1-amino-5-hydroxymethyl-2-methoxypyridin-1-ium 2,4,6-trimethylbenzenesulfonate | 909717-77-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-amino-5-hydroxymethyl-2-methoxypyridin-1-ium 2,4,6-trimethylbenzenesulfonate
• 英文别名: 1-amino-5-hydroxymethyl-2-methoxypyridinium 2,4,6-trimethylbenzenesulfonate；1-Amino-5-hydroxymethyl-2-methoxypyridinium 2,4,6-trimethylbenzenesulfonate；(1-amino-6-methoxypyridin-1-ium-3-yl)methanol;2,4,6-trimethylbenzenesulfonate
• CAS: 909717-77-7
• 化学式: C₇H₁₁N₂O₂*C₉H₁₁O₃S
• 分子量: 354.427
• InChiKey: CDDGDENFSSKNCL-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  125
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-amino-5-hydroxymethyl-2-methoxypyridin-1-ium 2,4,6-trimethylbenzenesulfonate 在 manganese(IV) oxide 、 potassium carbonate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 邻二氯苯 为溶剂， 反应 43.0h， 生成 7-methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridine-4-carbaldehyde
  参考文献：
  名称：

  Phosphodiesterase inhibitors. Part 3: Design, synthesis and structure–activity relationships of dual PDE3/4-inhibitory fused bicyclic heteroaromatic-dihydropyridazinones with anti-inflammatory and bronchodilatory activity

  摘要：

  (-)-6-(7-甲氧基-2-三氟甲基嘌唑并[1,5-a]吡啶-4-基)-5-甲基-4,5-二氢-3-(2H)-吡啶嗪酮（KCA-1490）是一种 dual PDE3/4抑制剂，具有强大的联合支气管扩张和抗炎活性。对KCA-1490中嘌唑并[1,5-a]吡啶核心的潜在双环杂芳香族替换基团的调查已确定了4-甲氧基-2-(三氟甲基)苯并[d]噻唑-7-基和8-甲氧基-2-(三氟甲基)喹啉-5-基类似物作为 dual PDE3/4抑制剂，它们能有力地抑制组胺引起的支气管收缩，并在体内表现出抗炎活性。© 2012 Elsevier Ltd. 保留所有权利。

  DOI：

  10.1016/j.bmc.2012.01.033
• 作为产物：
  描述：

  O-(2,4,6-三甲基苯磺酰基)乙酰羟肟酸乙酯 在 高氯酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 1-amino-5-hydroxymethyl-2-methoxypyridin-1-ium 2,4,6-trimethylbenzenesulfonate
  参考文献：
  名称：

  Phosphodiesterase inhibitors. Part 3: Design, synthesis and structure–activity relationships of dual PDE3/4-inhibitory fused bicyclic heteroaromatic-dihydropyridazinones with anti-inflammatory and bronchodilatory activity

  摘要：

  (-)-6-(7-甲氧基-2-三氟甲基嘌唑并[1,5-a]吡啶-4-基)-5-甲基-4,5-二氢-3-(2H)-吡啶嗪酮（KCA-1490）是一种 dual PDE3/4抑制剂，具有强大的联合支气管扩张和抗炎活性。对KCA-1490中嘌唑并[1,5-a]吡啶核心的潜在双环杂芳香族替换基团的调查已确定了4-甲氧基-2-(三氟甲基)苯并[d]噻唑-7-基和8-甲氧基-2-(三氟甲基)喹啉-5-基类似物作为 dual PDE3/4抑制剂，它们能有力地抑制组胺引起的支气管收缩，并在体内表现出抗炎活性。© 2012 Elsevier Ltd. 保留所有权利。

  DOI：

  10.1016/j.bmc.2012.01.033

文献信息

• Phosphodiesterase inhibitors. Part 4: Design, synthesis and structure-activity relationships of dual PDE3/4-inhibitory fused bicyclic heteroaromatic-4,4-dimethylpyrazolones
  作者：Koji Ochiai、Satoshi Takita、Akihiko Kojima、Tomohiko Eiraku、Naoki Ando、Kazuhiko Iwase、Tetsuya Kishi、Akira Ohinata、Yuichi Yageta、Tokutaro Yasue、David R. Adams、Yasushi Kohno

  DOI：10.1016/j.bmcl.2012.07.088

  日期：2012.9

  (-)-6-(7-Methoxy-2-trifluoromethylpyrazolo[1,5-a]pyridin-4-yl)-5-methyl-4,5-dihydro-3-(2H)-pyridazinone (KCA-1490) is a dual PDE3/4 inhibitor that exhibits potent combined bronchodilatory and anti-inflammatory activity. Here we show that a 4,4-dimethylpyrazolone subunit serves as an effective surrogate for the 5-methyl-4,5-dihydropyridazin-3(2H)-one ring of KCA-1490 whilst lacking a stereogenic centre. The 2- and 7-substituents in the pyrazolo[1,5-a] pyridine subunit markedly influence the PDE-inhibitory profile and can be adjusted to afford either potent PDE4-selective inhibitors or dual PDE3/4 inhibitors. A survey of bicyclic heteroaromatic replacements for the pyrazolo[1,5-a] pyridine allowed further refinement of the inhibitory profile and identified 3-(8-methoxy-2-(trifluoromethyl) imidazo [1,2-a]pyridin-5-yl)-4,4-dimethyl-1H-pyrazol-5(4H)-one as an orally active, achiral KCA-1490 analog with well-balanced dual PDE3/4-inhibitory activity. (C) 2012 Elsevier Ltd. All rights reserved.

