 , C07D215/36 , C07D217/02 , C07D277/36 , C07D277/46 , C07D317/66 , C07D333/28 , C07D333/34 , C07D333/36 , C07D409/04 , C07C2102/08 , C07C2103/18
摘要： This invention relates to novel compounds and a novel use of phenyl ureas in the treatment of disease scates mediated by the chemokine, Interleukin-8 (IL-8). In particular, this invention relates to the novel compounds of Formula (Ia) and their use in treating chemokine mediated diseases wherein the chemokine binds to an IL-8 a or b receptor. Compounds of Formula (Ia) are represented by the structure: ##STR1## wherein interalia, X is oxygen or sulfur; Rb is NR.sub.6 R.sub.7, alkcyl, aryl, arylC.sub.1-4 alkyl, aryl C.sub.2-4 alkenyl, heteroaryl, heteroarylC.sub.1-4 alkyl, heteroarylC.sub.2-4 alkenyl, heterocyclic or heterocyclic C.sub.1-4 alkyl, or a heterocyclic C.sub.2-4 alkenyl moiety, camphor, all of which may be optionally substituted; R.sub.1 is independently selected from hydrogen; halogen; nitro; cyano; C.sub.1-10 alkyl; halosubstituted C.sub.1-10 alkyl; C.sub.2-10 alkoxy; halosubstituted C.sub.1-10 alkoxy; azide; (CR.sub.8 R.sub.8)q S(O).sub.t R.sub.4 ; hydroxy; hydroxy substituted C.sub.1-4 alkyl; aryl; aryl C.sub.1-4 alkyl; aryl C.sub.2-10 alkenyl; aryloxy; aryl C.sub.1-4 alkyloxy; heteroaryl; heteroarylalkyl; heteroaryl C.sub.2-10 alkenyl; heteroaryl C.sub.1-4 alkyloxy; heterocyclic; heterocyclic C.sub.1-4 alkyl; heterocyclicC.sub.1-4 alkyloxy; heterocyclic C.sub.2-10 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; Y is hydrogen; halogen; nitro; cyano; halosubstituted C.sub.1-10 alkyl; C.sub.1-10 alkyl; C.sub.2-10 alkenyl C.sub.1-10 alkoxy; halosubstituted C.sub.1-10 alkoxy; azide; (CR.sub.8 R.sub.8)qS(O).sub.t R.sub.4, (CR.sub.8 R.sub.8)qOR.sub.4 ; hydorxy; hydroxy substituted C.sub.1-4 alkyl; aryl; aryl C.sub.1-4 alkyl; aryloxy; arylC.sub.1-4 alkyloxy; aryl C.sub.2-10 alkenyl; heteroaryl; heteroarylalkyl; heteroaryl C.sub.1-4 alkyloxy; heteroaryl C.sub.2-10 alkenyl; heterocyclic, heterocyclic C.sub.1-4 alkyl; heterocyclicC.sub.2-10 alkenyl; or a pharmaceutically acceptable salt thereof.
摘要翻译：本发明涉及新化合物和苯尿脲在治疗由趋化因子介导的疾病鳞状细胞白介素-8（IL-8）的新用途。特别地，本发明涉及式（Ia）的新化合物及其在治疗趋化因子介导的疾病中的用途，其中趋化因子与IL-8α或b受体结合。式（Ia）的化合物由以下结构表示：其中杂环，X是氧或硫; R b是NR 6 R 7，烷基，芳基，芳基C 1-4烷基，芳基C 2-4链烯基，杂芳基C 1-4烷基，杂芳基C 2-4链烯基，杂环或杂环C 1-4烷基或杂环C 2-4链烯基部分，樟脑，任选取代的; R 1独立地选自氢; 卤素; 硝基氰基; C 1-10烷基; 卤代C 1-10烷基; C 2-10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C2-10烯基; q为0或值为1〜10的整数; n为1〜3的整数， m为1〜3的整数， Y是氢; 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 1-10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; 芳氧基芳基C 1-4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。

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