N-carbamimidoyl-4-[4-(furan-2-carbonyl)piperazin-1-yl]-3-methylsulfonylbenzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-carbamimidoyl-4-[4-(furan-2-carbonyl)piperazin-1-yl]-3-methylsulfonylbenzamide
• 化学式: C₁₈H₂₁N₅O₅S
• 分子量: 419.5
• InChiKey: JNHYDEHWSZINBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  161
• 氢给体数：
  2
• 氢受体数：
  6

文献信息

• Combination therapy involving a sodium-hydrogen exchanger type 1 or NHE-1 inhibitor for use in treatment of ischemia
  申请人：Pfizer Products Inc.

  公开号：EP1226830A2

  公开（公告）日：2002-07-31

  The invention provdes methods of reducing tissue damage resulting from ischemia which comprise administering to a mammal in need of such reduction an effective amount of a combination, or a pharmaceutical composition comprising such combination, of an NHE-1 inhibitor and a second compound selected from the group consisting of: (a) a complement modulator, (b) a metabolic modulator, (c) an anti-apoptotic agent, (d) a nitric oxide synthase-related agent, and (e) an enzyme/protein modulator. The invention further provides pharmaceutical compositions comprising an amount of an NHE-1 inhibitor; an amount of a second compound selected from the group consisting of (a) a complement modulator, (b) a metabolic modulator, (c) an anti-apoptotic agent, (d) a nitric oxide synthase-related agent, and an enzyme/protein modulator selected from the group consisting of a protein kinase C activator, an endothelin converting enzyme inhibitor, a thrombin-activatable fibrinolysis inhibitor (TAFI) inhibitor, an activated thrombin-activatable fibrinolysis inhibitor (TAFIa) inhibitor, a Na+/Ca+2 exchanger isoform-1 (NCX-1) inhibitor, and a poly (ADP ribose) synthetase (PARS/PARP) inhibitor; and, preferably, a pharmaceutically acceptable pharmaceutically acceptable carrier, vehicle, or diluent. The invention further provides kits comprising an amount of a sodium-hydrogen exchanger type-1 inhibitor, and a pharmaceutically acceptable carrier, vehicle, or diluent in a first unit dosage form; an amount of a second compound selected from the group consisting of (a) a complement modulator, (b) a metabolic modulator, (c) an anti-apoptotic agent, (d) a nitric oxide synthase-related agent, and (e) an enzyme/protein modulator selected from the group consisting of a protein kinase C activator, an endothelin converting enzyme inhibitor, a thrombin-activatable fibrinolysis inhibitor (TAFI) inhibitor, an activated thrombin-activatable fibrinolysis inhibitor (TAFIa) inhibitor, a Na+/Ca+2 exchanger isoform-1 (NCX-1) inhibitor, and a poly (ADP ribose) synthetase (PARS/PARP) inhibitor, and a pharmaceutically acceptable carrier, vehicle, or diluent in a second unit dosage form; and a container.

  本发明提供了减少缺血导致的组织损伤的方法，该方法包括向需要减少损伤的哺乳动物施用有效量的 NHE-1 抑制剂和选自以下组别的第二种化合物的组合或包含这种组合的药物组合物：(a) 补体调节剂，(b) 代谢调节剂，(c) 抗凋亡剂，(d) 一氧化氮合酶相关剂，和 (e) 酶/蛋白调节剂。本发明进一步提供了药物组合物，其中包含一定量的 NHE-1 抑制剂；一定量的选自以下组别的第二种化合物：(a) 补体调节剂；(b) 代谢调节剂；(c) 抗凋亡剂；(d) 一氧化氮合酶相关剂；以及选自以下组别的酶/蛋白调节剂：蛋白激酶 C 激活剂、内皮素转换酶抑制剂、凝血酶活化性纤维蛋白溶解抑制剂（TAFI）抑制剂、活化的凝血酶活化性纤维蛋白溶解抑制剂（TAFIa）抑制剂、Na+/Ca+2 交换异构体-1（NCX-1）抑制剂和多（ADP 核糖）合成酶（PARS/PARP）抑制剂；以及，优选药学上可接受的载体、载体或稀释剂。本发明进一步提供了包含一定量的钠-氢交换剂型-1 抑制剂和药学上可接受的载体、载体或稀释剂的试剂盒，试剂盒为第一单位剂型；一定量的选自以下组别的第二种化合物：(a) 补体调节剂；(b) 代谢调节剂；(c) 抗细胞凋亡剂；(d) 一氧化氮合酶相关剂；(e) 酶/蛋白调节剂，选自以下组别：蛋白激酶 C 激活剂；内皮素转换酶抑制剂；凝血酶激活的可凝血酶抑制剂、凝血酶活化性纤维蛋白溶解抑制剂（TAFI）抑制剂、活化的凝血酶活化性纤维蛋白溶解抑制剂（TAFIa）抑制剂、Na+/Ca+2 交换异构体-1（NCX-1）抑制剂和聚（ADP 核糖）合成酶（PARS/PARP）抑制剂，以及药学上可接受的载体、载体或稀释剂组成的组；以及一个容器。
• COMBINATION THERAPY
  申请人：——

