2,3-二氢-3-甲基-6-(4-吡啶)-2-硫氧代-4(1H)-嘧啶酮 | 521969-43-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2,3-二氢-3-甲基-6-(4-吡啶)-2-硫氧代-4(1H)-嘧啶酮
• 英文名称: 2-mercapto-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one
• 英文别名: 2-mercapto-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one；2-mercapto-3-methyl-6-(pyridin-4-yl)pyrimidin-4(3H)-one；3-methyl-6-pyridin-4-yl-2-sulfanylidene-1H-pyrimidin-4-one
• CAS: 521969-43-7
• 化学式: C₁₀H₉N₃OS
• 分子量: 219.267
• InChiKey: MXLBEFRKZYPNQP-UHFFFAOYSA-N

物化性质

• 沸点：
  376.2±52.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  77.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3-二氢-3-甲基-6-(4-吡啶)-2-硫氧代-4(1H)-嘧啶酮 在 phosphorous oxychloride 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 5.42h， 生成 2-[5-(2,6-dimethoxyphenyl)-3,6-dihydro-2H-pyridin-1-yl]-3-methyl-6-pyrimidin-4-yl-3H-pyrimidin-4-one
  参考文献：
  名称：

  [EN] 3-SUBSTITUTED-4-PYRIMIDONE DERIVATIVES
  [FR] DERIVES 4-PYRIMIDONES SUBSTITUES EN 3

  摘要：

  由以下公式（I）表示的嘧啶酮衍生物或其盐，或其溶剂合物或水合物，可用作tau蛋白激酶1抑制剂：其中X代表CH或氮原子；R1代表一个C?1#191-C?12#191烷基基团，可以被取代；R2代表一个C?1#191-C?8#191烷基基团，可以被取代，一个可以被取代的苯环，一个可以被取代的萘环，一个可以被取代的茚环，一个可以被取代的四氢萘环，或一个可选择地取代的杂环，其中有1到4个异原子，选择自氧原子、硫原子和氮原子，并且总共有5到10个组成环的原子。

  公开号：

  WO2004055007A1
• 作为产物：
  描述：

  异烟酸酰氯 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 magnesium chloride 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 21.0h， 生成 2,3-二氢-3-甲基-6-(4-吡啶)-2-硫氧代-4(1H)-嘧啶酮
  参考文献：
  名称：

  嘧啶酮类化合物或其可药用的盐、制备方法及 用途

  摘要：

  本发明公开了具有通式I所示结构的嘧啶酮类化合物或其可药用的盐、制备方法及用途。本发明将他克林片段和嘧啶酮结构融合在一个分子骨架内，首次实现了该类骨架结构在多靶点抗AD策略中的应用。通过药理实验可见，本发明嘧啶酮类化合物对于AChE/GSK‑3β双靶点具有明显的抑制作用。

  公开号：

  CN111349085B

文献信息

• [EN] 2, 3, 6-TRISUBSTITUTED-4-PYRIMIDONE DERIVATIVES<br/>[FR] DERIVES DE 2,3,6-TRISUBSTITUE 4-PYRIMIDONE
  申请人：MITSUBISHI PHARMA CORP

  公开号：WO2004085408A1

  公开（公告）日：2004-10-07

  A pyrimidone derivative having tau protein kinase 1 inhibitory activity which is represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof; useful for prventive and/or therapeutic treatment of diseass such as neurodegenerative diseases (e.g. Alzheimer disease); wherein Q represents CH or nitrogen atom; R represents a C1-C12 alkyl group; the ring of Formula (I): represents piperazine ring or piperidine ring; each X independently represents a C1-C8 alkyl group, an optionally partially hydrogenated C6-C10 aryl ring, an indan ring or the like; m represents an integer of 1 to 3; each Y independently represents a halogen atom, a hydroxy group, a cyano group, a C1-C6 alkyl group or the like; n represents an integer of 0 to 8; when X and Y or two Y groups are attached on the same carbon atom, they may combine to each other to form a C2-C6 alkylene group.

