3-<(tert-butyloxy)carbonyl>-4-(cyclohexylmethyl)-2,2-dimethyl-5-vinyloxazolidine | 122226-01-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 3-<(tert-butyloxy)carbonyl>-4-(cyclohexylmethyl)-2,2-dimethyl-5-vinyloxazolidine
• 英文别名: 3-(t-Butyloxycarbonyl)-4-(cyclohexylmethyl)-2,2-dimethyl-5-vinyloxazolidine；tert-butyl 4-(cyclohexylmethyl)-5-ethenyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 122226-01-1
• 化学式: C₁₉H₃₃NO₃
• 分子量: 323.476
• InChiKey: FDHUDLULPYXQKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-<(tert-butyloxy)carbonyl>-4-(cyclohexylmethyl)-2,2-dimethyl-5-vinyloxazolidine 在 palladium on activated charcoal 盐酸 、 lithium aluminium tetrahydride 、 乙醇 、 氢气 、 锌 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 50.0 ℃ 、405.3 kPa 条件下， 反应 18.0h， 生成 [(2S,4S,5R,6S)-7-cyclohexyl-4,5-dihydroxy-2-methyl-6-[(4-methylphenyl)sulfonylamino]heptyl] 4-methylbenzenesulfonate
  参考文献：
  名称：

  Potent, low molecular weight renin inhibitors containing a C-terminal heterocycle: hydrogen bonding at the active site

  摘要：

  A series of low-nanomolar renin inhibitors containing novel C-terminal heterocycles has been designed by formally cyclizing the C-terminus of a glycol-based inhibitor to the second hydroxyl. Molecular modeling suggests that the heterocyclic oxygen hydrogen bonds as an acceptor to the flap region of renin and that the second hydroxyl in the glycol-based inhibitors behaves similarly.

  DOI：

  10.1021/jm00168a009
• 作为产物：
  描述：

  2-甲氧基丙烯 、 (3RS,4S)-4-<(tert-butyloxy)carbonyl>-5-(cyclohexylmethyl)-3-hydroxy-1-pentene 在 4-甲基苯磺酸吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以100%的产率得到3-<(tert-butyloxy)carbonyl>-4-(cyclohexylmethyl)-2,2-dimethyl-5-vinyloxazolidine
  参考文献：
  名称：

  Potent, low molecular weight renin inhibitors containing a C-terminal heterocycle: hydrogen bonding at the active site

  摘要：

  A series of low-nanomolar renin inhibitors containing novel C-terminal heterocycles has been designed by formally cyclizing the C-terminus of a glycol-based inhibitor to the second hydroxyl. Molecular modeling suggests that the heterocyclic oxygen hydrogen bonds as an acceptor to the flap region of renin and that the second hydroxyl in the glycol-based inhibitors behaves similarly.

  DOI：

  10.1021/jm00168a009

文献信息

• Non-peptide renin inhibitors
  申请人：Abbott Laboratories

  公开号：US05268374A1

  公开（公告）日：1993-12-07

  The present invention relates to renin inhibiting compounds of the formula: ##STR1##

  本发明涉及公式为：##STR1## 的抑制肾素化合物。
• Renin-inhibiting peptidyl heterocycles
  申请人：ABBOTT LABORATORIES

  公开号：EP0307837A2

  公开（公告）日：1989-03-22

  A renin inhibiting compound of the formula: wherein A is a substituent; W is C=O, CHOH or NR₂ wherein R₂ is hydrogen or loweralkyl; U is C=O, CH₂ or NR₂ wherein R₂ is hydrogen or loweralkyl, with the proviso that when W is CHOH then U is CH₂ and with the proviso that U is C=O or CH₂ when W is NR₂; V is CH, C(OH) or C(halogen) with the proviso that V is CH when U is NR₂; R₁ is loweralkyl, cycloalkylalkyl, benzyl, (alpha, alpha)-dimethylbenzyl, 4-methoxybenzyl, halobenzyl, 4-hydroxybenzyl, (1-naphthyl)methyl, (2-naphthyl)methyl, (unsubstituted heterocyclic)methyl, (substituted heterocyclic)methyl, phenethyl, 1-benzyloxyethyl, phenoxy, thiophenoxy or anilino, provided that B is CH₂ or CHOH or A is hydrogen when R₁ is phenoxy, thiophenoxy or anilino; R₃ is loweralkyl, loweralkenyl, ((alkoxy)alkoxy)alkyl, carboxyalkyl, (thioalkoxy)alkyl, azidoalkyl, aminoalkyl, (alkyl)aminoalkyl, dialkylaminoalkyl, (alkoxy)(alkyl)aminoalkyl, (alkoxy)aminoalkyl, benzyl or heterocyclic ring substituted methyl; R₄ is loweralkyl, cycloalkylmethyl or benzyl; R₅ is OH or NH₂; and Z is a substituent. Also disclosed are compositions for and a method of treating hypertension, methods of making the renin inhibiting compounds and intermediates useful in making the renin inhibiting compounds.

