1-(2-phenyl-pyrimidin-5-yl)-ethanone | 1071323-12-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2-phenyl-pyrimidin-5-yl)-ethanone
• 英文别名: 1-(2-Phenylpyrimidin-5-yl)ethanone
• CAS: 1071323-12-0
• 化学式: C₁₂H₁₀N₂O
• 分子量: 198.224
• InChiKey: JHGXKFWTQYONAL-UHFFFAOYSA-N

物化性质

• 沸点：
  254.9±23.0 °C(Predicted)
• 密度：
  1.147±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  42.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-phenyl-pyrimidin-5-yl)-ethanone 在 tetra-N-butylammonium tribromide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 2-phenyl-5-(2-phenyl-1H-imidazol-5-yl)pyrimidine
  参考文献：
  名称：

  新型酰胺和咪唑化合物作为有效的造血前列腺素D 2合酶抑制剂

  摘要：

  在寻找新颖且有效的小分子造血前列腺素D 2合酶（H-PGDS）抑制剂作为PGD 2介导的疾病和病症的潜在疗法时，我们探索了一系列包括多个以线性排列方式连接的芳基/杂芳基环的化合物。每种化合物在嘧啶或吡啶的“核”环与“尾”环系统之间都掺入了酰胺或咪唑“连接基”。我们通过荧光偏振结合测定，热位移测定，谷胱甘肽S-转移酶抑制测定和基于细胞的测定LPS诱导的PGD 2抑制的测定合成和筛选了二十个类似物。刺激。酰胺类似物在存在谷胱甘肽（GSH）的情况下，在热位移测定中显示的位移是在没有GSH的情况下进行的相同测定的十倍。咪唑类似物在两种测定条件之间没有产生明显的热位移变化，表明合成酶-GSH-抑制剂复合物中酰胺连接基可能具有稳定作用。咪唑模23，（KMN-010034）表明横跨优越效力的体外测定和良好的体外在人和豚鼠肝脏微粒体代谢稳定性。

  DOI：

  10.1016/j.bmcl.2020.127759
• 作为产物：
  描述：

  2-苯基嘧啶-5-甲酸 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1-(2-phenyl-pyrimidin-5-yl)-ethanone
  参考文献：
  名称：

  新型酰胺和咪唑化合物作为有效的造血前列腺素D 2合酶抑制剂

  摘要：

  在寻找新颖且有效的小分子造血前列腺素D 2合酶（H-PGDS）抑制剂作为PGD 2介导的疾病和病症的潜在疗法时，我们探索了一系列包括多个以线性排列方式连接的芳基/杂芳基环的化合物。每种化合物在嘧啶或吡啶的“核”环与“尾”环系统之间都掺入了酰胺或咪唑“连接基”。我们通过荧光偏振结合测定，热位移测定，谷胱甘肽S-转移酶抑制测定和基于细胞的测定LPS诱导的PGD 2抑制的测定合成和筛选了二十个类似物。刺激。酰胺类似物在存在谷胱甘肽（GSH）的情况下，在热位移测定中显示的位移是在没有GSH的情况下进行的相同测定的十倍。咪唑类似物在两种测定条件之间没有产生明显的热位移变化，表明合成酶-GSH-抑制剂复合物中酰胺连接基可能具有稳定作用。咪唑模23，（KMN-010034）表明横跨优越效力的体外测定和良好的体外在人和豚鼠肝脏微粒体代谢稳定性。

  DOI：

  10.1016/j.bmcl.2020.127759

文献信息

• MULTIHETEROARYL COMPOUNDS AS INHIBITORS OF H-PGDS AND THEIR USE FOR TREATING PROSTAGLANDIN D2 MEDIATED DISEASES
  申请人：Endres Gregory W.

  公开号：US20100075990A1

  公开（公告）日：2010-03-25

  Multiheteroaryl compounds, their preparation, pharmaceutical compositions comprising these compounds, and their pharmaceutical use in the prevention and treatment of prostaglandin D 2 mediated diseases and conditions that may be modulated by the inhibition of hematopoietic prostaglandin D synthase (H-PGDS).

  多杂环芳基化合物，它们的制备，包括这些化合物的药物组合物，以及它们在预防和治疗可能通过抑制造血前列腺素D合成酶（H-PGDS）调节的前列腺素D2介导的疾病和症状中的药用。
• Heterocyclic and Cyclic Analogs of Propargyl-Linked Inhibitors of Dihydrofolate Reductase
  申请人：Wright Dennis L.

