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    Compounds and method for reducing uric acid
    1.
    发明授权
    Compounds and method for reducing uric acid 有权
    化合物和降低尿酸的方法

    公开(公告)号：US08829058B2

    公开(公告)日：2014-09-09

    申请号：US12920555

    申请日：2009-03-13

    申请人： James Dennen O'Neil ,  Michael K. Bamat ,  Reid W. von Borstel ,  Shalini Sharma ,  Ramachandran Arudchandran

    发明人： James Dennen O'Neil ,  Michael K. Bamat ,  Reid W. von Borstel ,  Shalini Sharma ,  Ramachandran Arudchandran

    IPC分类号： A01N31/14 ,  A61K31/075 ,  A01N35/00 ,  A61K31/12 ,  A01N31/08 ,  A61K31/05 ,  A01N37/10 ,  A61K31/195

    CPC分类号： C07C59/68 ,  A23G3/36 ,  A23G3/38 ,  A23G3/42 ,  A23G3/48 ,  A23G3/563 ,  A61K8/498 ,  A61K9/0056 ,  A61K31/192 ,  A61K31/216 ,  A61K31/352 ,  A61K31/704 ,  A61K45/06 ,  A61Q11/00 ,  C07C59/66 ,  C07C59/84 ,  C07C59/88 ,  C07C59/90 ,  C07C61/39 ,  C07C69/716 ,  C07C69/734 ,  C07C69/738 ,  C07C2601/02

    摘要： Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula I or a pharmaceutically acceptable salt thereof. In Formula I m is 0, 1, 2, 3 or 4; n is 0 or 1; t is 0 or 1; q is 0 or 1; and r is 0, 1 or 2. R6 is hydrogen, O or hydroxyl. R7 is hydrogen or alkyl having from 1 to 3 carbon atoms. One of R8 and R9 is alkyl having from 1 to 3 carbon atoms, and the other is hydrogen or alkyl having from 1 to 3 carbon atoms. R10 is hydrogen, halo, alkyl having from 1 to 3 carbon atoms or alkoxy having from 1 to 3 carbon atoms. X is C(O) and r is 0 and t is 0; or X is NH(R11) wherein R11 is hydrogen or alkyl having from 1 to 3 carbon atoms. A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, and perfluoromethoxy; or a 5 or 6 membered heteroaromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compound of Formula I by a ring carbon; or cycloalkyl having from 3 to 6 ring carbon atoms wherein the cycloalkyl is unsubstituted or one or two ring carbons are independently monosubstituted by methyl or ethyl. The uric acid-lowering effects of the Compounds of Formula I are used to treat or prevent a variety of conditions including gout, hyperuricemia, elevated levels of uric acid that do not meet the levels customarily justifying a diagnosis of hyperuricemia, renal dysfunction, kidney stones, cardiovascular disease, risk for developing cardiovascular disease, tumor-lysis syndrome, and cognitive impairment.

    摘要翻译： 减少哺乳动物受试者的尿酸，通过给予式I化合物或其药学上可接受的盐来增加尿酸的排泄。 在式I中，m为0,1,2,3或4; n为0或1; t为0或1; q为0或1; 并且r是0,1或2.R 6是氢，O或羟基。 R7是氢或具有1至3个碳原子的烷基。 R8和R9中的一个是具有1至3个碳原子的烷基，另一个是氢或具有1至3个碳原子的烷基。 R 10是氢，卤素，具有1至3个碳原子的烷基或具有1至3个碳原子的烷氧基。 X为C（O），r为0且t为0; 或X是NH（R 11），其中R 11是氢或具有1至3个碳原子的烷基。 A是未取代或被1或2个选自卤素，羟基，甲基，乙基，全氟甲基，甲氧基，乙氧基和全氟甲氧基的基团取代的苯基; 或具有1或2个选自N，S和O的环杂原子的5或6元杂芳环，杂芳环通过环碳与式I化合物的其余部分共价结合; 或具有3至6个环碳原子的环烷基，其中环烷基是未取代的或一个或两个环碳原子被甲基或乙基独立地单取代。 式I化合物的尿酸降低作用用于治疗或预防各种病症，包括痛风，高尿酸血症，升高的尿酸水平，不符合常规诊断高尿酸血症，肾功能不全，肾结石的水平 心血管疾病，发展心血管疾病的风险，肿瘤溶解综合征和认知障碍。

