2-(4-甲基-1-哌嗪)-硫代乙酰胺 | 164926-91-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 2-(4-甲基-1-哌嗪)-硫代乙酰胺
• 中文别名: 紫外线吸收剂-928
• 英文名称: 2-(1-methyl-4-piperazinyl)thioacetamide
• 英文别名: 2-(4-methylpiperazin-1-yl)ethanethioamide
• CAS: 164926-91-4
• 化学式: C₇H₁₅N₃S
• mdl: MFCD06738873
• 分子量: 173.282
• InChiKey: KAUKVYOVJQGSKW-UHFFFAOYSA-N

物化性质

• 沸点：
  277.0±50.0 °C(Predicted)
• 密度：
  1.119±0.06 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：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.857
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  2-(4-甲基-1-哌嗪)-硫代乙酰胺 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 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 N-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-[2-[(4-methylpiperazin-1-yl)methyl]-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：

  1-(4-甲基哌嗪)乙腈 在 硫化氢 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以35%的产率得到2-(4-甲基-1-哌嗪)-硫代乙酰胺
  参考文献：
  名称：

  Receptor-Type Kinase Modulators and Methods of Use

  摘要：

  本发明提供了用于调节受体激酶活性的化合物，特别是ephrin和EGFR，并利用这些化合物及其药物组合物治疗由受体激酶活性介导的疾病的方法。由受体激酶活性介导的疾病包括但不限于部分表现为细胞增殖异常水平（即肿瘤生长）、程序性细胞死亡（凋亡）、细胞迁移和侵袭以及与肿瘤生长相关的血管生成的疾病。本发明的化合物包括“谱选择性”激酶调节剂，这些化合物抑制、调节和/或调节跨受体型酪氨酸激酶亚家族的信号传导，包括ephrin和EGFR。

  公开号：

  US20160129032A1

文献信息

• [EN] RECEPTOR-TYPE KINASE MODULATORS AND METHODS OF USE<br/>[FR] MODULATEURS DE KINASE DE TYPE RECEPTEUR ET PROCEDES D'UTILISATION
  申请人：EXELIXIS INC

  公开号：WO2004006846A2

  公开（公告）日：2004-01-22

  The present invention provides compounds for modulating receptor kinase activity, particularly ephrin and EGFR, and methods of treating diseases mediated by receptor kinase activity utilizing the compounds and pharmaceutical compositions thereof. Diseases mediated by receptor kinase activity include, but are not limited to, diseases characterized in part by abnormal levels of cell proliferation (i.e. tumor growth), programmed cell death ( apoptosis), cell migration and invasion and angiogenesis associated with tumor growth. Compounds of the invention include 'spectrum selective' kinase modulators, compounds that inhibit, regulate and/or mo dulate signal transduction across subfamilies of receptor-type tyrosine kinases, including ephrin and EGFR.

  本发明提供了用于调节受体激酶活性的化合物，特别是调节ephrin和EGFR，以及利用这些化合物和其制剂治疗受受体激酶活性介导的疾病的方法。受受体激酶活性介导的疾病包括但不限于部分由细胞增殖异常水平（即肿瘤生长）、程序性细胞死亡（凋亡）、细胞迁移和侵袭以及与肿瘤生长相关的血管生成所特征化的疾病。本发明的化合物包括“光谱选择性”激酶调节剂，这些化合物抑制、调节和/或调节受体型酪氨酸激酶亚家族之间的信号转导，包括ephrin和EGFR。
• Receptor-type kinase modulators and methods of use
  申请人：Rice D Kenneth

  公开号：US20060069077A1

  公开（公告）日：2006-03-30

  The present invention provides compounds for modulating receptor kinase activity, particularly ephrin and EGFR, and methods of treating diseases mediated by receptor kinase activity utilizing the compounds and pharmaceutical compositions thereof. Diseases mediated by receptor kinase activity include, but are not limited to, diseases characterized in part by abnormal levels of cell proliferation (i.e. tumor growth), programmed cell death (apoptosis), cell migration and invasion and angiogenesis associated with tumor growth. Compounds of the invention include “spectrum selective” kinase modulators, compounds that inhibit, regulate and/or modulate signal transduction across subfamilies of receptor-type tyrosine kinases, including ephrin and EGFR.

  本发明提供了用于调节受体激酶活性的化合物，特别是调节ephrin和EGFR等受体激酶活性的化合物，并利用这些化合物和其制剂治疗由受体激酶活性介导的疾病的方法。由受体激酶活性介导的疾病包括但不限于部分表现为细胞增殖异常水平（即肿瘤生长）、程序性细胞死亡（凋亡）、细胞迁移和侵袭以及与肿瘤生长相关的血管生成的疾病。本发明的化合物包括“光谱选择性”激酶调节剂，可以抑制、调节和/或调节受体型酪氨酸激酶亚家族之间的信号转导，包括ephrin和EGFR。
• Processes for the preparation of substituted quinazolines
  申请人：Symphony Evolution, Inc.

