1-hydroxy-4-(3-pyridyl)phthalazine | 75884-68-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-hydroxy-4-(3-pyridyl)phthalazine
• 英文别名: 4-(3-pyridyl)phthalazin-1(2H)-one；4-pyridin-3-yl-2H-phthalazin-1-one
• CAS: 75884-68-3
• 化学式: C₁₃H₉N₃O
• 分子量: 223.234
• InChiKey: HZYDLUINYUTSDC-UHFFFAOYSA-N

物化性质

• 熔点：
  269-270 °C
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-hydroxy-4-(3-pyridyl)phthalazine 在 sodium hydroxide 、 五氯化磷 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 5.75h， 生成 2-<3-<(N-isopropylamino)carbonyl>propyl>-4-(3-pyridyl)-1(2H)-phthalazinone
  参考文献：
  名称：

  Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 2. 4-(3-Pyridyl)-1(2H)-phthalazinones

  摘要：

  A series of novel 4-(3-pyridyl)-1(2H)-phthalazinone derivatives which possess dual activities of thromboxane A(2) (TXA(2)) synthetase inhibition and bronchodilation was synthesized, and their pharmacological activities were evaluated. While the length and the built of 2-alkyl substituents had no influence on either activity, the 2-substituents with polar groups reduced bronchodilatory activity. Furthermore, we introduced heteroaromatic nuclei into the 4-position of the phthalazinone and found that 1-imidazolyl (13a) and 5-thiazolyl (16b and 16c) derivatives were as active as the parent 3-pyridyl compound 5b. These findings suggest that heteroaromatic nuclei at the Li-position of phthalazinones play a critical role in TXA(2) synthetase inhibition, Additionally, the hydrophobicity of the compounds was found to exert a marked influence on bronchodilatory activity. These observations led to the selection of 2-ethyl-4-(3-pyridyl)-1 (2H)-phthalazinone (5b) (KK-505) and 2-methyl-4-(5-thiazolyl)-1(2H)-phthalazinone (16b) (KK-562) for further studies. Although their precise mechanism of action remains unclear, this series of novel phthalazinone derivatives represents a new class of antiasthma agents with dual activities.

  DOI：

  10.1021/jm00077a009
• 作为产物：
  描述：

  2-溴苯甲酸 在 正丁基锂 、 一水合肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 8.5h， 生成 1-hydroxy-4-(3-pyridyl)phthalazine
  参考文献：
  名称：

  4-Heteroaryl Phthalazin-1(2H)-one Derivatives as Potent Melanin Concentrating Hormone Receptor 1 (MCH-R1) Antagonists

  摘要：

  DOI：

  10.5012/bkcs.2012.33.7.2389

文献信息

• Pyridine derivatives
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US05965730A1

  公开（公告）日：1999-10-12

  A pyridine derivative of the formula (I): ##STR1## wherein A is group of the following formulae: ##STR2## (R.sup.1 and R.sup.2 are each H, or protected or unprotected OH, R.sup.31, R.sup.41 and R.sup.42 are protected or unprotected hydroxymethyl, R.sup.32 is H, lower alkyl, or protected or unprotected hydroxymethyl, R.sup.33 is substituted or unsubstituted lower alkyl, and the dotted line means the presence or absence of a double bond), R.sup.5 and R.sup.6 are H, or protected or unprotected amino, or both combine together with the adjacent nitrogen to form substituted or unsubstituted heterocycle, or a pharmaceutically acceptable salt thereof, these compounds showing excellent bronchoconstriction inhibitory activity and/or anti-inflammatory activity of airway, and being useful in the prophylaxis or treatment of asthma.

  化合物的化学式（I）的吡啶衍生物：其中A是以下化学式的基团：（R.sup.1和R.sup.2分别为H，或受保护或未受保护的OH，R.sup.31、R.sup.41和R.sup.42为受保护或未受保护的羟甲基，R.sup.32为H，较低的烷基，或受保护或未受保护的羟甲基，R.sup.33为取代或未取代的较低烷基，虚线表示双键的存在或不存在），R.sup.5和R.sup.6为H，或受保护或未受保护的氨基，或两者结合在一起与相邻的氮形成取代或未取代的杂环，或其药学上可接受的盐，这些化合物表现出出色的支气管收缩抑制活性和/或气道抗炎活性，并且在哮喘的预防或治疗中有用。
• Application of Organolithium and Related Reagents in Synthesis. Part 22¹. Synthetic Strategies Based on Ortho-Aromatic Metallation. A Concise Regiospecific Conversion of Benzoic Acids into the 4-Pyridyl-2<i>H</i>-Phthalazin-1-Ones
  作者：J. Z. Brzezinski、J. Epsztajn、A. D. Bakalarz、A. Lajszczak、Z. Malinowski

  DOI：10.1080/00397919908085788

  日期：1999.2

  Abstract The synthesis of phthalazin-1-ones 6, 7, 8 via the reaction of 3-hydroxyisoindolin-l-ones 3, 4, 5 with hydrazine hydrate is described. Starting compounds 3, 4, 5 were regiospecifically prepared upon the lithiation (n-BuLi) of the benzanilides 1 and subsequently the reaction of the dilithiated anilides 2 with methyl pyridinecarboxylates.

