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    Nitric oxide enhancing diuretic compounds, compositions and methods of use
    1.
    发明授权
    Nitric oxide enhancing diuretic compounds, compositions and methods of use 失效
    一氧化氮增强利尿剂，组合物和使用方法

    公开(公告)号：US07396829B2

    公开(公告)日：2008-07-08

    申请号：US11360599

    申请日：2006-02-24

    申请人： David S. Garvey ,  L. Gordon Letts ,  Richard A. Earl ,  Maiko Ezawa ,  Xinqin Fang ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

    发明人： David S. Garvey ,  L. Gordon Letts ,  Richard A. Earl ,  Maiko Ezawa ,  Xinqin Fang ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

    IPC分类号： C07D417/02 ,  A61K31/549

    CPC分类号： C07D285/30 ,  C07D285/28 ,  C07D285/32 ,  C07D417/04 ,  C07D417/06 ,  C07D513/10

    摘要： The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

    摘要翻译： 本发明描述了包含至少一种一氧化氮增强利尿剂或其药学上可接受的盐，和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新型组合物和试剂盒。 本发明还提供了（a）处理由过量水和/或电解质滞留导致的条件的方法; （二）治疗心血管疾病; （c）治疗血管性疾病; （d）治疗糖尿病; （e）治疗由氧化应激引起的疾病; （f）治疗内皮功能障碍; （g）治疗由内皮功能障碍引起的疾病; （h）治疗肝硬化; （j）治疗先兆子痫; （k）治疗骨质疏松症; （l）治疗肾病; （m）治疗外周血管疾病; （n）治疗门静脉高压; （o）治疗中枢神经系统疾病; （p）治疗代谢综合症; （q）治疗性功能障碍; 和（r）高脂血症。 一氧化氮增强利尿化合物包含通过一个或多个位点如碳，氧和/或氮通过不能水解的键或部分与利尿剂化合物连接的至少一个一氧化氮增强基团。

    Phenylpiperazine derivatives and their acid addition salts
    4.
    发明授权
    Phenylpiperazine derivatives and their acid addition salts 失效
    苯基哌嗪衍生物及其酸加成盐

    公开(公告)号：US4716161A

    公开(公告)日：1987-12-29

    申请号：US719456

    申请日：1985-04-03

    申请人： Harukazu Fukami ,  Ryoji Kikumoto ,  Kenichiro Nakao ,  Issei Nitta ,  Shinya Inoue

    发明人： Harukazu Fukami ,  Ryoji Kikumoto ,  Kenichiro Nakao ,  Issei Nitta ,  Shinya Inoue

    IPC分类号： C07D239/96 ,  C07D285/32 ,  C07D491/04 ,  C07D491/056 ,  C07D513/04 ,  A61K31/54 ,  C07D417/06

    CPC分类号： C07D491/04 ,  C07D239/96 ,  C07D285/32 ,  C07D513/04

    摘要： A phenylpiperazine derivative according to the present invention has the following general formula [I]: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are independently hydrogen or alkoxy group having 1 to 3 carbon atoms, orR.sup.1 and R.sup.2 or R.sup.2 and R.sup.3 together with carbon atoms to which they are attached form --O(CH.sub.2).sub.m O-- wherein m is an integer of 1 to 3, oreither R.sup.1 or R.sup.2 is amine residue selected from the group consisting of --NH.sub.2 , --NHSO.sub.2 CH.sub.3, --NHCOCH.sub.3 and --NHCONH.sub.2 and the other is hydrogen or alkoxy group of 1 to 3 carbon atoms and R.sup.3 is hydrogen;R.sup.4 and R.sup.5 are independently hydrogen or alkyl group of 1 to 3 carbon atoms;Y is --CO-- or --SO.sub.2 -- provided that at least one of R.sup.1 and R.sup.2 is not hydrogen when Y is --CO--; andn is an integer of 2 to 4.An acid addition salt of the phenylpiperazine derivative having the general formula [I] is included in the present invention. The phenylpiperazine derivative as well as its acid addition salt according to the present invention have the ability to reduce the blood pressure.

