tert-butyl N-[(2R)-1-[[(2S,3S)-1-cyclohexyl-3-hydroxy-5-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pentan-2-yl]amino]-3-methylsulfanyl-1-oxopropan-2-yl]carbamate | 1055038-40-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl N-[(2R)-1-[[(2S,3S)-1-cyclohexyl-3-hydroxy-5-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pentan-2-yl]amino]-3-methylsulfanyl-1-oxopropan-2-yl]carbamate
• CAS: 1055038-40-8
• 化学式: C₂₃H₄₀N₄O₄S₃
• 分子量: 532.793
• InChiKey: LZJCILRQOINEGK-FHWLQOOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  34
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  192
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2R)-1-[[(2S,3S)-1-cyclohexyl-3-hydroxy-5-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pentan-2-yl]amino]-3-methylsulfanyl-1-oxopropan-2-yl]carbamate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 (R)-2-Amino-N-[(1S,2S)-1-cyclohexylmethyl-2-hydroxy-4-(5-methyl-[1,3,4]thiadiazol-2-ylsulfanyl)-butyl]-3-methylsulfanyl-propionamide; hydrochloride
  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：

  (2S,3S)-2-(tert-butoxycarboxamido)-1-cyclohexyl-5-hexen-3-ol 在 N-甲基吗啉 、 盐酸 、 sodium tetrahydroborate 、 二甲基硫 、 sodium hydride 、 1-羟基苯并三唑 、 对甲苯磺酸 、 臭氧 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.5h， 生成 tert-butyl N-[(2R)-1-[[(2S,3S)-1-cyclohexyl-3-hydroxy-5-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]pentan-2-yl]amino]-3-methylsulfanyl-1-oxopropan-2-yl]carbamate
  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