4-[2-[Methyl-(4-methylpiperazin-1-yl)amino]-1,3-thiazol-4-yl]benzoic acid | 871828-62-5

• 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-[2-[Methyl-(4-methylpiperazin-1-yl)amino]-1,3-thiazol-4-yl]benzoic acid
• CAS: 871828-62-5
• 化学式: C₁₆H₂₀N₄O₂S
• 分子量: 332.426
• InChiKey: GOQOWXWRCHPKQP-UHFFFAOYSA-N

物化性质

• 沸点：
  510.4±60.0 °C(predicted)
• 密度：
  1.316±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  88.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[2-[Methyl-(4-methylpiperazin-1-yl)amino]-1,3-thiazol-4-yl]benzoic acid 、 1-amino-N-(cyanomethyl)cyclohexanecarboxamide methanesulfonate 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-[2-[methyl-(4-methylpiperazin-1-yl)amino]-1,3-thiazol-4-yl]benzamide
  参考文献：
  名称：

  Design and Synthesis of Tri-Ring P₃ Benzamide-Containing Aminonitriles as Potent, Selective, Orally Effective Inhibitors of Cathepsin K

  摘要：

  We have prepared a series of achiral aminoacetonitriles, bearing tri-ring benzamide moieties and an aminocyclohexanecarboxylate residue at P-2. This combination of binding elements resulted in sub-250 pM, reversible, selective, and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of bovine bone). The best compound in this series, 39n (CRA-013783/ L-006235), was orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen breakdown products were reduced by up to 76% dose-dependently. Plasma concentrations of 39n above the bone resorption IC50 after 24 h indicated a correlation between functional cellular and in vivo assays. Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.

  DOI：

  10.1021/jm058198r
• 作为产物：
  描述：

  4-乙酰基苯甲酸 在 盐酸 、 sodium hydroxide 、 溴 、 sodium hydride 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.25h， 生成 4-[2-[Methyl-(4-methylpiperazin-1-yl)amino]-1,3-thiazol-4-yl]benzoic acid
  参考文献：
  名称：

  Design and Synthesis of Tri-Ring P₃ Benzamide-Containing Aminonitriles as Potent, Selective, Orally Effective Inhibitors of Cathepsin K

  摘要：

  We have prepared a series of achiral aminoacetonitriles, bearing tri-ring benzamide moieties and an aminocyclohexanecarboxylate residue at P-2. This combination of binding elements resulted in sub-250 pM, reversible, selective, and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of bovine bone). The best compound in this series, 39n (CRA-013783/ L-006235), was orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen breakdown products were reduced by up to 76% dose-dependently. Plasma concentrations of 39n above the bone resorption IC50 after 24 h indicated a correlation between functional cellular and in vivo assays. Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.

  DOI：

  10.1021/jm058198r