6-(trifluoromethyl)-2,3-dihydrophthalazine-1,4-dione | 26238-15-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-(trifluoromethyl)-2,3-dihydrophthalazine-1,4-dione
• CAS: 26238-15-3
• 化学式: C₉H₅F₃N₂O₂
• 分子量: 230.146
• InChiKey: IDLVHYJXEWYMIZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.486±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(trifluoromethyl)-2,3-dihydrophthalazine-1,4-dione 在 三氯氧磷 作用下， 以64.02 %的产率得到1,4-二氯-6-(三氟甲基)酞嗪
  参考文献：
  名称：

  一类取代杂芳酞嗪衍生物的药学用途及其制备方法

  摘要：

  本公开涉及一种如式(I‑0)所示的取代杂芳酞嗪衍生物，其作为NLRP3抑制剂的用途及制备方法，其具有较好的NLRP3抑制活性。

  公开号：

  CN115417856A
• 作为产物：
  描述：

  5-(三氟甲基)异吲哚啉-1,3-二酮 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 6-(trifluoromethyl)-2,3-dihydrophthalazine-1,4-dione
  参考文献：
  名称：

  4-Benzylamino-1-chloro-6-substituted Phthalazines:  Synthesis and Inhibitory Activity toward Phosphodiesterase 5

  摘要：

  We synthesized various 4-benzylamino-1-chloro-6-substituted phthalazines (15) and 4-benzylamino-1-chloro-7-substituted phthalazines (16) and evaluated their inhibitory activity toward phosphodiesterase 5 (PDE5) purified from porcine platelets. The PDE5-inhibitory activities of 15 were greater than those of the isomers (16). The preferred substituent at the 4-position of phthalazine was a (3-chloro-4-methoxybenzyl)amino group, and those at the B-position were cyano, nitro, and trifluoromethyl groups. Compounds 15a (IC50 = 4.8 nM), 15f (3.5 nM), and 15i (5.3 nM) were more potent inhibitors than E4021 (8.6 nM). Compounds 15a and 15f also showed vasorelaxant activity in isolated porcine coronary arteries precontracted with prostaglandin F-2 alpha (10(-5) M). The EC50 values for vasorelaxant action of 15a, 15f, and E4021 were 150, 160, and 980 nM, respectively. These results show that novel PDE5 inhibitors possessing a potent vasorelaxant effect may exist among phthalazine derivatives.

  DOI：

  10.1021/jm970815r

文献信息

• 一类取代杂芳酞嗪衍生物的药学用途及其制备方法
  申请人：成都奥睿药业有限公司

  公开号：CN115417856A

  公开（公告）日：2022-12-02

  本公开涉及一种如式(I‑0)所示的取代杂芳酞嗪衍生物，其作为NLRP3抑制剂的用途及制备方法，其具有较好的NLRP3抑制活性。
• Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model
  作者：Maud Bollenbach、Claire Lugnier、Mélanie Kremer、Eric Salvat、Salim Megat、Frédéric Bihel、Jean-Jacques Bourguignon、Michel Barrot、Martine Schmitt

  DOI：10.1016/j.ejmech.2019.05.026

  日期：2019.9

  Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50=3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole) were evaluated in comparison to MY 5445 (4b) in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment. (C) 2019 Elsevier Masson SAS. All rights reserved.
• 4-Benzylamino-1-chloro-6-substituted Phthalazines:  Synthesis and Inhibitory Activity toward Phosphodiesterase 5
  作者：Nobuhisa Watanabe、Yasuhiro Kabasawa、Yasutaka Takase、Masayuki Matsukura、Kazuki Miyazaki、Hiroki Ishihara、Kohtarou Kodama、Hideyuki Adachi

  DOI：10.1021/jm970815r

  日期：1998.8.1

  We synthesized various 4-benzylamino-1-chloro-6-substituted phthalazines (15) and 4-benzylamino-1-chloro-7-substituted phthalazines (16) and evaluated their inhibitory activity toward phosphodiesterase 5 (PDE5) purified from porcine platelets. The PDE5-inhibitory activities of 15 were greater than those of the isomers (16). The preferred substituent at the 4-position of phthalazine was a (3-chloro-4-methoxybenzyl)amino group, and those at the B-position were cyano, nitro, and trifluoromethyl groups. Compounds 15a (IC50 = 4.8 nM), 15f (3.5 nM), and 15i (5.3 nM) were more potent inhibitors than E4021 (8.6 nM). Compounds 15a and 15f also showed vasorelaxant activity in isolated porcine coronary arteries precontracted with prostaglandin F-2 alpha (10(-5) M). The EC50 values for vasorelaxant action of 15a, 15f, and E4021 were 150, 160, and 980 nM, respectively. These results show that novel PDE5 inhibitors possessing a potent vasorelaxant effect may exist among phthalazine derivatives.