  一种具有tau蛋白激酶1抑制活性的嘧啶酮衍生物，其由化学式（I）或其盐、溶剂合物或水合物表示；用于预防和/或治疗神经退行性疾病（例如阿尔茨海默病）；其中Q代表CH或氮原子；R代表C1-C12烷基基团；化学式（I）的环：代表哌嗪环或哌啶环；每个X独立地代表C1-C8烷基基团、可选择性部分氢化的C6-C10芳环、茚环或类似物；m代表1到3的整数；每个Y独立地代表卤素原子、羟基、氰基、C1-C6烷基基团或类似物；n代表0到8的整数；当X和Y或两个Y基团连接在同一碳原子上时，它们可以结合形成C2-C6烷基基团。
• 2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; A new class of potent, selective and orally active glycogen synthase kinase-3β inhibitors
  作者：Kenji Fukunaga、Fumiaki Uehara、Keiichi Aritomo、Aya Shoda、Shinsuke Hiki、Masahiro Okuyama、Yoshihiro Usui、Kazutoshi Watanabe、Koichi Yamakoshi、Toshiyuki Kohara、Tokushi Hanano、Hiroshi Tanaka、Susumu Tsuchiya、Shinji Sunada、Ken-Ichi Saito、Jun-ichi Eguchi、Satoshi Yuki、Shoichi Asano、Shinji Tanaka、Akiko Mori、Keiji Yamagami、Hiroshi Baba、Takashi Horikawa、Masatake Fujimura

  DOI：10.1016/j.bmcl.2013.09.020

  日期：2013.12

  A series of 2-(2-phenylmorpholin-4-yl)pyrimidin-4(3H)-ones was synthesized and examined for their inhibitory activity against glycogen synthase kinase-3β (GSK-3β). We found 21, 29 and 30 to possess potent in vitro GSK-3β inhibitory activity with good in vitro PK profiles. 21 demonstrated significant decrease of tau phosphorylation after oral administration in mice and excellent PK profiles.

  合成了一系列2-（2-苯基吗啉-4-基）嘧啶-4（3 H）-酮，并检查了它们对糖原合酶激酶-3β（GSK-3β）的抑制活性。我们发现21，29和30，以在体外具有GSK-3β在体外PK性能良好的抑制活性有效。21显示在小鼠口服后tau磷酸化显着降低，PK表现出色。
• 3-Substituted-4-pyrimidone derivatives
  申请人：Uehara Fumiaki

  公开号：US20050090490A1

  公开（公告）日：2005-04-28

  a pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof having inhibitory activity against tau protein kinase 1: wherein R 1 represents a C 1 -C 12 alkyl group which may be substituted; R represents, for example, a group represented by the following formula (II): wherein R 2 and R 3 independently represent a hydrogen atom or a C 1 -C 8 alkyl group; R 4 represents a benzene ring which may be substituted, a naphthalene ring which may be substituted, an indan ring which may be substituted, a tetrahydronaphthalene ring which may be substituted, or an optionally substituted heterocyclic ring having 1 to 4 heteno atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, and having 5 to 10 ring-constituting atoms in total.

  一种以公式（I）表示的吡啶酮衍生物或其盐，或其溶剂或水合物，具有对tau蛋白激酶1的抑制活性：其中R1代表可以被取代的C1-C12烷基；R代表例如以下公式（II）所表示的基团：其中R2和R3独立地表示氢原子或C1-C8烷基；R4表示可以被取代的苯环，可以被取代的萘环，可以被取代的茚环，可以被取代的四氢萘环，或者是选择自氧原子、硫原子和氮原子组成的1至4个杂原子的可选取代杂环，总共具有5到10个构成环的原子。
• Substituted 2-(diaza-bicyclo-alkyl)-pyrimidone derivatives
  申请人：Lochead Alistair

