6-(7-methoxy-2-(trifluoromethyl)benzo[d]oxazol-4-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one | 1013037-11-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 6-(7-methoxy-2-(trifluoromethyl)benzo[d]oxazol-4-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one
• 英文别名: 6-(7-methoxy-2-trifluoromethylbenzooxazol-4-yl)-4,5-dihydro-5-methyl-3-(2H)-pyridazinone；3-[2-(Trifluoromethyl)-7-methoxybenzoxazole-4-yl]-4-methyl-4,5-dihydropyridazine-6(1H)-one；3-[7-methoxy-2-(trifluoromethyl)-1,3-benzoxazol-4-yl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one
• CAS: 1013037-11-0
• 化学式: C₁₄H₁₂F₃N₃O₃
• 分子量: 327.263
• InChiKey: XIHOEZMXTDWCMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-氨基-6-甲氧基苯酚 在 肼基甲酸叔丁酯 、 四氯化钛 、 sodium hydride 、 对甲苯磺酸 、 三氟乙酸 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 83.5h， 生成 6-(7-methoxy-2-(trifluoromethyl)benzo[d]oxazol-4-yl)-5-methyl-4,5-dihydropyridazin-3(2H)-one
  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

• PYRIDAZINONE DERIVATIVE AND PDE INHIBITOR CONTAINING THE SAME AS ACTIVE INGREDIENT
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：EP2168959A1

  公开（公告）日：2010-03-31

  It is to provide a novel pyridazinone derivative represented by the following general formula (1), which is useful as a pharmaceutical and has a phosphodiesterase inhibitory action: wherein R1 represents H or C1-6 alkyl, each of R2 and R3 represents H, X, C1-6 alkoxy, Z represents O or S, and A represents AA or BB, wherein AA represents: and BB represents: wherein R4 represents H or C1-6 alkyl, and each of R5 and R6 represents C1-6 alkyl.

  提供一种新颖的吡啶并酮衍生物，其通式如下（1），可用作药物，并具有磷酸二酯酶抑制作用： 其中R1代表H或C1-6烷基，R2和R3各自代表H、X、C1-6烷氧基，Z代表O或S，A代表AA或BB，其中AA代表： 而BB代表： 其中R4代表H或C1-6烷基，R5和R6各自代表C1-6烷基。
• An Improved Method for Synthesis of 4,4-Dimethylpyrazolone and Application to Dihydropyridazinone Ring Formation
  作者：Koji Ochiai、Akihiko Kojima、Yasushi Kohno

  DOI：10.1248/cpb.60.267

  日期：——

  An improved method for 4,4-dimethylpyrazolone synthesis with t-butylcarbazate was described. The applicability of this method to dihydropyridazinone formation was demonstrated. This method is useful for suppressing the side reaction caused by the high nucleophilicity of hydrazine.

  描述了一种用氨基甲酸叔丁酯合成4,4-二甲基吡唑酮的改进方法。证明了该方法对二氢哒嗪酮形成的适用性。该方法对于抑制由肼的高亲核性引起的副反应是有用的。
• 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
  作者：Koji Ochiai、Satoshi Takita、Tomohiko Eiraku、Akihiko Kojima、Kazuhiko Iwase、Tetsuya Kishi、Kazunori Fukuchi、Tokutaro Yasue、David R. Adams、Robert W. Allcock、Zhong Jiang、Yasushi Kohno

  DOI：10.1016/j.bmc.2012.01.033

  日期：2012.3

  (-)-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. A survey of potential bicyclic heteroaromatic replacement subunits for the pyrazolo[1,5-a] pyridine core of KCA-1490 has identified the 4-methoxy-2-(trifluoromethyl)benzo[d] thiazol-7-yl and 8-methoxy-2-(trifluoromethyl)quinolin-5-yl analogues as dual PDE3/4-inhibitory compounds that potently suppress histamine-induced bronchoconstriction and exhibit anti-inflammatory activity in vivo. (C) 2012 Elsevier Ltd. All rights reserved.

  (-)-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。