(3S,4S)-1-amino-3-hydroxy-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexylpentane | 108868-55-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (3S,4S)-1-amino-3-hydroxy-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexylpentane
• 英文别名: (3S,4S)-1-amino-3-hydroxy-4-t-butyloxycarbonylamino-5-cyclohexylpentane；(3S,4S)-1-amino-3-hydroxy-4-[(tert-butyloxycarbonyl)amino]-5-cyclohexylpentane；tert-butyl N-[(2S,3S)-5-amino-1-cyclohexyl-3-hydroxypentan-2-yl]carbamate
• CAS: 108868-55-9
• 化学式: C₁₆H₃₂N₂O₃
• 分子量: 300.442
• InChiKey: BFZNYJXFKOIEDP-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  84.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,4S)-1-amino-3-hydroxy-4-<(tert-butyloxycarbonyl)amino>-5-cyclohexylpentane 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑一水物 、 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 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成
  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 、 lithium diisopropyl amide 作用下， 以 甲醇 为溶剂， -78.0 ℃ 、303.98 kPa 条件下， 反应 0.42h， 生成 (3S,4S)-1-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

• Angiotensinogen analogs
  申请人：Abbott Laboratories

  公开号：US04857507A1

  公开（公告）日：1989-08-15

  The invention relates to renin inhibiting compounds of the formula ##STR1## wherein A is hydrogen; loweralkyl; arylalkyl; OR.sub.10 or SR.sub.10 wherein R.sub.10 is hydrogen, loweralkyl or aminoalkyl; NR.sub.11 R.sub.12 wherein R.sub.11 and R.sub.12 are independently selected from hydrogen, loweralkyl, aminoalkyl, cyanoalkyl and hydroxyalkyl; ##STR2## wherein B is NH, alkylamino, S, O, CH.sub.2 or CHOH and R.sub.13 is loweralkyl, cycloalkyl, aryl, arylalkyl, alkoxy, alkenyloxy, hydroxyalkoxy, dihydroxyalkoxy, arylalkoxy, arylalkoxyalkyl, amino, alkylamino, dialkylamino, (hydroxyalkyl)(alkyl)amino, (dihydroxyalkyl)(alkyl)amino, aminoalkyl, alkoxycarbonylalkyl, carboxyalkyl, N-protected aminoalkyl, alkylaminoalkyl, (N-protected)(alkyl)aminoalkyl, dialkylaminoalkyl, (heterocyclic) alkyl or a substituted or unsubstituted heterocyclic; W is CO or CHOH and U is CH.sub.2 or NR.sub.2 with the proviso that when W is CHOH then U is CH.sub.2 ; R.sub.1 is loweralkyl, cycloaklylmethyl, benzyl, .alpha.,.alpha.-dimethylbenzyl, 4-methoxybenzyl, halobenzyl, (1-naphthyl)methyl, (2-naphthyl)methyl, (4-imidazoyl)-methyl, phenethyl, phenoxy, thiophenoxy or anilino; provided if R.sub.1 is phenoxy, thiophenoxy or anilino, B is CH.sub.2 or CHOH or A is hydrogen, R.sub.3 is loweralkyl, vinylloweralkyl, benzyl or heterocyclic ring substituted methyl, R.sub.5 is loweralkyl, cycloalkylmethyl or benzyl; R.sub.2 and R.sub.4 are independently selected from hydrogen and loweralkyl; R.sub.6 is CHOH or CO; R.sub.7 is CH.sub.2, CF.sub.2 or CF with the proviso that when R.sub.6 is CO, R.sub.7 is CF.sub.2 ; R.sub.8 is CH.sub.2, CHR.sub.14 wherein R.sub.14 is lower-alkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, or R.sub.7 and R.sub.8 taken together can be ##STR3## with the proviso that when R.sub.7 is CF.sub.2, R.sub.8 is CH.sub.2 ; E is O, S, SO, SO.sub.2, NR.sub.15 wherein R.sub.15 is hydrogen or loweralkyl or NR.sub.16 CO wherein R.sub.16 is hydrogen or loweralkyl; R.sub.9 is loweralkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl or an N-protected group, or E and R.sub.9 taken together can be N.sub.3, with the proviso that when E is NH, R.sub.9 is an N-protecting group; and pharmaceutically acceptable salts thereof.

  该发明涉及以下结构的肾素抑制化合物##STR1##其中A为氢；较低烷基；芳基烷基；OR.sub.10或SR.sub.10，其中R.sub.10为氢，较低烷基或氨基烷基；NR.sub.11 R.sub.12，其中R.sub.11和R.sub.12分别选择自氢，较低烷基，氨基烷基，氰基烷基和羟基烷基；##STR2##其中B为NH，烷基氨基，S，O，CH.sub.2或CHOH，R.sub.13为较低烷基，环烷基，芳基，芳基烷基，烷氧基，烯基氧基，羟基烷氧基，二羟基烷氧基，芳基烷氧基，芳基烷氧基烷基，氨基，烷基氨基，二烷基氨基，(羟基烷基)(烷基)氨基，(二羟基烷基)(烷基)氨基，氨基烷基，烷氧羰基烷基，羧基烷基，N-保护氨基烷基，烷基氨基烷基，(N-保护)(烷基)氨基烷基，二烷基氨基烷基，(杂环)烷基或取代或未取代的杂环；W为CO或CHOH，U为CH.sub.2或NR.sub.2，但当W为CHOH时，U为CH.sub.2；R.sub.1为较低烷基，环烷基甲基，苄基，.alpha.，.alpha.-二甲基苄基，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，苯氧基，噻吩氧基或苯胺基；但如果R.sub.1为苯氧基，噻吩氧基或苯胺基，B为CH.sub.2或CHOH或A为氢，R.sub.3为较低烷基，烯基较低烷基，苄基或杂环环取代甲基，R.sub.5为较低烷基，环烷基甲基或苄基；R.sub.2和R.sub.4分别选择自氢和较低烷基；R.sub.6为CHOH或CO；R.sub.7为CH.sub.2，CF.sub.2或CF，但当R.sub.6为CO时，R.sub.7为CF.sub.2；R.sub.8为CH.sub.2，CHR.sub.14，其中R.sub.14为较低烷基，环烷基，环烷基烷基，芳基或芳基烷基，或R.sub.7和R.sub.8一起可以是##STR3##但当R.sub.7为CF.sub.2时，R.sub.8为CH.sub.2；E为O，S，SO，SO.sub.2，NR.sub.15，其中R.sub.15为氢或较低烷基或NR.sub.16 CO，其中R.sub.16为氢或较低烷基；R.sub.9为较低烷基，环烷基，环烷基烷基，芳基，芳基烷基或N-保护基，或E和R.sub.9一起可以是N.sub.3，但当E为NH时，R.sub.9为N-保护基；及其药学上可接受的盐。
• 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。
• PEPTIDE ANALOGS
  申请人：DELLARIA, Joseph

  公开号：EP0258289A1

  公开（公告）日：1988-03-09
• EP0258289A4
  申请人：——

  公开号：EP0258289A4

  公开（公告）日：1991-01-02
• US4857507A
  申请人：——

  公开号：US4857507A

  公开（公告）日：1989-08-15