3-methoxy-4'-methyl-4-(1-methyl-prop-2-ynyl)biphenyl | 1569901-85-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-methoxy-4'-methyl-4-(1-methyl-prop-2-ynyl)biphenyl
• CAS: 1569901-85-4
• 化学式: C₁₈H₁₈O
• 分子量: 250.34
• InChiKey: HIAPCDAECSUZMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.41
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  9.23
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  3-methoxy-4'-methyl-4-(1-methyl-prop-2-ynyl)biphenyl 、 6-乙基-5-碘嘧啶-2,4-二胺 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以77%的产率得到6-ethyl-5-[3-(3-methoxy-4'-methylbiphenyl-4-yl)-but-1-ynyl]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Propargyl-Linked Antifolates are Dual Inhibitors of Candida albicans and Candida glabrata

  摘要：

  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.

  DOI：

  10.1021/jm401916j
• 作为产物：
  描述：

  4-溴-2-甲氧基苯乙酮 在 bis-triphenylphosphine-palladium(II) chloride 、 mercury(II) diacetate 、 potassium carbonate 、 caesium carbonate 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 10.08h， 生成 3-methoxy-4'-methyl-4-(1-methyl-prop-2-ynyl)biphenyl
  参考文献：
  名称：

  Propargyl-Linked Antifolates are Dual Inhibitors of Candida albicans and Candida glabrata

  摘要：

  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.

  DOI：

  10.1021/jm401916j