(4S,5S)-5-allyl-4-(cyclohexylmethyl)oxazolidin-2-one | 136057-66-4

• 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: (4S,5S)-5-allyl-4-(cyclohexylmethyl)oxazolidin-2-one
• 英文别名: trans-5-allyl-4-cyclohexylmethyl-2-oxazolidinone；(4S,5S)-5-allyl-4-cyclohexylmethyl-1,3-oxazolidin-2-one；(4S,5S)-4-(cyclohexylmethyl)-5-prop-2-enyl-1,3-oxazolidin-2-one
• CAS: 136057-66-4
• 化学式: C₁₃H₂₁NO₂
• 分子量: 223.315
• InChiKey: YLAFWBPVIWJDPH-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  二碳酸二叔丁酯 、 (4S,5S)-5-allyl-4-(cyclohexylmethyl)oxazolidin-2-one 在 正丁基锂 作用下， 以93%的产率得到(4S,5S)-5-Allyl-4-cyclohexylmethyl-2-oxo-oxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Lewis acid-promoted direct substitution of 4-methoxy- and 4-phenylthio-2-oxazolidinones by alkyl cuprates. Facile preparation of (3s,4s)-statine and (3s,4s)-cyclohexylstatine.

  摘要：

  Treatment of 4-methoxy- and 4-phenylthio-2-oxazolidinones with a combination of cuprates and BF3 results in smooth formation of 4-alkyl and 4-aryl derivatives in high yield. By this method, the titled compounds of biological interest are readily synthesized from (4S,5S)-5-allyl-4-methoxy (or 4-phenylthio)-2-oxazolidinones stereoselectively.

  DOI：

  10.1016/0040-4039(91)80822-n
• 作为产物：
  描述：

  (2S,3S)-2-(tert-butoxycarboxamido)-1-cyclohexyl-5-hexen-3-ol 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 以83%的产率得到(4S,5S)-5-allyl-4-(cyclohexylmethyl)oxazolidin-2-one
  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

• DIOXACYCLOALKANE COMPOUND WITH RENIN-INHIBITING ACTIVITY
  申请人：JAPAN TOBACCO INC.

  公开号：EP0656356A1

  公开（公告）日：1995-06-07

  A dioxacycloalkane compound represented by general formula [1], a pharmaceutically acceptable salt thereof, an intermediate for producing the compound, and a process for producing the intermediate. The compound [1] has a potent activity of inhibiting renin and a persistent hypotensive effect by peroral administration, thus being useful as a hypotensive and a remedy for cardiac insufficiency. General formula [1] wherein A represents [a] or [b]; W represents [c], [d] or [e], X represents -CO- or -SO₂-; Y represents -CH₂, -O- or -NR²⁵-; R¹ represents aralkyl which may be substituted by lower alkoxy; R² represents hydrogen or lower alkyl; R³ represents -(CH₂)d-SR²⁶ or [f]; R⁴ and R⁵ represent each hydrogen or lower alkyl; and E represents -C(R²⁹)(R³⁰)- or -CH₂CH₂-.

  一种由通式[1]表示的二氧环烷烃化合物、其药学上可接受的盐、生产该化合物的中间体以及生产该中间体的工艺。该化合物[1]具有抑制肾素的强效活性，口服给药具有持续降压作用，因此可用作降压药和治疗心功能不全的药物。通式[1] 其中 A 代表[a]或[b]；W 代表[c]、[d]或[e]，X 代表-CO-或-SO₂-；Y 代表-CH₂、-O-或-NR²⁵-；R¹ 代表可被低级烷氧基取代的芳烷基；R² 代表氢或低级烷基；R³ 代表-(CH₂)d-SR²⁶ 或 [f]；R⁴ 和 R⁵ 各自代表氢或低级烷基；以及 E 代表-C(R²⁹)(R³⁰)- 或 -CH₂CH₂-。
• US5750696A
  申请人：——

  公开号：US5750696A

  公开（公告）日：1998-05-12
• 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.
• Lewis acid-promoted direct substitution of 4-methoxy- and 4-phenylthio-2-oxazolidinones by alkyl cuprates. Facile preparation of (3s,4s)-statine and (3s,4s)-cyclohexylstatine.
  作者：Seigo Ishibuchi、Yumi Ikematsu、Tadao Ishizuka、Takehisa Kunieda

  DOI：10.1016/0040-4039(91)80822-n

  日期：1991.7

  Treatment of 4-methoxy- and 4-phenylthio-2-oxazolidinones with a combination of cuprates and BF3 results in smooth formation of 4-alkyl and 4-aryl derivatives in high yield. By this method, the titled compounds of biological interest are readily synthesized from (4S,5S)-5-allyl-4-methoxy (or 4-phenylthio)-2-oxazolidinones stereoselectively.