6,6-dimethyl-1,4,5,6-tetrahydropyrimidin-2-amine hydrobromide

• 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: 6,6-dimethyl-1,4,5,6-tetrahydropyrimidin-2-amine hydrobromide
• 英文别名: 4,4-dimethyl-1,4,5,6-tetrahydropyrimidin-2-amine hydrobromide；6,6-Dimethyl-1,4,5,6-tetrahydro-pyrimidin-2-ylamine hydrobromide；6,6-dimethyl-4,5-dihydro-1H-pyrimidin-2-amine;hydrobromide
• 化学式: BrH*C₆H₁₃N₃
• 分子量: 208.101
• InChiKey: YGIPWHRKWHXPMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.65
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  50.4
• 氢给体数：
  3
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6,6-dimethyl-1,4,5,6-tetrahydropyrimidin-2-amine hydrobromide 在 sodium methylate 、 caesium carbonate 、 戴斯-马丁氧化剂 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 29.5h， 生成 3-fluoro-8,8-dimethyl-2-((R)-3-methylmorpholin-4-yl)-9-(2-oxo-2-pyridin-2-ylethyl)-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  Discovery of (2S)-8-[(3R)-3-Methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: A Novel Potent and Selective Inhibitor of Vps34 for the Treatment of Solid Tumors

  摘要：

  Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this lipid kinase in cancer maintenance and progression. Herein, we report the discovery of a series of tetrahydropyrimidopyrimidinone derivatives. Starting with hit compound 1a, medicinal chemistry optimization led to compound 31. This molecule displays potent activity, an exquisite selectivity for Vps34 with excellent properties. The X-ray crystal structure of compound 31 in human Vps34 illustrates how the unique molecular features of the morpholine synthon bestows selectivity against class I PI3Ks. This molecule exhibits suitable in vivo mouse PK parameters and induces a sustained inhibition of Vps34 upon acute administration. Compound 31 constitutes an optimized Vps34 inhibitor that could be used to investigate human cancer biology.

  DOI：

  10.1021/jm5013352
• 作为产物：
  描述：

  N-(3-甲基-2-丁烯基)邻苯二甲酰亚胺 在 hydrazine hydrate 、 氢溴酸 、 sodium methylate 、 trifluoroborane diethyl ether 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 溶剂黄146 、 甲苯 为溶剂， 反应 30.0h， 生成 6,6-dimethyl-1,4,5,6-tetrahydropyrimidin-2-amine hydrobromide
  参考文献：
  名称：

  PYRIMIDINONE DERIVATIVES, PREPARATION THEREOF AND PHARMACEUTICAL USE THEREOF

  摘要：

  这项发明涉及公式(Ia)或(Ib)的新产品：这些产品以所有同分异构体和盐的形式作为药物，特别是作为抗癌药物。

  公开号：

  US20130289031A1

文献信息

• Substituted 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 7-pyrimidinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1h)one derivatives for neurodegenerative disorders
  申请人：——

  公开号：US20040266793A1

  公开（公告）日：2004-12-30

  The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein: X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom; y represents a bond, an ethenylene group, an ethynylene group, an oxygen atom, a sulphur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, a nitrogen atom being optionally; or a methylene group optionally substituted; R1 represents a pyrimidine group optionally substituted; R2 may represent a C 1-6 alkyl group optionally substituted by a C 6,10 aryloxy or a C 6,10 arylamino group; a C 3-6 cycloalkyl group, a C 1-4 alkylthio group, a C 1-4 alkoxy group, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; R3 and R4 represents each independently a hydrogen atom, C 1-6 alkyl group, a hydroxy group, a C 1- 4 alkoxy group or a halogen atom; R5 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom. 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 GSK3&bgr;3 or GSK3&bgr;3 and cdk5/p25, such as Alzheimer disease. 1

