6-Hydroxy-2-(pyridin-2-yl)-5-(2,4,6-trifluorophenyl)pyrimidin-4(3H)-one | 585535-50-8

• 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-Hydroxy-2-(pyridin-2-yl)-5-(2,4,6-trifluorophenyl)pyrimidin-4(3H)-one
• 英文别名: 4-hydroxy-2-pyridin-2-yl-5-(2,4,6-trifluorophenyl)-1H-pyrimidin-6-one
• CAS: 585535-50-8
• 化学式: C₁₅H₈F₃N₃O₂
• 分子量: 319.243
• InChiKey: HTMXGSLRAWGSPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  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：
  0.0
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-Hydroxy-2-(pyridin-2-yl)-5-(2,4,6-trifluorophenyl)pyrimidin-4(3H)-one 在 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 6-chloro-2-(pyridin-2-yl)-N-(2,2,2-trifluoroethyl)-5-(2,4,6-trifluorophenyl)pyrimidin-4-amine
  参考文献：
  名称：

  Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies

  摘要：

  Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer's disease (AD) and related tauopathies. However, thus far epothilone D has been the only brain-penetrant MT-stabilizer to be evaluated in tau transgenic mice and in AD patients. Furthermore, this natural product exhibits potential deficiencies as a drug candidate, including an intravenous route of administration and the inhibition of the P-glycoprotein (Pgp) transporter. Thus, the identification of alternative CNS-active MT-stabilizing agents that lack these potential limitations is of interest. Toward this objective, we have evaluated representative compounds from known classes of non-naturally occurring MT-stabilizing small molecules. This led to the identification of selected triazolopyrimidines and phenylpyrimidines that are orally bioavailable and brain-penetrant without disruption of Pgp function. Pharmacodynamic studies confirmed that representative compounds from these series enhance MT-stabilization in the brains of wild-type mice. Thus, these classes of MT-stabilizers hold promise for the development of orally active, CNS-directed MT-stabilizing therapies.

  DOI：

  10.1021/jm5005623
• 作为产物：
  描述：

  2-脒基吡啶盐酸盐 在 三正丁胺 、 sodium hydroxide 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 6-Hydroxy-2-(pyridin-2-yl)-5-(2,4,6-trifluorophenyl)pyrimidin-4(3H)-one
  参考文献：
  名称：

  Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies

  摘要：

  Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer's disease (AD) and related tauopathies. However, thus far epothilone D has been the only brain-penetrant MT-stabilizer to be evaluated in tau transgenic mice and in AD patients. Furthermore, this natural product exhibits potential deficiencies as a drug candidate, including an intravenous route of administration and the inhibition of the P-glycoprotein (Pgp) transporter. Thus, the identification of alternative CNS-active MT-stabilizing agents that lack these potential limitations is of interest. Toward this objective, we have evaluated representative compounds from known classes of non-naturally occurring MT-stabilizing small molecules. This led to the identification of selected triazolopyrimidines and phenylpyrimidines that are orally bioavailable and brain-penetrant without disruption of Pgp function. Pharmacodynamic studies confirmed that representative compounds from these series enhance MT-stabilization in the brains of wild-type mice. Thus, these classes of MT-stabilizers hold promise for the development of orally active, CNS-directed MT-stabilizing therapies.

  DOI：

  10.1021/jm5005623

文献信息

• Synthesis and SAR of 6-chloro-4-fluoroalkylamino-2-heteroaryl-5-(substituted)phenylpyrimidines as anti-cancer agents
  作者：Nan Zhang、Semiramis Ayral-Kaloustian、Thai Nguyen、Richard Hernandez、Judy Lucas、Carolyn Discafani、Carl Beyer

  DOI：10.1016/j.bmc.2008.11.016

  日期：2009.1

  ortho-position to the pyrimidyl core. The structure–activity relationship for the rest of the molecule in this 2-heteroarylpyrimidine series mimics that of the [1,2,4]triazolo[1,5-a]pyrimidine series. Like triazolopyrimidines and 2-cyanoaminopyrimidines, the 2-heteroarylpyrimidines retain the capability to overcome multidrug resistance due to Pgp. Mechanism of action studies showed that the lead compounds behaved