  公开号：US09163006B2

  公开（公告）日：2015-10-20

  The present disclosure provides compounds for modulating receptor kinase activity, particularly ephrin and EGFR, and methods of treating diseases mediated by receptor kinase activity utilizing the compounds and pharmaceutical compositions thereof. The compounds are generally of formula (I): Diseases mediated by receptor kinase activity include, but are not limited to, diseases characterized in part by abnormal levels of cell proliferation (i.e. tumor growth), programmed cell death (apoptosis), cell migration and invasion and angiogenesis associated with tumor growth. Compounds of the invention include “spectrum selective” kinase modulators, compounds that inhibit, regulate and/or modulate signal transduction across subfamilies of receptor-type tyrosine kinases, including ephrin and EGFR. Also disclosed are methods of making compounds for formula 8: comprising introducing group E2 into a compound of formula 7: wherein Ar, Z, P, and E2 are defined herein.

  本公开提供用于调节受体激酶活性的化合物，特别是ephrin和EGFR，并利用这些化合物和其药物组合物治疗受受体激酶活性介导的疾病的方法。这些化合物通常具有式（I）：受受体激酶活性介导的疾病包括但不限于疾病的特征部分为细胞增殖异常（即肿瘤生长）、程序性细胞死亡（凋亡）、细胞迁移和侵袭以及与肿瘤生长相关的血管生成。本发明的化合物包括“光谱选择性”激酶调节剂，这些化合物抑制、调节和/或调节受体型酪氨酸激酶亚家族之间的信号转导，包括ephrin和EGFR。还公开了制备式8化合物的方法：包括将E2基团引入式7化合物中：其中Ar、Z、P和E2在此处定义。
• Process for preparing receptor-type kinase modulators
  申请人：Symphony Evolution, Inc.

  公开号：EP2280003A2

  公开（公告）日：2011-02-02

  The present invention provides a process for preparing compounds for modulating receptor kinase activity, particularly ephrin and EGFR. Diseases mediated by receptor kinase activity include, but are not limited to, diseases characterized in part by abnormal levels of cell proliferation (i.e. tumor growth), programmed cell death (apoptosis), cell migration and invasion and angiogenesis associated with tumor growth. Compounds provided by the process of the invention include "spectrum selective" kinase modulators, compounds that inhibit, regulate and/or modulate signal transduction across subfamilies of receptor-type tyrosine kinases, including ephrin and EGFR.

  本发明提供了一种用于制备调节受体激酶活性（尤其是表皮生长因子受体和表皮生长因子受体）的化合物的工艺。由受体激酶活性介导的疾病包括但不限于部分以异常水平的细胞增殖（即肿瘤生长）、程序性细胞死亡（凋亡）、细胞迁移和侵袭以及与肿瘤生长相关的血管生成为特征的疾病。本发明工艺提供的化合物包括 "谱系选择性 "激酶调节剂，即抑制、调节和/或调控包括表皮生长因子受体和表皮生长因子受体在内的各受体型酪氨酸激酶亚家族信号转导的化合物。
• Compounds, pharmaceutical compositions thereof and their use in treating cancer
  申请人：Symphony Evolution, Inc.

  公开号：EP2277867A2

  公开（公告）日：2011-01-26

  The present invention provides compounds which can modulate receptor kinase activity, particularly ephrin and EGFR, pharmaceutical compositions thereof and such compounds for use in treating cancer. The compounds comprise N-(3,4-dichloro-2-fluorophenyl)-7-([(3aR,5r,6aS)-2-methyloctahydrocyclopenta [c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine and N-(3,4-dichloro-2-fluorophenyl)-7-([(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine.

  本发明提供了可调节受体激酶活性的化合物，特别是表皮生长因子受体和表皮生长因子受体，其药物组合物和用于治疗癌症的此类化合物。这些化合物包括N-(3,4-二氯-2-氟苯基)-7-([(3aR,5r,6aS)-2-甲基八氢环戊并[c]吡咯-5-基]甲基}氧基)-6-(甲氧基)喹唑啉-4-胺和N-(3、N-(3,4-二氯-2-氟苯基)-7-([(3aR,5s,6aS)-2-甲基八氢环戊并[c]吡咯-5-基]甲基}氧基)-6-(甲氧基)喹唑啉-4-胺。