4-bromo-N-[1-(cyanomethylcarbamoyl)cyclohexyl]benzamide | 871828-07-8

• 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-bromo-N-[1-(cyanomethylcarbamoyl)cyclohexyl]benzamide
• CAS: 871828-07-8
• 化学式: C₁₆H₁₈BrN₃O₂
• 分子量: 364.242
• InChiKey: AGJGTOPQVLECER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  82
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-bromo-N-[1-(cyanomethylcarbamoyl)cyclohexyl]benzamide 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 1-[4-(trimethylsilanylethynyl)benzoylamino]cyclohexanecarboxylate
  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：

  1-(N-叔丁氧羰基氨基)环己烷甲酸 在 4-二甲氨基吡啶 、 甲烷磺酸 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-bromo-N-[1-(cyanomethylcarbamoyl)cyclohexyl]benzamide
  参考文献：
  名称：

  探索组织蛋白酶B S2口袋的荧光特性的新型组织蛋白酶抑制剂：设计，合成和生物学评估

  摘要：

  氟还是氟？基于β，β-二氟环脂族氨基酸，新的二肽腈文库被评估为人组织蛋白酶抑制剂。通过分子建模和NMR研究阐明了氟化面相对于组织蛋白酶B蛋白质结构的方向（见图）。对于（R）配置的体，氟原子被定向到S 2凹穴，而在（S）配置的dis体中，氟化面暴露在溶剂中。

  DOI：

  10.1002/chem.201100113

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.
• New Cathepsin Inhibitors to Explore the Fluorophilic Properties of the S ² Pocket of Cathepsin B: Design, Synthesis, and Biological Evaluation
  作者：Santos Fustero、Vanessa Rodrigo、María Sánchez‐Roselló、Carlos del Pozo、Joaquín Timoneda、Maxim Frizler、Mihiret T. Sisay、Jürgen Bajorath、Luis P. Calle、F. Javier Cañada、Jesús Jiménez‐Barbero、Michael Gütschow

  DOI：10.1002/chem.201100113

  日期：2011.5.2

  β‐difluorinated cycloaliphatic amino acids, a library of new dipeptide nitriles was evaluated as human cathepsin inhibitors. The orientation of the fluorinated face relative to the protein structure of cathepsin B was elucidated by molecular modeling and NMR studies (see figure). For (R)‐configured eutomers, the fluorine atoms are directed to the S2 pocket, whereas in (S)‐configured distomers, the fluorinated face

  氟还是氟？基于β，β-二氟环脂族氨基酸，新的二肽腈文库被评估为人组织蛋白酶抑制剂。通过分子建模和NMR研究阐明了氟化面相对于组织蛋白酶B蛋白质结构的方向（见图）。对于（R）配置的体，氟原子被定向到S 2凹穴，而在（S）配置的dis体中，氟化面暴露在溶剂中。