  公开号：US20060025417A1

  公开（公告）日：2006-02-02

  The invention relates to a 2-(diaza-bicyclo-alkyl)-pyrimidone derivative represented by formula (I): wherein: R1 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom; R2 represents a hydrogen atom, a C 1-6 alkyl group optionally substituted by 1 to 4 substituents selected from a halogen atom, a hydroxyl group, a C 1-4 alkoxy group; a C 1-2 perhalogenated alkyl group, a benzyl group, a phenethyl group, a benzyloxycarbonyl group, a C 1-4 alkoxy carbonyl group, a benzene ring, a naphthalene ring, a quinoline ring, a phthalazine ring, a 5,6,7,8-tetrahydronaphthalene ring, a pyridine ring, an indole ring, a pyrrole ring, a thiophene ring, a benzenesulfonyl group, a benzoyl group, a pyridazine ring, a furan ring and an imidazole ring; each of the benzyl group, the phenethyl group, the benzyloxycarbonyl group, the benzenesulfonyl group, the benzoyl group and the benzene, naphthalene, quinoline, phthalazine, 5,6,7,8-tetrehydronaphthalene, pyridine, indole, pyrrole and thiophene rings being optionally substituted by 1 to 4 substituents selected from a C 1-6 alkyl group, a benzene ring, a halogen atom, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a hydroxyl group, a C 1-4 alkoxy group, a nitro group, a cyano group, an amino group, a C 1-6 monoalkylamino group and a C 2-10 dialkylamino group; R3 represents a 2, 4 or 5-pyrimidine ring or a 2, 3 or 4-pyridine ring, the rings being optionally substituted by a C 1-4 alkyl group, C 1-4 alkoxy group or a halogen atom; R4 represents a C 1-4 alkyl group optionally substituted by a hydroxyl group, a C 1-4 alkoxy group or a halogen atom and n represents 1 or 2; or a salt thereof, or a solvate thereof or a hydrate thereof. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β, such as Alzheimer's disease.

  本发明涉及一种2-(二氮杂双环烷基)-嘧啶酮衍生物，其化学式为(I)：其中：R1表示氢原子、C1-6烷基或卤素原子；R2表示氢原子、C1-6烷基（可选地被1至4个取自卤素原子、羟基、C1-4烷氧基、C1-2全卤代烷基、苄基、苯乙基、苄氧羰基、C1-4烷氧羰基、苯环、萘环、喹啉环、邻二氮杂菲环、5,6,7,8-四氢萘环、吡啶环、吲哚环、吡咯环、噻吩环、苯磺酰基、苯甲酰基、吡嗪环、呋喃环和咪唑环中的一种）；苄基、苯乙基、苄氧羰基、苯磺酰基、苯甲酰基和苯环、萘环、喹啉环、邻二氮杂菲环、5,6,7,8-四氢萘环、吡啶环、吲哚环、吡咯环、噻吩环中的每一种均可选择地被1至4个取自C1-6烷基、苯环、卤素原子、C1-2全卤代烷基、C1-3卤代烷基、羟基、C1-4烷氧基、硝基、氰基、氨基、C1-6单烷基氨基和C2-10双烷基氨基中的一种的取代基所取代；R3表示2、4或5-嘧啶环或2、3或4-吡啶环，环中可选择地被C1-4烷基、C1-4烷氧基或卤素原子取代；R4表示C1-4烷基（可选地被羟基、C1-4烷氧基或卤素原子取代）；n表示1或2；或其盐、溶剂或水合物。本发明还涉及一种药物，包括该衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β异常活性引起的神经退行性疾病，例如阿尔茨海默病。
• 2,3,6-Trisubstituted-4-pyrimidone derivatives
  申请人：Watanabe Kazutoshi

  公开号：US20060252768A1

  公开（公告）日：2006-11-09

  A pyrimidone derivative having tau protein kinase 1 inhibitory activity which is represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof; useful for prventive and/or therapeutic treatment of diseass such as neurodegenerative diseases (e.g. Alzheimer disease); wherein Q represents CH or nitrogen atom; R represents a C 1 -C 12 alkyl group; the ring of Formula (I): represents piperazine ring or piperidine ring; each X independently represents a C 1 -C 8 alkyl group, an optionally partially hydrogenated C 6 -C 10 aryl ring, an indan ring or the like; m represents an integer of 1 to 3; each independently represents a halogen atom, a hydroxy group, a cyano group, a C 1 -C 6 alkyl group or the like; n represents an integer of 0 to 8; when X and Y or two Y groups are attached on the same carbon atom, they may combine to each other to form a C 2 -C 6 alkylene group.

  具有tau蛋白激酶1抑制活性的嘧啶酮衍生物，其由式（I）或其盐、溶剂化物或水合物表示; 用于预防和/或治疗神经退行性疾病（例如阿尔茨海默病）等疾病; 其中Q表示CH或氮原子; R表示C1-C12烷基; 公式（I）的环表示哌嗪环或哌啶环; 每个X独立地表示C1-C8烷基，可选部分氢化的C6-C10芳环，茚环或类似物; m表示1至3的整数; 每个独立地表示卤素原子，羟基，氰基，C1-C6烷基或类似物; n表示0至8的整数; 当X和Y或两个Y基附着在同一碳原子上时，它们可以结合形成C2-C6烷基lene基团。