  (-)-6-(7-甲氧基-2-三氟甲基吡razolo[1,5-a]吡啶-4-基)-5-甲基-4,5-二氢-3-(2H)-吡啶嗪酮（KCA-1490）是一种双重PDE3/4抑制剂，表现出强大的联合支气管扩张和抗炎活性。在这里，我们展示了一个4,4-二甲基吡咯酮亚单元可以作为KCA-1490中5-甲基-4,5-二氢吡啶嗪-3(2H)-酮环的有效替代，同时缺乏一个手性中心。吡razolo[1,5-a]吡啶亚单元中的2-和7-取代基对PDE抑制活性谱有显著影响，并且可以进行调整，以获得效力较强的PDE4选择性抑制剂或双重PDE3/4抑制剂。对吡razolo[1,5-a]吡啶的双环杂环芳香族替代物的调查进一步优化了抑制活性，并确定了3-(8-甲氧基-2-(三氟甲基)咪唑并[1,2-a]吡啶-5-基)-4,4-二甲基-1H-吡咯-5(4H)-酮作为KCA-1490的一种活性良好的非手性、具有双重PDE3/4抑制活性均衡的口服活性类似物。(C) 2012 Elsevier Ltd. 保留所有权利。
• Pyrazolopyridine-4-Yl Pyridazinone Derivatives and Addition Salts Thereof, and Pde Inhibitors Comprising the Same Derivatives or Salts as Active Ingredient
  申请人：Kohno Yasushi

  公开号：US20080207902A1

  公开（公告）日：2008-08-28

  Novel pyrazolopyridine-4-yl pyridazinone derivatives serve as phosphodiesterase inhibitors and are useful compounds for use in pharmaceutical products. Specifically, the compounds of the present invention are pyrazolopyridine-4-yl pyridazinone derivatives represented by the following general formula (1): (Example: 6-(2-ethyl-7-methoxy-pyrazolo[1,5-a]pyridine-4-yl)-5-methyl-4, 5-dihydro-3(2H)-pyridazinone).

  新型吡唑吡啶-4-基吡啉酮衍生物作为磷酸二酯酶抑制剂，并且是用于制药产品的有用化合物。具体来说，本发明的化合物是由以下一般式（1）表示的吡唑吡啶-4-基吡啉酮衍生物（例如：6-(2-乙基-7-甲氧基吡唑并[1,5-a]吡啶-4-基)-5-甲基-4,5-二氢-3(2H)-吡啉酮）。
• Pyrazolopyride derivative and phosphodiesterase ( pde) inhibitors containing the same as active ingredient
  申请人：Kohno Yasushi

  公开号：US20090318385A1

  公开（公告）日：2009-12-24

  A novel pyrazolopyridine derivative is provided which is useful as a pharmaceutical drug having phosphodiesterase inhibitory activity. The pyrazolopyridine derivative is represented by the following general formula (1): [wherein R 1 is a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms, or the like, R 2 is an optionally substituted alkyl group having 1 to 6 carbon atoms or the like, R 5 and R 6 are independently a hydrogen atom or a halogen atom, R 13 is a hydrogen atom or a halogen atom, n is 0 or 1, is a single or double bond, R 3 is a hydrogen atom, a hydroxyl group, or the like, and R 4 is a hydrogen atom, a phenyl group, or the like] or a pharmaceutically acceptable salt thereof, and a hydrate thereof.

  提供了一种新的吡唑吡啶衍生物，其可用作具有磷酸二酯酶抑制活性的药物。该吡唑吡啶衍生物由以下通式（1）表示：[其中，R1是氢原子、1至6个碳原子的可选取代烷基或类似物，R2是1至6个碳原子的可选取代烷基或类似物，R5和R6独立地是氢原子或卤素原子，R13是氢原子或卤素原子，n为0或1，为单键或双键，R3是氢原子、羟基或类似物，R4是氢原子、苯基或类似物]或其药学上可接受的盐和水合物。
• Pyrazolopyridine carboxamide derivative and phosphodiesterase (pde) inhibitor containing the same
  申请人：Kohno Yasushi

  公开号：US20100056791A1

  公开（公告）日：2010-03-04

  A novel pyrazolopyridine carboxamide derivative is provided that is useful as a pharmaceutical drug having phosphodiesterase inhibitory activity. The pyrazolopyridine carboxamide derivative is represented by the following general formula (1): (Example: 2-ethyl-7-methoxypyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide).

  提供了一种新型的吡唑吡啶羧酰胺衍生物，其可用作具有磷酸二酯酶抑制活性的药物。该吡唑吡啶羧酰胺衍生物由以下通式（1）表示：（例如：2-乙基-7-甲氧基吡唑并[1,5-a]吡啶-4-羧酸（3,5-二氯吡啶-4-基）酰胺）。
• PYRAZOLOPYRIDINE CARBOXAMIDE DERIVATIVE AND PHOSPHODIESTERASE (PDE) INHIBITOR COMPRISING THE DERIVATIVE
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：EP2058310A1

  公开（公告）日：2009-05-13

  A novel pyrazolopyridine carboxamide derivative is provided that is useful as a pharmaceutical drug having phosphodiesterase inhibitory activity. The pyrazolopyridine carboxamide derivative is represented by the following general formula (1): (Example: 2-ethyl-7-methoxypyrazolo[1,5-a]pyridine-4-carboxylic acid (3,5-dichloropyridin-4-yl)amide).

  本研究提供了一种新型吡唑吡啶羧酰胺衍生物，可用作具有磷酸二酯酶抑制活性的药物。 吡唑吡啶羧酰胺衍生物由以下通式（1）表示： (例：2-乙基-7-甲氧基吡唑并[1,5-a]吡啶-4-羧酸（3,5-二氯吡啶-4-基）酰胺）。