  公开号：US20150225353A1

  公开（公告）日：2015-08-13

  Compounds of Formula I and Formula IA are inhibitors of dihydrofolate reductase and are suitable for use in compositions and methods for dihydrofolate reductase inhibition or, more specifically, treatment of a fungal infection, a bacterial infection or a protozoal infection, and, in specific embodiments, treatment of a fungal infection caused by C. albicans or C. glabrata : wherein R, R 1 , R 2 , R 3 , R 4 , A, B, E, V, W, X, Y and Z are as defined herein.

  式I和式IA的化合物是二氢叶酸还原酶的抑制剂，适用于二氢叶酸还原酶抑制或更具体地说，治疗真菌感染、细菌感染或原虫感染的组合物和方法，特定情况下，治疗由C. albicans或C. glabrata引起的真菌感染：其中R、R1、R2、R3、R4、A、B、E、V、W、X、Y和Z如本文所定义。
• Multiheteroaryl compounds as inhibitors of H-PGDS and their use for treating prostaglandin D2 mediated diseases
  申请人：Endres Gregory W.

  公开号：US08536185B2

  公开（公告）日：2013-09-17

  Multiheteroaryl compounds, their preparation, pharmaceutical compositions comprising these compounds, and their pharmaceutical use in the prevention and treatment of prostaglandin D2 mediated diseases and conditions that may be modulated by the inhibition of hematopoietic prostaglandin D synthase (H-PGDS).

  多取代杂环芳基化合物、其制备方法、包含这些化合物的制药组合物以及它们在预防和治疗可能通过抑制造血前列腺素D合酶（H-PGDS）调节的前列腺素D2介导的疾病和病况中的制药用途。
• Heterocyclic and cyclic analogs of propargyl-linked inhibitors of dihydrofolate reductase
  申请人：Wright Dennis L

  公开号：US09382213B2

  公开（公告）日：2016-07-05

  Compounds of Formula I and Formula IA are inhibitors of dihydrofolate reductase and are suitable for use in compositions and methods for dihydrofolate reductase inhibition or, more specifically, treatment of a fungal infection, a bacterial infection or a protozoal infection, and, in specific embodiments, treatment of a fungal infection caused by C. albicans or C. glabrata: wherein R, R1, R2, R3, R4, A, B, E, V, W, X, Y and Z are as defined herein.

  式I和式IA的化合物是二氢叶酸还原酶的抑制剂，适用于用于二氢叶酸还原酶抑制的组合物和方法，更具体地说，用于治疗真菌感染、细菌感染或原虫感染，特别是用于治疗由C. albicans或C. glabrata引起的真菌感染的组合物和方法，其中R、R1、R2、R3、R4、A、B、E、V、W、X、Y和Z的定义如本文所述。
• Propargyl-Linked Antifolates are Dual Inhibitors of <i>Candida albicans</i> and <i>Candida glabrata</i>
  作者：Narendran G-Dayanandan、Janet L. Paulsen、Kishore Viswanathan、Santosh Keshipeddy、Michael N. Lombardo、Wangda Zhou、Kristen M. Lamb、Adrienne E. Sochia、Jeremy B. Alverson、Nigel D. Priestley、Dennis L. Wright、Amy C. Anderson

  DOI：10.1021/jm401916j

  日期：2014.3.27

  Species of Candida, primarily C. albicans and with increasing prevalence, C. glabrata, are responsible for the majority of fungal bloodstream infections that cause morbidity, especially among immune compromised patients. While the development of new antifungal agents that target the essential enzyme, dihydrofolate reductase (DHFR), in both Candida species would be ideal, previous attempts have resulted in antifolates that exhibit inconsistencies between enzyme inhibition and antifungal properties. In this article, we describe the evaluation of pairs of propargyl-linked antifolates that possess similar physicochemical properties but different shapes. All of these compounds are effective at inhibiting the fungal enzymes and the growth of C. glabrata; however, the inhibition of the growth of C. albicans is shape-dependent with extended para-linked compounds proving more effective than compact, meta-linked compounds. Using crystal structures of DHFR from C. albicans and C. glabrata bound to lead compounds, 13 new para-linked compounds designed to inhibit both species were synthesized. Eight of these compounds potently inhibit the growth of both fungal species with three compounds displaying dual MIC values less than 1 mu g/mL. Analysis of the active compounds shows that shape and distribution of polar functionality is critical in achieving dual antifungal activity.