(4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-<2-(mesyloxy)ethyl>-2,2-dimethyloxazolidine | 124577-56-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: (4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-<2-(mesyloxy)ethyl>-2,2-dimethyloxazolidine
• 英文别名: 2-[(4S,5S)-3-BOC-4-cyclohexylmethyl-2,2-dimethyl-5-oxazolidinyl]ethyl methanesulfonate；(4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-[2-(mesyloxy)ethyl]-2,2-dimethyloxazolidine；tert-butyl (4S,5S)-4-(cyclohexylmethyl)-2,2-dimethyl-5-(2-methylsulfonyloxyethyl)-1,3-oxazolidine-3-carboxylate
• CAS: 124577-56-6
• 化学式: C₂₀H₃₇NO₆S
• 分子量: 419.583
• InChiKey: HCTRYIBARQVOSV-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  90.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-<2-(mesyloxy)ethyl>-2,2-dimethyloxazolidine 在 potassium tert-butylate 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 0.5h， 以78%的产率得到(4S,5S)-3-tert-butoxycarbonyl-4-cyclohexylmethyl-2,2-dimethyl-5-vinyloxazolidine
  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 sodium tetrahydroborate 、 二甲基硫 、 对甲苯磺酸 、 臭氧 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 (4S,5S)-3-(tert-butoxycarbonyl)-4-(cyclohexylmethyl)-5-<2-(mesyloxy)ethyl>-2,2-dimethyloxazolidine
  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

• Peptide analogues
  申请人：——

  公开号：US05401722A1

  公开（公告）日：1995-03-28

  New peptide analogues of the formula I R.sup.1 --Z--NR.sup.2 --CHR.sup.3 --CR.sup.4 --(CH.sub.2).sub.o --(CR.sup.5).sub.t --(CH.sub.2).sub.v --CE--C.sub.w H.sub.2w --R.sup.6 I in which R.sup.1 to R.sup.6 Z, E, o, t and w have the meanings described herein, and the salts thereof, inhibit the activity of human plasma renin.

  公式I的新肽类似物 R.sup.1 --Z--NR.sup.2 --CHR.sup.3 --CR.sup.4 --(CH.sub.2).sub.o --(CR.sup.5).sub.t --(CH.sub.2).sub.v --CE--C.sub.w H.sub.2w --R.sup.6 I及其盐，可以抑制人类血浆肾素的活性。其中R.sup.1到R.sup.6，Z，E，o，t和w的含义如此处所述。
• Peptid-Analoga mit renininhibierender Aktivität
  申请人：MERCK PATENT GmbH

  公开号：EP0446485B1

  公开（公告）日：1995-09-06
• US5401722A
  申请人：——

  公开号：US5401722A

  公开（公告）日：1995-03-28
• Renin inhibitors containing new P1-P1' dipeptide mimetics with heterocycles in P1'
  作者：Peter Raddatz、Alfred Jonczyk、Klaus Otto Minck、Friedrich Rippmann、Christine Schittenhelm、Claus Jochen Schmitges

  DOI：10.1021/jm00097a010

  日期：1992.9

  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.