methyl thiazolo[5,4-c]pyridine-2-carboxylate | 1448536-69-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl thiazolo[5,4-c]pyridine-2-carboxylate
• 英文别名: Methyl thiazolo[5,4-c]pyridine-2-carboxylate；methyl [1,3]thiazolo[5,4-c]pyridine-2-carboxylate
• CAS: 1448536-69-3
• 化学式: C₈H₆N₂O₂S
• 分子量: 194.214
• InChiKey: ABEKCRYFOWJZAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  80.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl thiazolo[5,4-c]pyridine-2-carboxylate 、 (4-(苯基磺酰基)苯基)甲胺 在 三甲基铝 作用下， 以 甲苯 为溶剂， 反应 4.67h， 以48%的产率得到N-{[4-(benzenesulfonyl)phenyl]methyl}-[1,3]thiazolo[5,4-c]pyridine-2-carboxamide
  参考文献：
  名称：

  Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors

  摘要：

  Crystal structures of several urea- and thiourea-derived compounds in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein were utilized to design a potent amide-containing inhibitor bearing an aza-indole moiety (7, Nampt BC IC50 = 9.0 nM, A2780 cell proliferation IC50 = 10 nM). The Nampt-7 cocrystal structure was subsequently obtained and enabled the design of additional amide-containing inhibitors which incorporated various other fused 6,5-heterocyclic moieties and biaryl sulfone or sulfonamide motifs. Additional modifications of these molecules afforded many potent biaryl sulfone-containing Nampt inhibitors which also exhibited favorable in vitro ADME properties (microsomal and hepatocyte stability, MOCK permeability, plasma protein binding). An optimized compound (58) was a potent inhibitor of multiple cancer cell lines (IC50 <10 nM vs U251, HT1080, PC3, MiaPaCa2, and HCT116 lines), displayed acceptable mouse PK properties (F = 41%, CL = 52.4 mL/min/kg), and exhibited robust efficacy in a U251 mouse xenograft model.

  DOI：

  10.1021/jm4008664