    摘要翻译： 根据本发明的苯基哌嗪衍生物具有以下通式[I]：其中R 1，R 2和R 3独立地是氢或具有1至3个碳原子的烷氧基，或者R 1和R 2或R 2和R 3 与其连接的碳原子一起形成-O（CH 2）m O-，其中m是1至3的整数，或者R 1或R 2是选自-NH 2，-NHSO 2 CH 3，-NHCOCH 3和 -NHCONH 2，另一个是1或3个碳原子的氢或烷氧基，R 3是氢; R4和R5独立地是氢或1〜3个碳原子的烷基; Y是-CO-或-SO 2 - ，条件是当Y是-CO-时，R 1和R 2中的至少一个不是氢; n为2〜4的整数。本发明包括具有通式[I]的苯基哌嗪衍生物的酸加成盐。 根据本发明的苯基哌嗪衍生物及其酸加成盐具有降低血压的能力。

    Nitric oxide enhancing diuretic compounds, compositions and methods of use
    6.
    发明申请
    Nitric oxide enhancing diuretic compounds, compositions and methods of use 失效
    一氧化氮增强利尿剂，组合物和使用方法

    公开(公告)号：US20060189603A1

    公开(公告)日：2006-08-24

    申请号：US11360599

    申请日：2006-02-24

    申请人： David Garvey ,  L. Letts ,  Richard Earl ,  Maiko Ezawa ,  Xinqin Fang ,  Ricky Gaston ,  Subhash Khanapure ,  Chia-En Lin ,  Ramani Ranatunge ,  Cheri Stevenson ,  Shiow-Jyi Wey

    发明人： David Garvey ,  L. Letts ,  Richard Earl ,  Maiko Ezawa ,  Xinqin Fang ,  Ricky Gaston ,  Subhash Khanapure ,  Chia-En Lin ,  Ramani Ranatunge ,  Cheri Stevenson ,  Shiow-Jyi Wey

    IPC分类号： A61K31/549 ,  C07D417/02

    CPC分类号： C07D285/30 ,  C07D285/28 ,  C07D285/32 ,  C07D417/04 ,  C07D417/06 ,  C07D513/10

    摘要： The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

    摘要翻译： 本发明描述了包含至少一种一氧化氮增强利尿剂或其药学上可接受的盐，和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新型组合物和试剂盒。 本发明还提供了（a）处理由过量水和/或电解质滞留导致的条件的方法; （二）治疗心血管疾病; （c）治疗血管性疾病; （d）治疗糖尿病; （e）治疗由氧化应激引起的疾病; （f）治疗内皮功能障碍; （g）治疗由内皮功能障碍引起的疾病; （h）治疗肝硬化; （j）治疗先兆子痫; （k）治疗骨质疏松症; （l）治疗肾病; （m）治疗外周血管疾病; （n）治疗门静脉高压; （o）治疗中枢神经系统疾病; （p）治疗代谢综合征; （q）治疗性功能障碍; 和（r）高脂血症。 一氧化氮增强利尿化合物包含通过一个或多个位点如碳，氧和/或氮通过不能水解的键或部分与利尿剂化合物连接的至少一个一氧化氮增强基团。

    Matrix metalloproteinase inhibitors
    7.
    发明申请
    Matrix metalloproteinase inhibitors 审中-公开
    基质金属蛋白酶抑制剂

    公开(公告)号：US20030078276A1

    公开(公告)日：2003-04-24

    申请号：US10075069

    申请日：2002-02-13

    发明人： Charles Andrianjara ,  Daniel Fred Ortwine ,  Alexander Gregory Pavlovsky ,  William Howard Roark

