6R-[1R-tert-butoxycarbonylamino-2-(4-fluoro-phenyl)-ethyl]-4-cyanomethylene-tetrahydro-pyran-2S-carboxylic acid methyl ester | 623143-72-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6R-[1R-tert-butoxycarbonylamino-2-(4-fluoro-phenyl)-ethyl]-4-cyanomethylene-tetrahydro-pyran-2S-carboxylic acid methyl ester
• CAS: 623143-72-6
• 化学式: C₂₂H₂₇FN₂O₅
• 分子量: 418.465
• InChiKey: PLDFUEPPNGZYBM-QRVBRYPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.43
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  97.65
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  6R-[1R-tert-butoxycarbonylamino-2-(4-fluoro-phenyl)-ethyl]-4-cyanomethylene-tetrahydro-pyran-2S-carboxylic acid methyl ester 在 镍 N-甲基吗啉 、 lithium hydroxide 、 ammonium hydroxide 、 sodium tetrahydroborate 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 、 mercury dichloride 、 palladium dichloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 10.0h， 生成 6R-[1R-amino-2-(4-fluoro-phenyl)-ethyl]-4-(2-guanidino-ethyl)-tetrahydro-pyran-2S-carboxylic acid (1R-methylcarbamoyl-2-naphthalen-2-yl-ethyl)-amide
  参考文献：
  名称：

  Novel tetrahydropyran-based peptidomimetics from a bioisosteric transformation of a tripeptide. Evidence of their activity at melanocortin receptors

  摘要：

  We have prepared novel peptidomimetics based on a 2,4,6-trisubstituted tetrahydropyran. This scaffold was constructed in an isosteric transformation using conceptual constraints imposed on a tripeptide moiety involving O-i'-C-1(+1)gamma and O-i'-Ni+2 formal cyclization modes. A series of regioselective transformations commencing with a substituted dihydropyran-4-one readily provided the required analogues. Specific tetrahydropyrane analogues modeled on PheArgTrp as a truncated version of the melanocortin receptor message sequence, showed activity at the melanocortin receptors MC4R and MC1R. Thus, the 2,4,6-trisubstituted tetrahydropyran scaffold has provided a potentially useful peptidomimetic lead, and conceptual cyclization of peptide moieties can offer a valuable design strategy in peptidomimetic research. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00274-8
• 作为产物：
  描述：

  [1R-(6R-cyano-4-oxo-tetrahydro-pyran-2R-yl)-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester 在 氢氧化钾 、 sodium hydride 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 29.0h， 生成 6R-[1R-tert-butoxycarbonylamino-2-(4-fluoro-phenyl)-ethyl]-4-cyanomethylene-tetrahydro-pyran-2S-carboxylic acid methyl ester
  参考文献：
  名称：

  Novel tetrahydropyran-based peptidomimetics from a bioisosteric transformation of a tripeptide. Evidence of their activity at melanocortin receptors

  摘要：

  We have prepared novel peptidomimetics based on a 2,4,6-trisubstituted tetrahydropyran. This scaffold was constructed in an isosteric transformation using conceptual constraints imposed on a tripeptide moiety involving O-i'-C-1(+1)gamma and O-i'-Ni+2 formal cyclization modes. A series of regioselective transformations commencing with a substituted dihydropyran-4-one readily provided the required analogues. Specific tetrahydropyrane analogues modeled on PheArgTrp as a truncated version of the melanocortin receptor message sequence, showed activity at the melanocortin receptors MC4R and MC1R. Thus, the 2,4,6-trisubstituted tetrahydropyran scaffold has provided a potentially useful peptidomimetic lead, and conceptual cyclization of peptide moieties can offer a valuable design strategy in peptidomimetic research. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00274-8