(3S,4S)-1-<<(2-methylpropyl)carbonyl>amino>-3-hydroxy-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexylpentane | 108868-59-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (3S,4S)-1-<<(2-methylpropyl)carbonyl>amino>-3-hydroxy-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexylpentane
• 英文别名: (3S,4S)-1-(2 Methylpropylcarbonylamino)-3-hydroxy-4-t-butyloxycarbonylamino-5-cyclohexylpentane；(3S,4S)-1-(2-Methylpropylcarbonylamino)-3-hydroxy-4-t-butyloxycarbonylamino-5-cyclohexylpentane；(3S,4S)-1-{[(2-methylpropyl)carbonyl]amino}-3-hydroxy-4-[(tert-butyloxycarbonyl)amino]-5-cyclohexylpentane；tert-butyl N-[(2S,3S)-1-cyclohexyl-3-hydroxy-5-(3-methylbutanoylamino)pentan-2-yl]carbamate
• CAS: 108868-59-3
• 化学式: C₂₁H₄₀N₂O₄
• 分子量: 384.56
• InChiKey: RCNIQDVEJBLNED-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,4S)-1-<<(2-methylpropyl)carbonyl>amino>-3-hydroxy-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexylpentane 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 N-[(3S,4S)-4-amino-5-cyclohexyl-3-hydroxypentyl]-3-methylbutanamide
  参考文献：
  名称：

  Novel renin inhibitors containing analogs of statine retro-inverted at the C-termini. Specificity at the P2 histidine site

  摘要：

  Substituted 1,3- and 1,4-diamines were prepared from epoxides derived from Boc-leucine or Boc-cyclohexylalanine. These diamines were incorporated into renin inhibitors (IC50 = 4-1500 nM) replacing the Leu-Val scissile bond in small peptide analogues of angiotensinogen. Replacement of the P2 histidine imidazole with other heterocycles maintained or enhanced binding while changing the overall basicity of the inhibitor. Finally, substitution of O-methyltyrosine for the P3 phenylalanine suppressed chymotrypsin cleavage of the P3-P2 bond.

  DOI：

  10.1021/jm00390a018
• 作为产物：
  描述：

  2-甲基-2-丙基[(2S)-1-环己基-3-氧代-2-丙基]氨基甲酸酯 在 镍 氨 、 氢气 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， -78.0 ℃ 、303.98 kPa 条件下， 反应 1.42h， 生成 (3S,4S)-1-<<(2-methylpropyl)carbonyl>amino>-3-hydroxy-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexylpentane
  参考文献：
  名称：

  Novel renin inhibitors containing analogs of statine retro-inverted at the C-termini. Specificity at the P2 histidine site

  摘要：

  Substituted 1,3- and 1,4-diamines were prepared from epoxides derived from Boc-leucine or Boc-cyclohexylalanine. These diamines were incorporated into renin inhibitors (IC50 = 4-1500 nM) replacing the Leu-Val scissile bond in small peptide analogues of angiotensinogen. Replacement of the P2 histidine imidazole with other heterocycles maintained or enhanced binding while changing the overall basicity of the inhibitor. Finally, substitution of O-methyltyrosine for the P3 phenylalanine suppressed chymotrypsin cleavage of the P3-P2 bond.

  DOI：

  10.1021/jm00390a018

文献信息

• Glaucoma treatment
  申请人：Abbott Laboratories

  公开号：US04927807A1

  公开（公告）日：1990-05-22

  A method and a composition for treating or reducing and/or controlling intraocular pressure comprising administering an effective amount of a renin inhibiting compound of the formula: ##STR1## wherein A is a substituent; W is CO or CHOH and U is CH.sub.2 or NR.sub.2 wherein R.sub.2 is hydrogen or loweralkyl; with the proviso that when W is CHOH then U is CH.sub.2 ; R.sub.1 is loweralkyl, cycloalkyl, benzyl, (alpha, alpha)-dimethylbenzyl, 4-hydroxybenzyl, 4-methoxybenzyl, halobenzyl, (1-naphthyl)methyl, (2-naphthyl)methyl, (4-imidazoyl)methyl, phenethyl, 1-benzyloxyethyl, phenoxy, thiophenoxy or anilino; R.sub.3 is loweralkyl, loweralkenyl, ((alkoxy)alkoxy)alkyl, carboxyalkyl, (thioalkoxy)alkyl, benzyl or heterocyclic ring substituted methyl; and R.sub.4 is a substituted amino group; or pharmaceutically acceptable salts or esters thereof. Also disclosed are compositions, methods and kits for treating glaucoma or reducing and/or controlling intraocular pressure wherein the renin inhibiting compound is administered in combination with a beta-adrenergic antagonist, a steroidal antiinflammatory agent or an angiotensin converting enzyme inhibiting compound.

  一种用于治疗或减少和/或控制眼内压的方法和组合物，包括给予有效量的下式化合物的抑制肾素的化合物：##STR1## 其中A是取代基；W是CO或CHOH，U是CH.sub.2或NR.sub.2，其中R.sub.2是氢或较低烷基；但当W是CHOH时，则U为CH.sub.2；R.sub.1是较低烷基，环烷基，苄基，(α，α)-二甲基苄基，4-羟基苄基，4-甲氧基苄基，卤代苄基，(1-萘基)甲基，(2-萘基)甲基，(4-咪唑基)甲基，苯乙基，1-苄氧基乙基，苯氧基，噻吩氧基或苯胺基；R.sub.3是较低烷基，较低烯基，((烷氧基)烷氧基)烷基，羧基烷基，(硫代烷氧基)烷基，苄基或杂环戒取代甲基；R.sub.4是取代氨基；或其药学上可接受的盐或酯。还公开了用于治疗青光眼或减少和/或控制眼内压的组合物、方法和试剂盒，其中抑制肾素的化合物与β-肾上腺素受体拮抗剂、类固醇抗炎药或抑制血管紧张素转换酶的化合物结合给予。
• US4927807A
  申请人：——

  公开号：US4927807A

  公开（公告）日：1990-05-22
• US5036051A
  申请人：——

  公开号：US5036051A

  公开（公告）日：1991-07-30
• US5059589A
  申请人：——

  公开号：US5059589A

  公开（公告）日：1991-10-22
• US5346887A
  申请人：——

  公开号：US5346887A

  公开（公告）日：1994-09-13