  公开号：US20020099075A1

  公开（公告）日：2002-07-25

  The invention provdes methods of reducing tissue damage resulting from ischemia which comprise administering to a mammal in need of such reduction an effective amount of a combination, or a pharmaceutical composition comprising such combination, of an NHE-1 inhibitor and a second compound selected from the group consisting of: (a) a complement modulator, (b) a metabolic modulator, (c) an anti-apoptotic agent, (d) a nitric oxide synthase-related agent, and (e) an enzyme/protein modulator. The invention further provides pharmaceutical compositions comprising an amount of an NHE-1 inhibitor; an amount of a second compound selected from the group consisting of (a) a complement modulator, (b) a metabolic modulator, (c) an anti-apoptotic agent, (d) a nitric oxide synthase-related agent, and an enzyme/protein modulator selected from the group consisting of a protein kinase C activator, an endothelin converting enzyme inhibitor, a tissue-activated fibrinolytic inhibitor (TAFI), a Na + /Ca +2 exchanger isoform-1 (NCX-1) inhibitor, and a poly (ADP ribose) synthetase (PARS/PARP) inhibitor; and, preferably, a pharmaceutically acceptable pharmaceutically acceptable carrier, vehicle, or diluent. The invention further provides kits comprising an amount of a sodium-hydrogen exchanger type-1 inhibitor, and a pharmaceutically acceptable carrier, vehicle, or diluent in a first unit dosage form; an amount of a second compound selected from the group consisting of (a) a complement modulator, (b) a metabolic modulator, (c) an anti-apoptotic agent, (d) a nitric oxide synthase-related agent, and (e) an enzyme/protein modulator selected from the group consisting of a protein kinase C activator, an endothelin converting enzyme inhibitor, a tissue-activated fibrinolytic inhibitor (TAFI), a Na + /Ca +2 exchanger isoform-1 (NCX-1) inhibitor, and a poly (ADP ribose) synthetase (PARS/PARP) inhibitor, and a pharmaceutically acceptable carrier, vehicle, or diluent in a second unit dosage form; and a container.

  本发明提供了减少缺血导致的组织损伤的方法，该方法包括向需要减少损伤的哺乳动物施用有效量的NHE-1抑制剂和选自以下组的第二种化合物的组合或包含这种组合的药物组合物：(a)补体调节剂，(b)代谢调节剂，(c)抗细胞凋亡剂，(d)一氧化氮合酶相关剂，和(e)酶/蛋白调节剂。本发明进一步提供了药物组合物，该药物组合物包含一定量的 NHE-1 抑制剂；一定量的选自以下组别的第二种化合物：(a) 补体调节剂；(b) 代谢调节剂；(c) 抗细胞凋亡剂；(d) 一氧化氮合酶相关剂；以及选自以下组别的酶/蛋白质调节剂：蛋白激酶 C 激活剂、内皮素转换酶抑制剂、组织活化纤溶抑制剂 (TAFI)、Na. 加 /Ca 2 交换剂同工酶-1（NCX-1）抑制剂和聚（ADP 核糖）合成酶（PARS/PARP）抑制剂；以及，优选药学上可接受的载体、载体或稀释剂。本发明进一步提供了包含一定量的钠-氢交换机 1 型抑制剂和药学上可接受的载体、载体或稀释剂的试剂盒，试剂盒为第一单位剂型；一定量的选自以下组别的第二种化合物：(a) 补体调节剂；(b) 代谢调节剂；(c) 抗凋亡剂；(d) 一氧化氮合酶相关剂；(e) 酶/蛋白调节剂，选自以下组别：蛋白激酶 C 激活剂、内皮素转换酶抑制剂、组织活化纤溶抑制剂（TAFI）、Na 加 /Ca 2 交换剂同工酶-1（NCX-1）抑制剂和聚（ADP 核糖）合成酶（PARS/PARP）抑制剂，以及药学上可接受的载体、载体或稀释剂的第二单位剂型；和容器。
• VERFAHREN ZUR KRISTALLISATION VON GUANIDINIUM-SALZEN
  申请人：Merck Patent GmbH

  公开号：EP1620394B1

  公开（公告）日：2008-08-13
• Process for the crystallisation of guandinium salts
  申请人：Kirschbaum Michael

  公开号：US20070055064A1

  公开（公告）日：2007-03-08

  The invention relates to a process for the crystallisation of the compounds of the formula (I) or acid-addition salts thereof, in which R 1 , R 2 and R 3 have the meaning indicated in Claim 1 .
• METHODS AND COMPOSITIONS RELATING TO HEMATOLOGIC MALIGNANCIES
  申请人：Li Shaoguang

  公开号：US20120114605A1

  公开（公告）日：2012-05-10

  Methods of treating a subject having, or at risk of having, a myeloproliferative disorder are provided according to embodiments of the present invention which include administering a therapeutically effective amount of an arachidonate 5-lipoxygenase (5-LO) inhibitor to the subject. Combinations of therapeutic agents are administered according to embodiments of the present invention. In some embodiments, two or more 5-LO inhibitors are administered to a subject to treat a myeloproliferative disorder. In further embodiments, at least one 5-LO inhibitor and at least one additional therapeutic agent are administered to a subject to treat a myeloproliferative disorder. Methods of inhibiting leukemia stem cells are provided according to embodiments of the present invention which include contacting leukemia stem cells with an effective amount of an arachidonate 5-lipoxygenase inhibitor.