化合物L006235 | 294623-49-7

• 物质功能分类: 医药中间体 - 原料药中间体
• 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: 化合物L006235
• 中文别名: N-[1-[[[(氰基甲基)氨基]羰基]环己基]-4-[2-(4-甲基-1-哌嗪基)-4-噻唑基]苯甲酰胺
• 英文名称: CRA-03783
• 英文别名: N-(1-Cyanomethylcarbamoylcyclohexyl]-4-[2-(4-methylpiperazin-1-yl)thiazol-4-yl]benzamide；N-(1-((cyanomethyl)carbamoyl)cyclohexyl)-4-(2-(4-methylpiperazin-1-yl)thiazol-4-yl)benzamide；N-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-[2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]benzamide
• CAS: 294623-49-7
• 化学式: C₂₄H₃₀N₆O₂S
• 分子量: 466.607
• InChiKey: FIVYCSWOCXEWSE-UHFFFAOYSA-N

物化性质

• 密度：
  1.31±0.1 g/cm3(Predicted)
• 溶解度：
  <46.66mg/ml，溶于 DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  7

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

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 化合物L006235
  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
• USE OF CATHEPSIN K INHIBITION FOR THE TREATMENT AND/OR PROPHYLAXIS OF PULMONARY HYPERTENSION AND/OR HEART FAILURE
  申请人：Golz Stefan

  公开号：US20140155383A1

  公开（公告）日：2014-06-05

  The present invention relates to the use of cathepsin K and/or cathepsin S inhibitors in a method for the treatment and/or prophylaxis of pulmonary hypertension and/or heart failure.
• US6476026B1
  申请人：——

  公开号：US6476026B1

  公开（公告）日：2002-11-05