  描述了一系列的6-氯-4-氟烷基氨基-2-杂芳基-5-（取代）苯基嘧啶作为抗癌剂的合成和SAR。这一系列的2-杂芳基嘧啶是通过修饰我们先前报道的一系列抗肿瘤[1,2,4]三唑并[1,5- a ]嘧啶和2-氰基氨基嘧啶而开发的。对于2-杂芳基，当杂芳基在嘧啶基核的邻位具有氮原子时，可获得最佳活性。该2-杂芳基嘧啶系列中其余分子的结构-活性关系类似于[1,2,4]三唑[1,5- a ]的结构-活性关系]嘧啶系列。像三唑并嘧啶和2-氰基氨基嘧啶一样，2-杂芳基嘧啶保留克服由于Pgp引起的多药耐药性的能力。作用机理研究表明，先导化合物的行为与三唑并嘧啶和2-氰基氨基嘧啶相同。在体外和体内，该系列中的先导化合物比相应的三唑并嘧啶更有效。化合物21（PTI-868）在几种裸鼠异种移植模型中均显示出抑制肿瘤生长的作用，因此被选择进行临床前开发。
• 2- (2-pyridyl) -5-phenyl-6-aminopyrimidine, method and intermediate products for the production and use thereof for combating noxious fungi
  申请人：Schieweck Frank

  公开号：US20050107401A1

  公开（公告）日：2005-05-19

  The invention relates to 2-(2-pyridyl)-5-phenyl-6-amninopyrimidines of formula I, wherein the substitutes and the index have the following meaning: R 1 represents halogen, hydroxy, hyano, hxo, nitro, amino, mercapto, alkyl, halogenalkyl, alkenyl, alkinyl, cycloalkyl, alkoxy, halogenalkoxy, carboxyl, alkoxycarbonyl, carbamoyl, alkylaminocarbonyl, dialkylamincarbonyl, morpholinocarbonyl, pyrrolidinocarbonyl, alkylcarbonylamino, alkylamino. dialkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, hydroxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl; m=0 or 1-4; R 2 represents hydrogen, halogen, cyano, alkyl, halogenalkyl or alkoxy; R 3 , R 4 represents hydrogen, alkyl, halogenalkyl, cycloalkyl, halogencycloalkyl, alkenyl, halogenalkenyl, cycloalkenyl, alkinyl, halogenalkinyl or cycloalkinyl, R 3 and R 4 together with the nitrogen atom to which they are connected, form a five or six-membered ring which is interrupted by an atom from the group O, N or S and/or can be substituted according to the description; R 5 represents halogen, alkyl or halogenalkyl; R 6 represents hydrogen or one of the known groups in R 5 ; R 7 , R 8 represent hydrogen, halogen, alkyl or halogenalkyl; R 9 represents hydrogen, halogen, hydroxy, cyano, alkyl, alkoxy, cycloalkoxy, halogenalkoxy, alkoxycarbonyl or alkylaminocarbonyl. The invention also relates to a method and intermediate product for the production of said compound in addition to the use thereof for combating undesirable plants.

  本发明涉及式I的2-(2-吡啶基)-5-苯基-6-氨基嘧啶，其中取代基和索引具有以下含义：R1表示卤素、羟基、氰基、氢氧基、硝基、氨基、巯基、烷基、卤代烷基、烯基、炔基、环烷基、烷氧基、卤代烷氧基、羧基、烷氧羰基、氨基甲酰基、二烷基氨基甲酰基、吗啉基甲酰基、吡咯烷基甲酰基、烷基羰基氨基、烷基氨基、二烷基氨基、烷基硫基、烷基亚磺酰基、烷基磺酰基、羟基磺酰基、氨基磺酰基、烷基氨基磺酰基、二烷基氨基磺酰基；m=0或1-4；R2表示氢、卤素、氰基、烷基、卤代烷基或烷氧基；R3、R4表示氢、烷基、卤代烷基、环烷基、卤代环烷基、烯基、卤代烯基、环烯基、炔基、卤代炔基或环炔基，R3和R4与它们连接的氮原子一起形成一个由O、N或S组成的五元或六元环，该环被中断并且可以根据说明进行取代；R5表示卤素、烷基或卤代烷基；R6表示氢或R5中已知的一种基团；R7、R8表示氢、卤素、烷基或卤代烷基；R9表示氢、卤素、羟基、氰基、烷基、烷氧基、环烷氧基、卤代烷氧基、烷氧羰基或烷基氨基羰基。本发明还涉及一种制备所述化合物的方法和中间体以及用于防治不良植物的用途。
• 2-(2-pyridyl)-5-phenyl-6-aminopyrimidine, method and intermediate products for the production and use thereof for combating noxious fungi
  申请人：BASF Aktiengesellschaft

