4-[2-(1,4-二甲基-哌啶-4-基)-噻唑-4-基]-苯甲酸 | 1027041-17-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-[2-(1,4-二甲基-哌啶-4-基)-噻唑-4-基]-苯甲酸
• 英文名称: 4-[2-(1,4-Dimethylpiperidin-4-yl)-1,3-thiazol-4-yl]benzoic acid
• CAS: 1027041-17-3
• 化学式: C₁₇H₂₀N₂O₂S
• 分子量: 316.424
• InChiKey: WHCRLJZNFVXXNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[2-(1,4-二甲基-哌啶-4-基)-噻唑-4-基]-苯甲酸 、 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， 反应 3.0h， 生成 N-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-[2-(1,4-dimethylpiperidin-4-yl)-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 溴 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 4-[2-(1,4-二甲基-哌啶-4-基)-噻唑-4-基]-苯甲酸
  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

文献信息

• Design and Synthesis of Tri-Ring P₃ Benzamide-Containing Aminonitriles as Potent, Selective, Orally Effective Inhibitors of Cathepsin K
  作者：James T. Palmer、Clifford Bryant、Dan-Xiong Wang、Dana E. Davis、Eduardo L. Setti、Robert M. Rydzewski、Shankar Venkatraman、Zong-Qiang Tian、Leland C. Burrill、Rohan V. Mendonca、Eric Springman、John McCarter、Tobee Chung、Harry Cheung、James W. Janc、Mary McGrath、John R. Somoza、Philip Enriquez、Z. Walter Yu、Robert M. Strickley、Liang Liu、Michael C. Venuti、M. David Percival、Jean-Pierre Falgueyret、Peppi Prasit、Renata Oballa、Denis Riendeau、Robert N. Young、Gregg Wesolowski、Sevgi B. Rodan、Colena Johnson、Donald B. Kimmel、Gideon Rodan

  DOI：10.1021/jm058198r

  日期：2005.12.1

  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.