(4-methylpyridin-2-yl)carbamic acid phenyl ester | 939969-14-9

• 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: (4-methylpyridin-2-yl)carbamic acid phenyl ester
• 英文别名: phenyl (4-methylpyridin-2-yl)carbamate；Phenyl 4-methylpyridin-2-ylcarbamate；phenyl N-(4-methylpyridin-2-yl)carbamate
• CAS: 939969-14-9
• 化学式: C₁₃H₁₂N₂O₂
• 分子量: 228.25
• InChiKey: XUMMWZLQBOZEFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-((butylamino)methyl)benzoate 、 (4-methylpyridin-2-yl)carbamic acid phenyl ester 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以34%的产率得到methyl 4-[[1-butyl-3-(4-methylpyridin-2-yl)ureido]methyl]benzoate
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Selective Histone Deacetylase 6 Inhibitors in Melanoma Models

  摘要：

  Only a handful of therapies offer significant improvement in the overall survival in cases of melanoma, a cancer whose incidence has continued to rise in the past 30 years. In our effort to identify potent and isoform-selective histone deacetylase (HDAC) inhibitors as a therapeutic approach to melanoma, a series of new HDAC6 inhibitors based on the nexturastat A scaffold were prepared. The new analogues 4d, 4e, and 7b bearing added hydrophilic substituents, so as to establish additional hydrogen bonding on the rim of the HDAC6 catalytic pocket, exhibit improved potency against HDAC6 and retain selectivity over HDAC1. Compound 4d exhibits antiproliferative effects on several types of melanoma and lymphoma cells. Further studies indicates that 4d selectively increases acetylated tubulin levels in vitro and elicits an immune response through down-regulating cytokine IL-10. A preliminary in vivo efficacy study indicates that 4d possesses improved capability to inhibit melanoma tumor growth and that this effect is based on the regulation of inflammatory and immune responses.

  DOI：

  10.1021/acsmedchemlett.7b00223
• 作为产物：
  描述：

  2-氨基-4-甲基吡啶 、 氯甲酸苯酯 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (4-methylpyridin-2-yl)carbamic acid phenyl ester
  参考文献：
  名称：

  4-(3-Chloro-5-(trifluoromethyl)pyridin-2-yl)-N-(4-methoxypyridin-2-yl)piperazine-1-carbothioamide (ML267), a Potent Inhibitor of Bacterial Phosphopantetheinyl Transferase That Attenuates Secondary Metabolism and Thwarts Bacterial Growth

  摘要：

  4'-Phosphopantetheinyl transferases (PPTases) catalyze a post-translational modification essential to bacterial cell viability and virulence. We present the discovery and medicinal chemistry optimization of 2-pyridinyl-N-(4-aryl)-piperazine-1-carbothioamides, which exhibit submicromolar inhibition of bacterial Sfp-PPTase with no activity toward the human orthologue. Moreover, compounds within this class possess antibacterial activity in the absence of a rapid cytotoxic response in human cells. An advanced analogue of this series, ML267 (55), was found to attenuate production of an Sfp-PPTase-dependent metabolite when applied to Bacillus subtilis at sublethal doses. Additional testing revealed antibacterial activity against methicillin-resistant Staphylococcus aureus, and chemical genetic studies implicated efflux as a mechanism for resistance in Escherichia coli. Additionally, we highlight the in vitro absorption, distribution, metabolism; and excretion and in vivo pharmacokinetic profiles of compound 55 to further demonstrate the potential utility of this small-molecule inhibitor.

  DOI：

  10.1021/jm401752p