| 143122-17-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• CAS: 143122-17-2
• 化学式: C₁₆H₂₆N₂OS*ClH
• 分子量: 330.922
• InChiKey: SHUGRZLCVMMZTF-YYLIZZNMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.64
• 重原子数：
  21.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  59.14
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 [(2S)-1-[[(2S)-1-[[(2S,3S)-1-cyclohexyl-3-hydroxy-5-pyridin-2-ylsulfanylpentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl] 4-[(2-methylpropan-2-yl)oxycarbonylamino]piperidine-1-carboxylate
  参考文献：
  名称：

  Renin inhibitors containing new P1-P1' dipeptide mimetics with heterocycles in P1'

  摘要：

  A series of renin inhibitors containing new P1-P1' dipeptide mimetics are presented The P1-P1' mimetics were obtained from (4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-[(omega-mesyloxy)alkyl]-2,2-dimethyloxazolidines 5b, 9, and 11b by nucleophilic substitution of the mesylate groups with the sodium salts of mercapto- and hydroxyheterocycles. Removal of the protecting groups and stepwise acylations with amino acid derivatives provided renin inhibitors with a length of a tripeptide. Replacement of P2 histidine by other amino acids maintained or enhanced renin inhibitory potency. By alteration of P3 phenylalanine, compounds with IC50 values in the nanomolar range and stability against chymotrypsin were obtained. Finally, the effect of the C-terminal heterocycle on the renin inhibition was studied. Compound XVII was examined in vivo for its hypotensive effects. In salt-depleted cynomolgus monkeys, XVII inhibited plasma renin activity and lowered blood pressure after oral administration of a dose of 10 mg/kg.

  DOI：

  10.1021/jm00097a010
• 作为产物：
  描述：

  (4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-2,2-dimethyloxazolidine-5-ethanol 在 盐酸 、 sodium hydride 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 21.5h， 生成
  参考文献：
  名称：

  Renin inhibitors containing new P1-P1' dipeptide mimetics with heterocycles in P1'

  摘要：

  A series of renin inhibitors containing new P1-P1' dipeptide mimetics are presented The P1-P1' mimetics were obtained from (4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-[(omega-mesyloxy)alkyl]-2,2-dimethyloxazolidines 5b, 9, and 11b by nucleophilic substitution of the mesylate groups with the sodium salts of mercapto- and hydroxyheterocycles. Removal of the protecting groups and stepwise acylations with amino acid derivatives provided renin inhibitors with a length of a tripeptide. Replacement of P2 histidine by other amino acids maintained or enhanced renin inhibitory potency. By alteration of P3 phenylalanine, compounds with IC50 values in the nanomolar range and stability against chymotrypsin were obtained. Finally, the effect of the C-terminal heterocycle on the renin inhibition was studied. Compound XVII was examined in vivo for its hypotensive effects. In salt-depleted cynomolgus monkeys, XVII inhibited plasma renin activity and lowered blood pressure after oral administration of a dose of 10 mg/kg.

  DOI：

  10.1021/jm00097a010

文献信息

• Non-peptide Renin Inhibitors Containing 2-(((3-Phenylpropyl)phosphoryl)oxy)alkanoic Acid Moieties as P2-P3 Replacements
  作者：Peter Raddatz、Klaus-Otto Minck、Friedrich Rippmann、Claus-Jochen Schmitges

  DOI：10.1021/jm00030a008

  日期：1994.2

  A series of novel renin inhibitors containing 2-(((3-phenylpropyl)phosphoryl)oxy) alkanoic acid moieties as P-2-P-3 surrogates are presented. The P-2-P-3 mimetics were obtained from (omega-phenylalkyl)phosphinic acids la-c and 2-hydroxyalkanoic acid benzyl esters 2a-f by N,N'-dicyclohexylcarbodiimide-mediated coupling and subsequent oxidation with sodium metaperjodate. Ester cleavage of these derivatives and coupling with P-1-P-1' transition-state mimetics I-VII provided highly selective compounds with inhibitory potencies in the lower nanomolar range. Small renin inhibitors, such as analogues 8c and 8h with molecular weights of 539 and 537, respectively, could be prepared. These compounds exhibited IC50 values of about 20 nM against human plasma renin. Compound 7i was examined in vivo for its hypotensive effect. In salt-depleted cynomolgus monkeys, 7i inhibited plasma renin activity almost completely and lowered blood pressure after oral administration of a dose of 30 mg/kg.