6-ethyl-5-[3-(6-phenyl-pyridin-3-yl)-but-1-ynyl]-pyrimidine-2,4-diamine | 1569902-04-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-ethyl-5-[3-(6-phenyl-pyridin-3-yl)-but-1-ynyl]-pyrimidine-2,4-diamine
• 英文别名: 6-Ethyl-5-[3-(6-phenyl-3-pyridyl)but-1-ynyl]pyrimidine-2,4-diamine；6-ethyl-5-[3-(6-phenylpyridin-3-yl)but-1-ynyl]pyrimidine-2,4-diamine
• CAS: 1569902-04-0
• 化学式: C₂₁H₂₁N₅
• 分子量: 343.431
• InChiKey: JKSKINFMKRSXHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  90.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(6-苯基吡啶-3-基)乙酮 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 6-ethyl-5-[3-(6-phenyl-pyridin-3-yl)-but-1-ynyl]-pyrimidine-2,4-diamine
  参考文献：
  名称：

  Heterocyclic and Cyclic Analogs of Propargyl-Linked Inhibitors of Dihydrofolate Reductase

  摘要：

  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。

  公开号：

  US20150225353A1

文献信息

• 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。
• US9382213B2
  申请人：——

  公开号：US9382213B2

  公开（公告）日：2016-07-05
• 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.