    IPC分类号： A61K031/517 ,  A61K031/47 ,  G06F019/00 ,  G01N033/48 ,  G01N033/50

    CPC分类号： C07D471/04 ,  A61K31/00 ,  C07C235/60 ,  C07D213/30 ,  C07D213/40 ,  C07D239/96 ,  C07D285/14 ,  C07D285/24 ,  C07D285/32 ,  C07D317/54 ,  C07D317/58 ,  C07D401/06 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/06 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D487/04 ,  C07D495/04 ,  C07D513/04

    摘要： Compounds are provided that bind allosterically to the catalytic domain of MMP-13 and comprise a hydrophobic group, first and second hydrogen bond acceptors and at least one, and preferably both, of a third hydrogen bond acceptor and a second hydrophobic group. Cartesian coordinates for centroids of the above features are defined in the specification. When the ligand binds to MMP-13, the first, second and third (when present) hydrogen bond acceptors bond respectively with Thr245, Thr 247 and Met 253, the first hydrophobic group locates within the S1null channel of MMP-13 and the second hydrophobic group (when present) is relatively open to solvent. The compounds specifically inhibit the matrix metalloproteinase-13 enzyme and thus are useful for treating diseases resulting from tissue breakdown, such as heart disease, multiple sclerosis, arthritis, atherosclerosis, and osteoporosis.

    摘要翻译： 提供化合物，其以构象方式与MMP-13的催化结构域结合，并且包含疏水基团，第一和第二氢键受体以及至少一个，优选两个第三氢键受体和第二疏水基团。 上述特征的质心的笛卡尔坐标在本说明书中定义。 当配体结合MMP-13时，第一，第二和第三（当存在）氢键受体分别与Thr245，Thr 247和Met 253键合时，第一个疏水基团位于MMP-13的S1'通道内，第二个 疏水基团（当存在时）对溶剂相对开放。 所述化合物特异性地抑制基质金属蛋白酶-13酶，因此可用于治疗由组织破坏引起的疾病，例如心脏病，多发性硬化，关节炎，动脉粥样硬化和骨质疏松症。

    Nitric oxide donating diuretic compounds, compositions and methods of use
    10.
    发明授权
    Nitric oxide donating diuretic compounds, compositions and methods of use 失效
    一氧化氮供应利尿剂，组合物和使用方法

    公开(公告)号：US07595313B2

    公开(公告)日：2009-09-29

    申请号：US12136531

    申请日：2008-06-10

    申请人： David S. Garvey ,  L. Gordon Letts ,  Richard A. Earl ,  Maiko Ezawa ,  Xinqin Fang ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

    发明人： David S. Garvey ,  L. Gordon Letts ,  Richard A. Earl ,  Maiko Ezawa ,  Xinqin Fang ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

    IPC分类号： C07D285/24 ,  C07D417/04 ,  C07D513/10 ,  A61K31/549

    CPC分类号： C07D285/30 ,  C07D285/28 ,  C07D285/32 ,  C07D417/04 ,  C07D417/06 ,  C07D513/10

    摘要： The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

    摘要翻译： 本发明描述了包含至少一种一氧化氮增强利尿剂或其药学上可接受的盐，和任选的至少一种一氧化氮增强化合物和/或至少一种治疗剂的新型组合物和试剂盒。 本发明还提供了（a）处理由过量水和/或电解质滞留导致的条件的方法; （二）治疗心血管疾病; （c）治疗血管性疾病; （d）治疗糖尿病; （e）治疗由氧化应激引起的疾病; （f）治疗内皮功能障碍; （g）治疗由内皮功能障碍引起的疾病; （h）治疗肝硬化; （j）治疗先兆子痫; （k）治疗骨质疏松症; （l）治疗肾病; （m）治疗外周血管疾病; （n）治疗门静脉高压; （o）治疗中枢神经系统疾病; （p）治疗代谢综合征; （q）治疗性功能障碍; 和（r）高脂血症。 一氧化氮增强利尿化合物包含通过一个或多个位点如碳，氧和/或氮通过不能水解的键或部分与利尿剂化合物连接的至少一个一氧化氮增强基团。