(4-methylpiperazin-1-yl)thiourea | 849682-31-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (4-methylpiperazin-1-yl)thiourea
• 英文别名: (4-Methylpiperazin-1-yl)thiourea
• CAS: 849682-31-1
• 化学式: C₆H₁₄N₄S
• 分子量: 174.27
• InChiKey: ZOPLRPTVJUJANI-UHFFFAOYSA-N

物化性质

• 沸点：
  268.6±50.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  76.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-methylpiperazin-1-yl)thiourea 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 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 4-[2-[(4-methylpiperazin-1-yl)amino]-1,3-thiazol-4-yl]-N-[1-[[(3S,4R)-2-oxo-4-phenoxyazetidin-3-yl]carbamoyl]cyclohexyl]benzamide
  参考文献：
  名称：

  3,4-Disubstituted azetidinones as selective inhibitors of the cysteine protease cathepsin K. Exploring P3 elements for potency and selectivity

  摘要：

  The synthesis of a series of highly potent and selective inhibitors of cathepsin K based on the 3,4-disubstituted azetidin-2-one warhead is reported. A high degree of potency and selectivity was achieved by introducing a basic nitrogen into the distal part of the P3 element of the molecule. Data from kinetic and mass spectrometry experiments are consistent with the interpretation that compounds of this series transiently acylate the sulfhydrile of cathepsin K. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.12.088
• 作为产物：
  描述：

  1-氨基-4-甲基哌嗪 在 ammonium hydroxide 、 TEA 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (4-methylpiperazin-1-yl)thiourea
  参考文献：
  名称：

  3,4-Disubstituted azetidinones as selective inhibitors of the cysteine protease cathepsin K. Exploring P3 elements for potency and selectivity

  摘要：

  The synthesis of a series of highly potent and selective inhibitors of cathepsin K based on the 3,4-disubstituted azetidin-2-one warhead is reported. A high degree of potency and selectivity was achieved by introducing a basic nitrogen into the distal part of the P3 element of the molecule. Data from kinetic and mass spectrometry experiments are consistent with the interpretation that compounds of this series transiently acylate the sulfhydrile of cathepsin K. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.12.088

文献信息

• Imaging probes
  申请人：WENDT Karl-Ulrich

  公开号：US20100189658A1

  公开（公告）日：2010-07-29

  The present invention relates to molecular probes of the formula (I) L1-R1-L} n -A-CO—NH—R2-L2  (I) as defined herein that allow for the observation of the catalytic activity of a selected cathepsin in in vitro assays, in cells or in multicellular organisms, a method for their preparation and the use thereof.

  本发明涉及分子探针的公式（I）L1-R1-L}n-A-CO—NH—R2-L2  （I），如本文所定义，允许在体外测定、细胞或多细胞生物中观察所选的蛋白酶的催化活性，以及它们的制备方法和使用方法。
• 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.
• IMAGING PROBES
  申请人：Sanofi-Aventis

  公开号：EP2117605A2

  公开（公告）日：2009-11-18
• US8771644B2
  申请人：——

  公开号：US8771644B2

  公开（公告）日：2014-07-08
• [EN] IMAGING PROBES<br/>[FR] SONDES D'IMAGERIE
  申请人：SANOFI AVENTIS

  公开号：WO2008104271A2

  公开（公告）日：2008-09-04

  [EN] The present invention relates to molecular probes of the formula (I) L1 -R1 -L}_n-A-CO-NH-R2-L2 (I) as defined herein that allow for the observation of the catalytic activity of a selected cathepsin in in vitro assays, in cells or in multicellular organisms, a method for their preparation and the use thereof.
  [FR] Sondes moléculaires de formule (I) L1 -R1 -L}_n-A-CO-NH-R2-L2 (I) telle que définie ici permettant l'observation de l'activité catalytique d'une cathepsine sélectionnée dans des dosages in vitro, dans des cellules ou des organismes multicellulaires; procédé associé à leur élaboration; et utilisation de celles-ci.