  本发明涉及一种由式（I）表示的嘧啶酮衍生物或其盐，其中：X代表两个氢原子，硫原子，氧原子或C1-2烷基和氢原子；y代表键，乙烯基，乙炔基，氧原子，硫原子，磺酰基，亚磺酸基，羰基，氮原子（可选）或取代的亚甲基基团；R1表示可选取代的嘧啶基团；R2可以代表C1-6烷基，可选地被C6,10芳氧基或C6,10芳基氨基基团取代；C3-6环烷基，C1-4烷基硫基，C1-4烷氧基，C1-2全氟烷基，C1-3卤代烷基，苯硫基，苄基，苯环，茚环，5,6,7,8-四氢萘环，萘环，吡啶环，吡咯环，噻吩环，呋喃环或咪唑环；R3和R4各自独立地表示氢原子，C1-6烷基，羟基，C1-4烷氧基或卤素原子；R5表示氢原子，C1-6烷基或卤素原子。本发明还涉及一种药物，其中包括所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β3或GSK3β3和cdk5/p25的异常活性引起的神经退行性疾病，例如阿尔茨海默病。
• Substituted 2-pyridinyl-6,7,8,9-tetrahydropyrimido{1,2-a}pyrimidin-4-one and 7-pyridinyl-2,3-dihydroimidazo{1,2-a}pyrimidin-5(1h)one derivatives
  申请人：Gallet Thierry

  公开号：US20050049261A1

  公开（公告）日：2005-03-03

  The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein X represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom; Y represents a bond, an ethenylene group, an ethynylene group an oxygen atom, a sulfur atom, a sulfonyl group, a sulfoxide group, a carbonyl group, a hydroxyiminomethylene group, a dioxolan group, a nitrogen atom being optionally substituted; or a methylene group optionally substituted; or a methylene group optionally substituted; R1 represents a 2, 3 or 4-pyridine ring optionally substituted; R2 may represent a C 1-6 alkyl group optionally; a C 3-6 cycloalkyl group, a C 1-4 alkythio group, a C 1-4 alkoxy group, a C 1-2 perhalogenated alkyl group, a C 1-3 halogenated alkyl group, a phenylthio group, a benzyl group, a benzene ring, an indan ring, a 5,6,7,8-tetrahydronaphthalene ring, a naphthalene ring, a pyridine ring, a pyrrole ring, a thiophene ring, a furan ring or an imidazole ring; R3 and R4 represent, each independently, a hydrogen atom, a C 1-6 alkyl group, a hydroxy group, a C 1-4 alkoxy group or a halogen atom; R5 represents a hydrogen atom, a C 1-6 alkyl group or a halogen atom; with the proviso that when R3 and R4 represent each a hydrogen atom then R5 is not a hydrogen atom. 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 or GSK3β, and cdk5/p25, such as Alzheimer disease.

  本发明涉及一种由式(I)表示的嘧啶酮衍生物或其盐，其中X代表两个氢原子，硫原子，氧原子或C1-2烷基基团和一个氢原子；Y代表键，乙烯基团，乙炔基团，氧原子，硫原子，磺酰基，亚磺酸基，羰基，羟亚胺亚甲基基团，二氧杂环己烷基团，氮原子可选地取代；或取代的亚甲基基团；R1表示可选地取代的2、3或4-吡啶环；R2可以表示可选的C1-6烷基基团；C3-6环烷基团，C1-4烷硫基团，C1-4烷氧基团，C1-2全氟烷基团，C1-3卤代烷基团，苯硫基团，苯甲基基团，苯环，茚环，5,6,7,8-四氢萘环，萘环，吡啶环，吡咯环，噻吩环，呋喃环或咪唑环；R3和R4分别表示氢原子，C1-6烷基基团，羟基，C1-4烷氧基团或卤素原子；R5表示氢原子，C1-6烷基基团或卤素原子；但是当R3和R4分别表示氢原子时，R5不是氢原子。本发明还涉及一种药物，其包含所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β或GSK3β和cdk5/p25的异常活动引起的神经退行性疾病，如阿尔茨海默病。
• Heteroaryl substituted 2-pyridinyl and 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one derivatives
  申请人：Lochead Alistair

