3-<3(R)-<3-(tert-butyloxycarbonyl)-4(S)-cyclohexylmethyl)-2,2-dimethyl-5(R)-oxazolidinyl>-3-hydroxy-2(R)-isopropyl-1-oxopropyl>-4(R)-methyl-5(S)-phenyl-2-oxazolidinone | 112190-42-8

• 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-<3(R)-<3-(tert-butyloxycarbonyl)-4(S)-cyclohexylmethyl)-2,2-dimethyl-5(R)-oxazolidinyl>-3-hydroxy-2(R)-isopropyl-1-oxopropyl>-4(R)-methyl-5(S)-phenyl-2-oxazolidinone
• 英文别名: 3-(3(R)-(3-(tert-butyloxycarbonyl)-2,2-dimethyl-4(S)-(cyclohexylmethyl)-5(R)-oxazolidinyl)-3-hydroxy-2(R)-isopropyl-1-oxopropyl)-4(R)-methyl-5(S)-phenyl-2-oxazolidinone；tert-butyl (4S,5R)-4-(cyclohexylmethyl)-5-[(1R,2R)-1-hydroxy-3-methyl-2-[(4R,5S)-4-methyl-2-oxo-5-phenyl-1,3-oxazolidine-3-carbonyl]butyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 112190-42-8
• 化学式: C₃₃H₅₀N₂O₇
• 分子量: 586.769
• InChiKey: MOMFXIQMHBSZPU-ATADLHIKSA-N

物化性质

• 沸点：
  693.5±55.0 °C(Predicted)
• 密度：
  1.133±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-<3(R)-<3-(tert-butyloxycarbonyl)-4(S)-cyclohexylmethyl)-2,2-dimethyl-5(R)-oxazolidinyl>-3-hydroxy-2(R)-isopropyl-1-oxopropyl>-4(R)-methyl-5(S)-phenyl-2-oxazolidinone 在 ethandithiol 、 ruthenium trichloride 、 diethylphosphoryl cyanide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 过碘酸 、 N,N-二异丙基乙胺 、 乙酰氯 、 三氟乙酸 作用下， 以 甲醇 、 四氯化碳 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 35.25h， 生成 (2R,3R,4R,5S)-6-Cyclohexyl-3,4-dihydroxy-5-{(S)-3-(1H-imidazol-4-yl)-2-[2-(naphthalen-1-yloxy)-acetylamino]-propionylamino}-2-isopropyl-hexanoic acid {(1S,2S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butyl}-amide
  参考文献：
  名称：

  Inhibitors of the protease from human immunodeficiency virus: design and modeling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective antiviral activity

  摘要：

  The peptidomimetic template and the dihydroxyethylene isostere insert that were applied successfully to the design of renin inhibitors have been extended to the related protease from human immunodeficiency virus (HIV). The present report describes the structure-activity study leading to the identification of an inhibitor with a K(i) of < 1 nM for the HIV type-1 protease (compound II). This compound, containing a diol insert, is highly effective in blocking polyprotein processing in in vitro cell culture assays. Results obtained from kinetic analysis, studies of the stereochemistry of the insert, and modeling have led to insights as to the requisites involved in the active site-inhibitor interaction.

  DOI：

  10.1021/jm00112a005
• 作为产物：
  描述：

  4(R)-methyl-3-(1-oxo-3-methylbutyl)-5(S)-phenyl-2-oxazolidinone 、 tert-butyl (4S,5R)-4-(cyclohexylmethyl)-5-formyl-2,2-dimethyl-3-oxazolidinecarboxylate 生成 3-<3(R)-<3-(tert-butyloxycarbonyl)-4(S)-cyclohexylmethyl)-2,2-dimethyl-5(R)-oxazolidinyl>-3-hydroxy-2(R)-isopropyl-1-oxopropyl>-4(R)-methyl-5(S)-phenyl-2-oxazolidinone
  参考文献：
  名称：

  Inhibitors of the protease from human immunodeficiency virus: design and modeling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective antiviral activity

  摘要：

  The peptidomimetic template and the dihydroxyethylene isostere insert that were applied successfully to the design of renin inhibitors have been extended to the related protease from human immunodeficiency virus (HIV). The present report describes the structure-activity study leading to the identification of an inhibitor with a K(i) of < 1 nM for the HIV type-1 protease (compound II). This compound, containing a diol insert, is highly effective in blocking polyprotein processing in in vitro cell culture assays. Results obtained from kinetic analysis, studies of the stereochemistry of the insert, and modeling have led to insights as to the requisites involved in the active site-inhibitor interaction.

  DOI：

  10.1021/jm00112a005

文献信息

• Non-peptide renin inhibitors
  申请人：ABBOTT LABORATORIES

  公开号：EP0364804A1

  公开（公告）日：1990-04-25

  A renin inhibiting compound of the formula: wherein A is a substituent; R1 is hydrogen, loweralkyl, substituted loweralkyl or loweralkenyl; X is CH2, CHOH, C(O), O, S, S(O), S02, NH, N(O) or -P(O)O-; R3 is loweralkyl, loweralkenyl or substituted loweralkyl; and T is mimic of the Leu-Val cleavage site of angiotensinogen; or a pharmaceutically acceptable salt, ester or prodrug thereof.

  式中的肾素抑制化合物： 其中 A 是取代基；R1 是氢、低级烷基、取代的低级烷基或低级烯基；X 是 CH2、CHOH、C(O)、O、S、S(O)、S02、NH、N(O)或-P(O)O-；R3 是低级烷基、低级烯基或取代的低级烷基；T 是血管紧张素原的 Leu-Val 裂解位点的模拟物；或其药学上可接受的盐、酯或原药。
• Heterocyclic peptide renin inhibitors
  申请人：ABBOTT LABORATORIES

  公开号：EP0365992A1

  公开（公告）日：1990-05-02

  A renin inhibiting compound of the formula: wherein X is N, O or CH; R1 is absent or a functional group; A and L are independently selected from absent, C = O, S02 and CH2; D is C = O, S02 or CH2; Y is N or CH; R2 is hydrogen, loweralkyl or substituted alkyl; Z is a functional group; R3 is loweralkyl or substituted alkyl; n is 0 or 1; and T is a mimic of the Leu-Val cleavage site of angiotensinogen; or a pharmaceutically acceptable salt, ester or prodrug thereof.

  一种式的肾素抑制化合物： 其中 X 是 N、O 或 CH；R1 是无或官能团；A 和 L 独立选自无、C = O、S02 和 CH2；D 是 C = O、S02 或 CH2；Y 是 N 或 CH；R2 是氢、低级烷基或取代的烷基；Z 是官能团；R3 是低级烷基或取代的烷基；n 是 0 或 1；T 是血管紧张素原的 Leu-Val 裂解位点的模拟物；或其药学上可接受的盐、酯或原药。
• 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。
• Stereoselective syntheses of hydroxyethylene dipeptide isosteres
  作者：Steven A. Boyd、Robert A. Mantei、Chi Nung Hsiao、William R. Baker

  DOI：10.1021/jo00001a083

  日期：1991.1
• BOYD, STEVEN A.;MANTEI, ROBERT A.;HSIAO, CHI-NUNG;BAKER, WILLIAM R., J. ORG. CHEM., 56,(1991) N, C. 438-442
  作者：BOYD, STEVEN A.、MANTEI, ROBERT A.、HSIAO, CHI-NUNG、BAKER, WILLIAM R.

  DOI：——

  日期：——