N-(1-cyanomethylcarbamoylcyclohexyl)-4-(2-morpholin-4-ylthiazol-4-yl)benzamide

• 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: N-(1-cyanomethylcarbamoylcyclohexyl)-4-(2-morpholin-4-ylthiazol-4-yl)benzamide
• 英文别名: N-{1-[(cyanomethyl)carbamoyl]cyclohexyl}-4-[2-(morpholin-4-yl)-1,3-thiazol-4-yl]benzamide；N-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-(2-morpholin-4-yl-1,3-thiazol-4-yl)benzamide
• 化学式: C₂₃H₂₇N₅O₃S
• 分子量: 453.565
• InChiKey: TYJLGELUBBAGKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-乙酰基苯甲酸 在 溴 、 溶剂黄146 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 N-(1-cyanomethylcarbamoylcyclohexyl)-4-(2-morpholin-4-ylthiazol-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

文献信息

• Novel compounds and compositions as protease inhibitors
  申请人：AXYS PHARMACEUTICALS, INC.

  公开号：US20020086996A1

  公开（公告）日：2002-07-04

  The present invention relates to novel N-cyanomethyl amides which are cysteine protease inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.

  本发明涉及一种新颖的N-氰甲基酰胺，它们是半胱氨酸蛋白酶抑制剂，以及它们的药用盐和N-氧化物，它们作为治疗剂的用途以及它们的制备方法。
• N-CYANOMETHYLAMIDES AS PROTEASE INHIBITORS
  申请人：AXYS PHARMACEUTICALS, INC.

  公开号：EP1161415A2

  公开（公告）日：2001-12-12
• JP2002539192A
  申请人：——

  公开号：JP2002539192A

  公开（公告）日：2002-11-19
• US6476026B1
  申请人：——

  公开号：US6476026B1

  公开（公告）日：2002-11-05
• US6593327B2
  申请人：——

  公开号：US6593327B2

  公开（公告）日：2003-07-15