  一种式的肾素抑制化合物： 其中 A 是取代基；W 是 C=O、CHOH 或 NR₂，其中 R₂ 是氢或低级烷基；U 是 C=O、CH₂ 或 NR₂，其中 R₂ 是氢或低级烷基，但当 W 是 CHOH 时，U 是 CH₂，当 W 是 NR₂ 时，U 是 C=O 或 CH₂；V 是 CH、C(OH) 或 C(卤素)，但当 U 是 NR₂ 时，V 是 CH；(取代杂环)甲基、苯乙基、1-苄氧基乙基、苯氧基、噻吩氧基或苯胺基，但当 R₁ 为苯氧基、噻吩氧基或苯胺基时，B 为 CH₂ 或 CHOH 或 A 为氢；R₃ 是低级烷基、低级烯基、((烷氧基)烷氧基)烷基、羧基烷基、(硫代烷氧基)烷基、叠氮烷基、氨基烷基、(烷基)氨基烷基、二烷基氨基烷基、(烷氧基)(烷基)氨基烷基、(烷氧基)氨基烷基、苄基或杂环取代的甲基；R₄ 是低级烷基、环烷基甲基或苄基；R₅ 是 OH 或 NH₂；Z 是取代基。 还公开了治疗高血压的组合物和方法、制造肾素抑制化合物的方法以及制造肾素抑制化合物的中间体。
• Glaucoma treatment
  申请人：ABBOTT LABORATORIES

  公开号：EP0311012A2

  公开（公告）日：1989-04-12

  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: wherein A is a substituent; W is CO or CHOH and U is CH₂ or NR₂ wherein R₂ is hydrogen or loweralkyl; with the proviso that when W is CHOH then U is CH₂; R₁ 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; R₃ is loweralkyl, loweralkenyl, ((alkoxy)alkoxy)alkyl, carboxyalkyl, (thioalkoxy)alkyl, benzyl or heterocyclic ring substituted methyl; and R₄ 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.

  一种治疗或降低和/或控制眼压的方法和组合物，包括施用有效量的式中肾素抑制化合物： 其中 A 是取代基；W 是 CO 或 CHOH，U 是 CH₂ 或 NR₂，其中 R₂ 是氢或低级烷基；但当 W 是 CHOH 时，U 是 CH₂；R₁ 是低级烷基、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-咪唑酰基)甲基、苯乙基、1-苄氧基乙基、苯氧基、噻吩氧基或苯胺基；R₃ 是低级烷基、低级烯基、（（烷氧基）烷氧基）烷基、羧基烷基、（硫代烷氧基）烷基、苄基或杂环取代的甲基；以及 R₄ 是取代的氨基；或其药学上可接受的盐或酯。 还公开了用于治疗青光眼或降低和/或控制眼压的组合物、方法和试剂盒，其中肾素抑制化合物与β-肾上腺素能拮抗剂、类固醇抗炎剂或血管紧张素转换酶抑制化合物联合给药。
• Retroviral protease inhibitors
  申请人：ABBOTT LABORATORIES

  公开号：EP0342541A2

  公开（公告）日：1989-11-23

  A retroviral protease inhibiting compound of the formula: or a pharmaceutically acceptable salt, prodrug or ester thereof.

  一种抑制逆转录病毒蛋白酶的式化合物： 或其药学上可接受的盐、原药或酯。
• Method for treating renal disease
  申请人：ABBOTT LABORATORIES

  公开号：EP0440102A1

  公开（公告）日：1991-08-07

  The present invention relates to the use of renin inhibitors and to renin inhibitor compositions for prevention, treatment, inhibition or reversal of renal dysfunction or disease, especially renal failure.

  本发明涉及肾素抑制剂和肾素抑制剂组合物在预防、治疗、抑制或逆转肾功能障碍或疾病，特别是肾衰竭方面的用途。