  公开号：US20050222172A1

  公开（公告）日：2005-10-06

  The invention relates to a pyrimidone derivative represented by formula (I) or a salt thereof wherein: (1) X represents two hydrogen atoms, a sulphur atom, an oxygen atom or a C 1-2 alkyl group and a hydrogen atom; Y represents a bond, an ethenylene group, an ethynylene group or a methylene group optionally substituted; R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring optionally substituted; R2 represents a heterocyclic bicyclic rings, having 1-4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom and having 5-9 carbon atoms, of formula (II) R3 represents a hydrogen atom, a C 1-6 alkyl group, a hydroxy group, a C 1-4 alkoxy group or a halogen atom; R4 represents a hydrogen atom, a C 1-6 alkyl group, a C 1-4 alkoxy group or a halogen atom. 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 or GSK3β and cdk5/p25, such as Alzheimer disease.

  本发明涉及一种由式（I）表示的嘧啶酮衍生物或其盐，其中：（1）X代表两个氢原子、一个硫原子、一个氧原子或一个C1-2烷基和一个氢原子；Y代表一种键合、一个乙烯基、一个乙炔基或一个甲基烷基，可选地取代；R1代表一个2、3或4-吡啶环或一个2、4或5-嘧啶环，可选地取代；R2代表一种杂环双环环，具有1-4个从氧原子、硫原子和氮原子中选择的杂原子，并具有5-9个碳原子，其式为（II）R3代表氢原子、C1-6烷基、羟基、C1-4烷氧基或卤素原子；R4代表氢原子、C1-6烷基、C1-4烷氧基或卤素原子。本发明还涉及一种药物，其包括所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β或GSK3β和cdk5/p25的异常活性引起的神经退行性疾病，例如阿尔茨海默病。
• HETEROARYL SUBSTITUTED 2-PYRIDINYL AND 2-PYRIMIDINYL -6,7,8,9-TETRAHYDROPYRIMIDO[1,2-a] PYRIMIDIN-4-ONE DERIVATIVES
  申请人：LOCHEAD Alistair

  公开号：US20070225300A1

  公开（公告）日：2007-09-27

  The invention relates to use of a pyrimidone derivative represented by formula (I) or a salt thereof wherein: X, Y, R1, R2, R3, R4, R5, m, n and p are as defined herein. In particular, the invention relates 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 or GSK3β and cdk5/p25, such as Alzheimer disease.

  本发明涉及使用由式（I）表示的嘧啶酮衍生物或其盐，其中：X，Y，R1，R2，R3，R4，R5，m，n和p如本文所定义。具体而言，本发明涉及一种药物，其包含所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β或GSK3β和cdk5/p25的异常活性引起的神经退行性疾病，如阿尔茨海默病。
• USE OF SUBSTITUTED 2-PYRIDINYL-6,7,8,9-TETRAHYDROPYRIMIDO[1,2-a] PYRIMIDIN-4-ONE AND 7-PYRIDINYL-2,3-DIHYDROIMIDAZO[1,2-a] PYRIMIDIN-5(1H)ONE DERIVATIVES AS THERAPEUTIC AGENTS
  申请人：GALLET Thierry

  公开号：US20070167461A1

  公开（公告）日：2007-07-19

  The invention relates to an use of pyrimidone derivative represented by formula (I) or a salt thereof: wherein m, n, p, X, Y, R1, R2, R3, R4 and R5 are as defined herein for treating a variety of disease states. More specifically, the invention relates 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 or GSK3β and cdk5/p25, such as Alzheimer's disease.

  本发明涉及使用由式(I)或其盐所表示的嘧啶酮衍生物的用途：其中m，n，p，X，Y，R1，R2，R3，R4和R5如本文所定义的，用于治疗各种疾病状态。更具体地，本发明涉及一种药物，其包括所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β或GSK3β和cdk5/p25的异常活动引起的神经退行性疾病，例如阿尔茨海默病。