    Tetrazole compounds for reducing uric acid
    3.
    发明授权
    Tetrazole compounds for reducing uric acid 有权
    用于还原尿酸的四氮唑化合物

    公开(公告)号：US08410154B2

    公开(公告)日：2013-04-02

    申请号：US12989724

    申请日：2009-04-30

    申请人： James Dennen O'Neil ,  Shalini Sharma ,  Ramachandran Arudchandran

    发明人： James Dennen O'Neil ,  Shalini Sharma ,  Ramachandran Arudchandran

    IPC分类号： A61K31/41 ,  C07D257/04

    CPC分类号： C07D257/04 ,  A61K31/41 ,  A61K45/06

    摘要： Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula I. The uric acid-lowering effects of the compounds of this invention are used to treat or prevent a variety of conditions including gout, hyperuricemia, elevated levels of uric acid that do not meet the levels customarily justifying a diagnosis of hyperuricemia, renal dysfunction, kidney stones, cardiovascular disease, risk for developing cardiovascular disease, tumor-lysis syndrome, cognitive impairment, early-onset essential hypertension, and Plasmodium falciparum-induced inflammation. In Formula 1, x is 1 or 2: y is O, 1, 2 or 3; and R1 is selected from the group consisting of hydrogen, alkyl having 1 or 2 carbon atoms, hydroxy, alkoxy having 1 or 2 carbon atoms, fluoro, chloro, bromo, and amino. A is phenyl unsubstituted or substituted by one, two or three groups selected from the group consisting of halo, alkyl having 1 or 2 carbon atoms, perfluoromethyL alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy; or cycloalkyl having from 3 to 6 ring atoms wherein the cycloalky! is unsubstituted or one one two ring carbons are independently mono-substituted by methyl or ethyl; or a 5 or 6 membered heleraromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compound by a ring carbon.

    摘要翻译： 哺乳动物受试者中的尿酸通过给予式I化合物而降低尿酸的排泄。本发明化合物的尿酸降低作用用于治疗或预防多种病症，包括痛风，高尿酸血症，升高的 不符合常规诊断高尿酸血症，肾功能障碍，肾结石，心血管疾病，发展心血管疾病风险，肿瘤溶解综合征，认知障碍，早发性原发性高血压和恶性疟原虫的水平的尿酸水平， 诱发炎症。 在式1中，x是1或2：y是0,1,2或3; 并且R 1选自氢，具有1或2个碳原子的烷基，羟基，具有1或2个碳原子的烷氧基，氟，氯，溴和氨基。 A是未被取代或被选自卤素，具有1或2个碳原子的烷基，具有1或2个碳原子的全氟甲基烷氧基和全氟甲氧基的一个，两个或三个基团取代的苯基; 或具有3至6个环原子的环烷基，其中环烷基 是未取代的或一个二环碳独立地被甲基或乙基单取代; 或具有1或2个选自N，S和O的环杂原子的5或6元环状芳族环，杂芳环与环碳化合物的其余部分共价结合。

    TETRAZOLE COMPOUNDS FOR REDUCING URIC ACID
    4.
    发明申请
    TETRAZOLE COMPOUNDS FOR REDUCING URIC ACID 有权
    用于减少尿酸的四唑化合物

    公开(公告)号：US20110206653A1

    公开(公告)日：2011-08-25

    申请号：US12989724

    申请日：2009-04-30

    申请人： James Dennen O'Neil ,  Shalini Sharma ,  Ramachandran Arudchandran

    发明人： James Dennen O'Neil ,  Shalini Sharma ,  Ramachandran Arudchandran

    IPC分类号： A61K38/44 ,  C07D257/04 ,  A61K31/41 ,  A61P7/00 ,  A61P9/00 ,  A61P13/12 ,  A61P25/28 ,  A61P29/00

    CPC分类号： C07D257/04 ,  A61K31/41 ,  A61K45/06

    摘要： Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula I. The uric acid-lowering effects of the compounds of this invention are used to treat or prevent a variety of conditions including gout, hyperuricemia, elevated levels of uric acid that do not meet the levels customarily justifying a diagnosis of hyperuricemia, renal dysfunction, kidney stones, cardiovascular disease, risk for developing cardiovascular disease, tumor-lysis syndrome, cognitive impairment, early-onset essential hypertension, and Plasmodium falciparum-induced inflammation. In Formula 1, x is 1 or 2: y is O, 1, 2 or 3; and R1 is selected from the group consisting of hydrogen, alkyl having 1 or 2 carbon atoms, hydroxy, alkoxy having 1 or 2 carbon atoms, fluoro, chloro, bromo, and amino. A is phenyl unsubstituted or substituted by one, two or three groups selected from the group consisting of halo, alkyl having 1 or 2 carbon atoms, perfluoromethyL alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy; or cycloalkyl having from 3 to 6 ring atoms wherein the cycloalky! is unsubstituted or one one two ring carbons are independently mono-substituted by methyl or ethyl; or a 5 or 6 membered heleraromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compound by a ring carbon.