  摘要 描述了通过 3-羟基异吲哚啉-1-酮 3、4、5 与水合肼反应合成酞嗪-1-酮 6、7、8。起始化合物 3、4、5 在苯甲酰苯胺 1 的锂化 (n-BuLi) 和随后二锂化的苯胺 2 与吡啶羧酸甲酯反应后进行区域特异性制备。
• Synthesis of 1,2-dihydro-1-oxophthalazin-4-yl trifluoromethanesulfonate and its application in the synthesis of 4-(aryl/heteroaryl/alkynyl)phthalazin-1(2H)-one
  作者：Ganesh Raosaheb Dhage、Santosh Rangnath Deshmukh、Shankar Ramchandra Thopate

  DOI：10.1039/c5ra03390j

  日期：——

  The regioselective synthesis of 1,2-dihydro-1-oxophthalazin-4-yl trifluoromethanesulfonate (3a) has been reported. The reaction of Tf2O (2a) with phthalhydrazide (1a) provides a rapid access to 3a with an excellent yield and a high level of regioselectivity. The synthetic utility of this triflate is further enhanced by carrying out the successful Suzuki and Sonogashira coupling reactions for the first

  已经报道了1，2-二氢-1-氧代酞嗪-4-基三氟甲磺酸盐（3a）的区域选择性合成。Tf 2 O（2a）与邻苯二甲酰肼（1a）的反应可快速获得3a，并具有优异的收率和较高的区域选择性。通过在3a上首次成功进行Suzuki和Sonogashira偶联反应，可进一步提高该三氟甲磺酸酯的合成效用，从而以高收率轻松获得一系列生物学上重要的4-芳基/杂芳基/炔基邻苯二氮酮。
• Pharmaceutical pyridine derivatives, processes for preparing the same and intermediates therefor
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP0848000A1

  公开（公告）日：1998-06-17

  A pyridine derivative of the formula (I): wherein A is group of the following formulae: R1 and R2 are each H, or protected or unprotected OH, R31, R41 and R42 are protected or unprotected hydroxymethyl, R32 is H, lower alkyl, or protected or unprotected hydroxymethyl, R33 is substituted or unsubstituted lower alkyl, and the dotted line means the presence or absence of a double bond' R5 and R6 are H, or protected or unprotected amino, or both combine together with the adjacent nitrogen to form substituted or unsubstituted heterocycle, or a pharmaceutically acceptable salt thereof, show excellent bronchoconstriction inhibitory activity and/or anti-inflammatory activity of airways, and are , useful in the prophylaxis or treatment of asthma.

  式（I）的吡啶衍生物： 其中 A 为下式中的基团： R1 和 R2 分别为 H，或受保护或未受保护的 OH，R31、R41 和 R42 为受保护或未受保护的羟甲基，R32 为 H、低级烷基或受保护或未受保护的羟甲基，R33 为取代或未取代的低级烷基，虚线表示存在或不存在双键' R5 和 R6 为 H、或受保护或未受保护的氨基，或两者与相邻的氮结合在一起形成取代或未取代的杂环，或其药学上可接受的盐，显示出优异的支气管收缩抑制活性和/或气道抗炎活性，可用于预防或治疗哮喘。
• Novel, Potent, and Selective Phosphodiesterase-4 Inhibitors as Antiasthmatic Agents:  Synthesis and Biological Activities of a Series of 1-Pyridylnaphthalene Derivatives
  作者：Tatsuzo Ukita、Masakatsu Sugahara、Yoshihiro Terakawa、Tooru Kuroda、Kazuteru Wada、Aya Nakata、Yasushi Ohmachi、Hideo Kikkawa、Katsuo Ikezawa、Kazuaki Naito

  DOI：10.1021/jm980314l

  日期：1999.3.1

  The structural requirements for potent and selective PDE4 inhibition were revealed in a 1-pyridylnaphthalene series, and the best compound (3kg, T-2585 . HCl) was chosen for further biological evaluation (PDE4 inhibition IC50 = 0.13 nM, selectivity PDE3/4 ratio = 14 000). Compound 3kg showed potent antispasmogenic activities (ED50 = 0.063 mg/kg for reduction of antigen-induced bronchoconstriction, intravenously; ED50 = 0.033 mg/kg for reduction of histamine-induced bronchoconstriction, intraduodenally) in guinea pigs with little cardiovascular effects. Furthermore, 3kg induced significantly weaker emetic effects than RP73401 after oral administration in ferrets and intravenous administration in dogs (3kg, none of 4 ferrets vomited at a dose of 10 mg/kg, po and none of 8 dogs vomited at; a dose of 0.3 mg/kg, iv; RP73401, 4 of 8 ferrets vomited at a dose of 3 mg/kg, po and 6 of 8 dogs vomited at a dose of 0.3 mg/kg, iv); that is compatible with the lower affinity for the high-affinity rolipram binding site (3kg, 2.6 nM; RP73401, 0.85 nM). This may imply that 3kg has an improved therapeutic ratio because of a broad margin between the K-i value of binding affinity and the IC50 value of PDE4 inhibition (ratio = 0.050).