benzo[1,2,5]thiadiazole-5-carboxylic acid amide | 99620-31-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻二唑类
• 英文名称: benzo[1,2,5]thiadiazole-5-carboxylic acid amide
• 英文别名: Benzo[1,2,5]thiadiazol-5-carbonsaeure-amid；2,1,3-Benzothiadiazole-5-carboxamide
• CAS: 99620-31-2
• 化学式: C₇H₅N₃OS
• 分子量: 179.202
• InChiKey: BWYWVZZTHOLDGR-UHFFFAOYSA-N

物化性质

• 熔点：
  202-203 °C(Solv: water (7732-18-5))
• 沸点：
  405.7±18.0 °C(Predicted)
• 密度：
  1.516±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  97.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,1,3-苯并噻二唑-5-甲醛 在 sodium hydroxide 、 氯化亚砜 、 silver nitrate 作用下， 生成 benzo[1,2,5]thiadiazole-5-carboxylic acid amide
  参考文献：
  名称：

  Studies on the Antitubercular Compounds. XVI. Preparation of Some Derivatives of 2,1,3-Benzothiadiazole

  摘要：

  DOI：

  10.1246/bcsj.32.551

文献信息

• Pyridine matrix metalloproteinase inhibitors
  申请人：——

  公开号：US20020161000A1

  公开（公告）日：2002-10-31

  Selective MMP-13 inhibitors are pyridine derivatives of the formula 1 or a pharmaceutically acceptable salt thereof, wherein: R 1 and R 2 independently are hydrogen, halo, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, NO 2 , NR 4 R 5 , CN, or CF 3 , E is independently O or S; A and B independently are OR 4 or NR 4 R 5 ; R 4 and R 5 independently are H. C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, (CH 2 ) n aryl, (CH 2 ) n cycloalkyl, (CH 2 ) n heteroaryl, or R 4 and R 5 when taken together with the nitrogen to which they are attached complete a 3 to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NH, and optionally substituted or unsubstituted, n is an integer of from 0 to 6.

  选择性MMP-13抑制剂是符合以下结构式1的吡啶衍生物或其药用盐，其中： R1和R2独立地是氢、卤素、羟基、C1-C6烷基、C1-C6烷氧基、C2-C6烯基、C2-C6炔基、NO2、NR4R5、CN或CF3； E独立地是O或S； A和B独立地是OR4或NR4R5； R4和R5独立地是H、C1-C6烷基、C2-C6烯基、C2-C6炔基、(CH2)n芳基、(CH2)n环烷基、(CH2)n杂环芳基，或者R4和R5当与它们连接的氮一起形成含碳原子的3至8元环，可选地含有O、S或NH等杂原子，并可选择性地取代或未取代； n是0到6的整数。
• Combination of an allosteric carboxylic inhibitor of matrix metalloproteinase-13 with celecoxib or valdecoxib
  申请人：——

  公开号：US20040019053A1

  公开（公告）日：2004-01-29

  This invention provides a combination, comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with celecoxib, or a pharmaceutically acceptable salt thereof, or valdecoxib, or a pharmaceutically acceptable salt thereof. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with celecoxib, or a pharmaceutically acceptable salt thereof, or valdecoxib, or a pharmaceutically acceptable salt thereof. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with celecoxib, or a pharmaceutically acceptable salt thereof, or valdecoxib, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. The invention combination may also be further combined with other pharmaceutical agents depending on the disease being treated.

  该发明提供了一种组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，与Celecoxib或其药用盐，或Valdecoxib或其药用盐。该发明还提供了一种治疗对MMP-13和环氧合酶-2抑制敏感的疾病的方法，包括向患有这种疾病的患者施用包括MMP-13的变构羧酸抑制剂或其药用盐，与Celecoxib或其药用盐，或Valdecoxib或其药用盐的组合物。该发明还提供了一种药物组合物，包括包括MMP-13的变构羧酸抑制剂或其药用盐，与Celecoxib或其药用盐，或Valdecoxib或其药用盐的组合物，以及药用载体、稀释剂或赋形剂。该发明组合物还可以根据所治疗的疾病进一步与其他药物代理结合。
• Combination of an allosteric carboxylic inhibitor of matrix metalloproteinase-13 with a selective inhibitor of cyclooxygenase-2 that is not celecoxib or valdecoxib
  申请人：——

