(2R,3S)-3-Amino-4-cyclohexyl-1-[1-(2-pyridin-4-yl-ethyl)-1H-tetrazol-5-ylsulfanyl]-butan-2-ol | 769922-16-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (2R,3S)-3-Amino-4-cyclohexyl-1-[1-(2-pyridin-4-yl-ethyl)-1H-tetrazol-5-ylsulfanyl]-butan-2-ol
• 英文别名: (2R,3S)-3-amino-4-cyclohexyl-1-[1-(2-pyridin-4-ylethyl)tetrazol-5-yl]sulfanylbutan-2-ol
• CAS: 769922-16-9
• 化学式: C₁₈H₂₈N₆OS
• 分子量: 376.526
• InChiKey: UVCYUUNBNZPCRA-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2R,3S)-3-Amino-4-cyclohexyl-1-[1-(2-pyridin-4-yl-ethyl)-1H-tetrazol-5-ylsulfanyl]-butan-2-ol 在 氨 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 23.5h， 生成 5-({(2R,3S)-3-[(Boc-L-phenylalanyl-L-histidyl)amino]-4-cyclohexyl-2-hydroxy-1-butyl}sulfonyl)-1-[2-(1-oxo-4-pyridyl)ethyl]-1H-tetrazole
  参考文献：
  名称：

  Renin inhibitors containing C-termini derived from mercaptoheterocycles

  摘要：

  A series of transition-state analogues having heterocyclylthio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. Oxidation of the thioether to sulfone was also investigated. Several of the compounds, especially those derived from N1-substituted-5-mercaptotetrazoles or N4-substituted-3-mercapto-5-(trifluoromethyl)-1,2,4-triazoles, were moderately potent inhibitors of human plasma renin, having IC50 values of 30-40 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys at 0.3-1.2 mg/kg, they reduced plasma renin activity by 75-98%. However, this inhibition and the accompanying drop in blood pressure were of short duration.

  DOI：

  10.1021/jm00089a023
• 作为产物：
  描述：

  (2R,3S)-3-(t-butoxycarbonylamino)-4-cyclohexyl-1,2-epoxybutane 在 盐酸 、 三乙胺 作用下， 以 乙二醇甲醚 为溶剂， 反应 6.0h， 生成 (2R,3S)-3-Amino-4-cyclohexyl-1-[1-(2-pyridin-4-yl-ethyl)-1H-tetrazol-5-ylsulfanyl]-butan-2-ol
  参考文献：
  名称：

  Renin inhibitors containing C-termini derived from mercaptoheterocycles

  摘要：

  A series of transition-state analogues having heterocyclylthio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. Oxidation of the thioether to sulfone was also investigated. Several of the compounds, especially those derived from N1-substituted-5-mercaptotetrazoles or N4-substituted-3-mercapto-5-(trifluoromethyl)-1,2,4-triazoles, were moderately potent inhibitors of human plasma renin, having IC50 values of 30-40 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys at 0.3-1.2 mg/kg, they reduced plasma renin activity by 75-98%. However, this inhibition and the accompanying drop in blood pressure were of short duration.

  DOI：

  10.1021/jm00089a023

文献信息

• Long Acting Biologically Active Conjugates
  申请人：Silva Abelardo

  公开号：US20070207952A1

  公开（公告）日：2007-09-06

  The invention provides biologically active compounds that may be reacted with macromolecules, such as albumin, to form covalent linked complexes wherein the resulting complexes exhibit a desired biological activity in vivo. More specifically, the complexes are isolated complexes comprising a biologically active moiety covalently bound to a linking group and a protein. The complexes are prepared by conjugating a biologically active moiety, for example, a renin inhibitor or a viral fusion inhibitor peptide, with purified and isolated protein. The complexes have extended lifetimes in the bloodstream as compared to the unconjugated molecule, and exhibit biological activity for extended periods of time as compared to the unconjugated molecule. The invention also provides anti-viral compounds that are inhibitors of viral infection and/or exhibit anti-fusiogenic properties. In particular, this invention provides compounds having inhibiting activity against viruses such as human immunodeficiency virus (HIV), respiratory syncytial virus (RSV), human parainfluenza virus (HPV), measles virus (MeV), and simian immunodeficiency virus (SIV) and that have extended duration of action for the treatment of viral infections.
• Renin inhibitors containing C-termini derived from mercaptoheterocycles
  作者：Wallace T. Ashton、Christine L. Cantone、Laura C. Meurer、Richard L. Tolman、William J. Greenlee、Arthur A. Patchett、Robert J. Lynch、Terry W. Schorn、John F. Strouse、Peter K. S. Siegl

  DOI：10.1021/jm00089a023

  日期：1992.5

  A series of transition-state analogues having heterocyclylthio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio derivatives. Oxidation of the thioether to sulfone was also investigated. Several of the compounds, especially those derived from N1-substituted-5-mercaptotetrazoles or N4-substituted-3-mercapto-5-(trifluoromethyl)-1,2,4-triazoles, were moderately potent inhibitors of human plasma renin, having IC50 values of 30-40 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys at 0.3-1.2 mg/kg, they reduced plasma renin activity by 75-98%. However, this inhibition and the accompanying drop in blood pressure were of short duration.