    摘要翻译： 哺乳动物受试者中的尿酸通过给予式I化合物而降低尿酸的排泄。本发明化合物的尿酸降低作用用于治疗或预防多种病症，包括痛风，高尿酸血症，升高的 不符合常规诊断高尿酸血症，肾功能障碍，肾结石，心血管疾病，发展心血管疾病风险，肿瘤溶解综合征，认知障碍，早发性原发性高血压和恶性疟原虫的水平的尿酸水平， 诱发炎症。 在式1中，x是1或2：y是0,1,2或3; 并且R 1选自氢，具有1或2个碳原子的烷基，羟基，具有1或2个碳原子的烷氧基，氟，氯，溴和氨基。 A是未被取代或被选自卤素，具有1或2个碳原子的烷基，具有1或2个碳原子的全氟甲基烷氧基和全氟甲氧基的一个，两个或三个基团取代的苯基; 或具有3至6个环原子的环烷基，其中环烷基 是未取代的或一个二环碳独立地被甲基或乙基单取代; 或具有1或2个选自N，S和O的环杂原子的5或6元环状芳族环，杂芳环与环碳化合物的其余部分共价结合。

    COMBINATION TREATMENT FOR METABOLIC DISORDERS
    5.
    发明申请
    COMBINATION TREATMENT FOR METABOLIC DISORDERS 审中-公开
    代谢障碍的组合治疗

    公开(公告)号：US20100227809A1

    公开(公告)日：2010-09-09

    申请号：US12377460

    申请日：2007-08-16

    申请人： Stephen D. Wolpe ,  Ramachandran Arudchandran ,  Reid W. von Borstel

    发明人： Stephen D. Wolpe ,  Ramachandran Arudchandran ,  Reid W. von Borstel

    IPC分类号： A61K38/17 ,  A61P3/00

    CPC分类号： A61K38/22 ,  A61K31/192 ,  A61K31/5377

    摘要： Various metabolic disorders, such as insulin resistance syndrome, diabetes, polycystic ovary syndrome, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis can be treated with a compound selected from an incretin mimetic and a dipeptidyl peptidase IV inhibitor in combination with a Compound of Formula, I or a pharmaceutically acceptable salt thereof, Formula (I) Three of R1, R2, R3, R4 and R5 are hydrogen and the remainder are independently selected from the group consisting of hydrogen, halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, and perfluoromethoxy; and m is 0, 2 or 4. R6 is hydrogen, O or hydroxy, and X is —OR7, wherein R7 is hydrogen or alkyl having from 1 to 3 carbon atoms; or R6 is hydrogen, and X is —NR8R9, wherein R8 is hydrogen or hydroxy and R9 is hydrogen, methyl or ethyl. When X is —NR8R9, hydroxy none of R1, R2, R3, R4 and R5 is hydroxy.

    摘要翻译： 可以用选自肠降血
    球蛋白模拟物和二肽基肽酶IV抑制剂的化合物与下列药物组合治疗各种代谢紊乱，例如胰岛素抵抗综合征，糖尿病，多囊卵巢综合征，高脂血症，脂肪肝疾病，恶病质，肥胖症，动脉粥样硬化和动脉硬化 式I的化合物或其药学上可接受的盐，式（I）R 1，R 2，R 3，R 4和R 5中的三个是氢，其余各自独立地选自氢，卤素，羟基，甲基，乙基， 全氟甲基，甲氧基，乙氧基和全氟甲氧基; R 6是氢，O或羟基，X是-OR 7，其中R 7是氢或具有1至3个碳原子的烷基; 或R6是氢，X是-NR8R9，其中R8是氢或羟基，R9是氢，甲基或乙基。 当X是-NR 8 R 9时，R 1，R 2，R 3，R 4和R 5不是羟基。