  公开号：US20040019054A1

  公开（公告）日：2004-01-29

  This invention provides a combination, comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with a selective inhibitor of COX-2, or a pharmaceutically acceptable salt thereof, that is not celecoxib or valdecoxib, and a pharmaceutically acceptable carrier, diluent, or excipient. This invention also provides a combination comprising an NSAID, or a pharmaceutically acceptable salt thereof, and an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof. This invention also provides a pharmaceutical composition, comprising the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent, or excipient. This invention also provides a method of treating a disease that is responsive to inhibition of MMP-13 and cyclooxygenase-1 or cyclooxygenase-2, comprising administering to a patient suffering from such a disease the invention combination comprising an allosteric carboxylic inhibitor of MMP-13, or a pharmaceutically acceptable salt thereof, with an NSAID, or a pharmaceutically acceptable salt thereof. The invention combinations may also be further combined with other pharmaceutical agents depending on the disease being treated.

  本发明提供一种组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，以及COX-2的选择性抑制剂或其药用盐，但不包括司来昔布或瓦来昔布。本发明还提供一种治疗对MMP-13和环氧合酶-2抑制响应的疾病的方法，包括向患有该疾病的患者施用包括MMP-13的变构羧酸抑制剂或其药用盐，以及COX-2的选择性抑制剂或其药用盐的本发明组合物，但不包括司来昔布或瓦来昔布。本发明还提供一种药物组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，以及COX-2的选择性抑制剂或其药用盐的本发明组合物，但不包括司来昔布或瓦来昔布，以及药用载体、稀释剂或赋形剂。本发明还提供一种组合物，包括NSAID或其药用盐，以及MMP-13的变构羧酸抑制剂或其药用盐。本发明还提供一种药物组合物，包括MMP-13的变构羧酸抑制剂或其药用盐，以及NSAID或其药用盐的本发明组合物，以及药用载体、稀释剂或赋形剂。本发明还提供一种治疗对MMP-13和环氧合酶-1或环氧合酶-2抑制响应的疾病的方法，包括向患有该疾病的患者施用包括MMP-13的变构羧酸抑制剂或其药用盐，以及NSAID或其药用盐的本发明组合物。根据所治疾病的不同，本发明组合物也可以与其他药物组合。
• Pyrimidine matrix metalloproteinase inhibitors
  申请人：——

  公开号：US20020151555A1

  公开（公告）日：2002-10-17

  Selective MMP-13 inhibitors are pyrimidine derivatives of the formula 1 or a pharmaceutically acceptable salt thereof, wherein: R 2 is hydrogen, halo, hydroxy, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, NO 2 , NR 4 R 5 , CN, or CF 3 ; E is independently O or S; A and B independently are OR 4 or NR 4 R 5 ; R 4 and R 5 independently are H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, (CH 2 ) n aryl, (CH 2 ) n cycloalkyl, (CH 2 )n heteroaryl, or R 4 and R 5 when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NH, and optionally substituted or unsubstituted; n is an integer of from 0 to 6.

  选择性MMP-13抑制剂是式1的嘧啶衍生物或其药学上可接受的盐，其中： R2是氢、卤素、羟基、C1-C6烷基、C1-C6烷氧基、C2-C6烯基、C2-C6炔基、NO2、NR4R5、CN或CF3； E独立地为O或S； A和B独立地为OR4或NR4R5； R4和R5独立地为H、C1-C6烷基、C2-C6烯基、C2-C6炔基、(CH2)n芳基、(CH2)n环烷基、(CH2)n杂环芳基，或者R4和R5在一起与它们所连接的氮形成一个含有碳原子并且可选地含有O、S或NH等杂原子的3-8元环，且可选地被取代或未取代； n为0至6的整数。
• Method of determining potential allosterically-binding matrix metalloproteinase inhibitors
  申请人：Andrianjara Charles

  公开号：US20050004126A1

  公开（公告）日：2005-01-06

  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 S1′ 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.

  提供了一种与MMP-13催化域发生变构作用的化合物，其中包括一个疏水基团、第一和第二氢键受体以及至少一个第三氢键受体和第二个疏水基团，最好是两者都有。上述特征的笛卡尔坐标在说明书中有定义。当配体与MMP-13结合时，第一、第二和第三（存在时）氢键受体分别与Thr245、Thr 247和Met 253结合，第一疏水基团位于MMP-13的S1'通道内，第二疏水基团（存在时）相对于溶剂较为开放。这些化合物特异性地抑制了基质金属蛋白酶-13酶，因此可用于治疗由组织分解引起的疾病，如心脏病、多发性硬化症、关节炎、动脉粥样硬化和骨质疏松症。