  公开号：US07320975B2

  公开（公告）日：2008-01-22

  The invention relates to 2-(2-pyridyl)-5-phenyl-6-aminopyrimidines of formula I, wherein the substitutes and the index have the following meaning: R1 represents halogen, hydroxy, hyano, hxo, nitro, amino, mercapto, alkyl, halogenalkyl, alkenyl, alkinyl, cycloalkyl, alkoxy, halogenalkoxy, carboxyl, alkoxycarbonyl, carbamoyl, alkylaminocarbonyl, dialkylamincarbonyl, morpholinocarbonyl, pyrrolidinocarbonyl, alkylcarbonylamino, alkylamino. dialkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, hydroxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl; m=0 or 1-4; R2 represents hydrogen, halogen, cyano, alkyl, halogenalkyl or alkoxy; R3, R4 represents hydrogen, alkyl, halogenalkyl, cycloalkyl, halogencycloalkyl, alkenyl, halogenalkenyl, cycloalkenyl, alkinyl, halogenalkinyl or cycloalkinyl, R3 and R4 together with the nitrogen atom to which they are connected, form a five or six-membered ring which is interrupted by an atom from the group O, N or S and/or can be substituted according to the description; R5 represents halogen, alkyl or halogenalkyl; R6 represents hydrogen or one of the known groups in R5; R7, R8 represent hydrogen, halogen, alkyl or halogenalkyl; R9 represents hydrogen, halogen, hydroxy, cyano, alkyl, alkoxy, cycloalkoxy, halogenalkoxy, alkoxycarbonyl or alkylaminocarbonyl. The invention also relates to a method and intermediate product for the production of said compound in addition to the use thereof for combating undesirable plants

  本发明涉及式I的2-(2-吡啶基)-5-苯基-6-氨基嘧啶，其中置换基和指数具有以下含义：R1代表卤素，羟基，氰基，氧化亚氮基，硝基，氨基，巯基，烷基，卤代烷基，烯基，炔基，环烷基，烷氧基，卤代烷氧基，羧基，烷氧羰基，氨基甲酰基，烷基氨基羰基，二烷基氨基羰基，吗啉氨基羰基，吡咯烷氨基羰基，烷基羰基氨基，烷基氨基，二烷基氨基，烷硫基，烷基亚砜基，烷基磺酰基，羟基磺酰基，氨基磺酰基，烷基氨基磺酰基，二烷基氨基磺酰基；m=0或1-4；R2代表氢，卤素，氰基，烷基，卤代烷基或烷氧基；R3，R4代表氢，烷基，卤代烷基，环烷基，卤代环烷基，烯基，卤代烯基，环烯基，炔基，卤代炔基或环炔基，R3和R4与它们连接的氮原子一起形成一个被O，N或S组的原子所打断的五元或六元环，并且可以根据说明进行取代；R5代表卤素，烷基或卤代烷基；R6代表氢或R5中已知的一种基团；R7，R8代表氢，卤素，烷基或卤代烷基；R9代表氢，卤素，羟基，氰基，烷基，烷氧基，环烷氧基，卤代烷氧基，烷氧羰基或烷基氨基羰基。本发明还涉及制备该化合物的方法和中间体以及用于防治不良植物的其应用。
• HETEROCYCLIC COMPOUNDS AND THEIR USE FOR THE TREATMENT OF NEURODEGENERATIVE TAUOPATHIES
  申请人：THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

  公开号：US20150224105A1

  公开（公告）日：2015-08-13

  The present invention is directed to triazolopyrimidine, phenylpyrimidine, pyridopyridazine, and pyridotriazine compounds which are microtubule-stabilizing compounds and their use in the treatment of neurodegenerative disorders, in particular, tauopathies, such as for example, Alzheimer's disease, frontotemporal lobar degeneration, Pick's disease, progressive supranuclear palsy (PSP), and corticobasal degeneration. In addition, the compounds of the invention may be useful for other diseases where tau pathology is a comorbidity or where microtubule function is compromised, for example, schizophrenia, Parkinson's disease (PD), PD with dementia, Lewy body disease with dementia, and amyotrophic lateral sclerosis.

  本发明涉及三唑并嘧啶、苯基嘧啶、吡啶并吡嗪和吡啶并三嗪类化合物，它们是微管稳定剂化合物，以及它们在治疗神经退行性疾病中的应用，特别是tau病理学，例如阿尔茨海默病、额颞叶变性、皮克氏病、进展性上皮核瘤和皮质基底节变性。此外，本发明中的化合物也可能对其他tau病理学是共病或微管功能受损的疾病有用，例如精神分裂症、帕金森病（PD）、带有痴呆的PD、带有痴呆的Lewy体病和肌萎缩侧索硬化症。
• 2-(2-PYRIDYL)-5-PHENYL-6-AMINOPYRIMIDINE, VERFAHREN UND ZWISCHENPRODUKTE ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG ZUR BEKÄMPFUNG VON SCHADPILZEN
  申请人：BASF Aktiengesellschaft

  公开号：EP1504001A1

  公开（公告）日：2005-02-09