(R)-N-tert-butoxycarbonyl-2-(3'-formylethyl)proline | 221040-46-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-N-tert-butoxycarbonyl-2-(3'-formylethyl)proline
• 英文别名: (2R)-1-[(2-methylpropan-2-yl)oxycarbonyl]-2-(3-oxopropyl)pyrrolidine-2-carboxylic acid
• CAS: 221040-46-6
• 化学式: C₁₃H₂₁NO₅
• 分子量: 271.313
• InChiKey: XLIDSGUSSRFIKX-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  83.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-N-tert-butoxycarbonyl-2-(3'-formylethyl)proline 在 2-氯-1-甲基吡啶碘化物 、 碳酸氢钠 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 methyl <3'S-(3'α,6'α,8'aα)>-1-(tert-butoxycarbonyl)-5'-oxospiropiperidine>-3'-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Dopamine Receptor Modulating Activity of Spiro Bicyclic Peptidomimetics of l-Prolyl-l-leucyl-glycinamide

  摘要：

  In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of the thiazolidine and lactam ring systems would have on the ability of these systems to mimic the type-II beta-turn and (2) the effect that these structural perturbations would have on the ability of the peptidomimetics to modulate dopamine receptors. Through the use of the [H-3]spiroperidol/N-propylnorapomorphine (NPA) dopamine D-2 receptor competitive binding assay, 3 and 4, at a concentration of 100 nM, decreased the dissociation constant of the high-affinity state of the dopamine receptor for the agonist. These effects were observed when either Gpp(NH)p was absent or present and they were comparable to those produced by PLG at a concentration of 1 mu M. Peptidomimetics 3 and 4 also increased the percentage of D-2 receptors that existed in the high-affinity state. Even with Gpp(NH)p present, 3 and 4 were able to return the R-H/R-L ratios to values observed in the respective controls where Gpp(NH)p was absent. Furthermore, both peptidomimetics were able to attenuate the Gpp(NH)p-induced shift to the low-affinity state to a greater extent than PLG. Peptidomimetics 3 and 4 were evaluated in vivo as modulators of apomorphine-induced rotational behavior in the 6-hydroxydopamine-lesioned rat model of hemiparkinsonism, and each affected the rotational behavior in a bell-shaped dose-response relationship producing increases of 95 +/- 31% (0.01 mg/kg, ip) and 88 +/- 14% (0.001 mg/kg, ip), respectively. In comparison, the previously reported 5.5.5. spiro bicyclic lactam 2 increased rotational behavior by 25 +/- 11% (0.01 mg/kg, ip).

  DOI：

  10.1021/jm980525q
• 作为产物：
  描述：

  (S)-N-tert-butoxycarbonyl-2-(3'-butenyl)proline benzyl ester 在 palladium on activated charcoal sodium periodate 、 四氧化锇 、 氢气 作用下， 以 苯 为溶剂， 25.0 ℃ 、241.32 kPa 条件下， 反应 34.08h， 生成 (R)-N-tert-butoxycarbonyl-2-(3'-formylethyl)proline
  参考文献：
  名称：

  Design, Synthesis, and Dopamine Receptor Modulating Activity of Spiro Bicyclic Peptidomimetics of l-Prolyl-l-leucyl-glycinamide

  摘要：

  In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of the thiazolidine and lactam ring systems would have on the ability of these systems to mimic the type-II beta-turn and (2) the effect that these structural perturbations would have on the ability of the peptidomimetics to modulate dopamine receptors. Through the use of the [H-3]spiroperidol/N-propylnorapomorphine (NPA) dopamine D-2 receptor competitive binding assay, 3 and 4, at a concentration of 100 nM, decreased the dissociation constant of the high-affinity state of the dopamine receptor for the agonist. These effects were observed when either Gpp(NH)p was absent or present and they were comparable to those produced by PLG at a concentration of 1 mu M. Peptidomimetics 3 and 4 also increased the percentage of D-2 receptors that existed in the high-affinity state. Even with Gpp(NH)p present, 3 and 4 were able to return the R-H/R-L ratios to values observed in the respective controls where Gpp(NH)p was absent. Furthermore, both peptidomimetics were able to attenuate the Gpp(NH)p-induced shift to the low-affinity state to a greater extent than PLG. Peptidomimetics 3 and 4 were evaluated in vivo as modulators of apomorphine-induced rotational behavior in the 6-hydroxydopamine-lesioned rat model of hemiparkinsonism, and each affected the rotational behavior in a bell-shaped dose-response relationship producing increases of 95 +/- 31% (0.01 mg/kg, ip) and 88 +/- 14% (0.001 mg/kg, ip), respectively. In comparison, the previously reported 5.5.5. spiro bicyclic lactam 2 increased rotational behavior by 25 +/- 11% (0.01 mg/kg, ip).

  DOI：

  10.1021/jm980525q

文献信息

• Allosteric Modulation of the Dopamine D₂ Receptor by Pro-Leu-Gly-NH₂ Peptidomimetics Constrained in Either a Polyproline II Helix or a Type II β-Turn Conformation
  作者：Bhooma Raghavan、Kevin J. Skoblenick、Swapna Bhagwanth、Niran Argintaru、Ram K. Mishra、Rodney L. Johnson

  DOI：10.1021/jm801575w

  日期：2009.4.9

  Type II beta-turn mimics and polyproline II helix mimics based upon diasterecisomeric 5.6.5 spiro bicyclic scaffolds have provided two pairs of Pro-Leu-Gly-NH2 (PLG) peptidomimetics with contrasting dopamine receptor modulating activities. Compounds 1a and 3a were found to be positive allosteric modulators of the dopamine receptor, while the corresponding diastereoisomeric compounds 1b and 3b provided the first PLG peptidomimetics with the ability to decrease the binding of agonists to the dopamine receptor. The positive allosteric modulating activity of 3a supported the hypothesis that a polyproline II helix conformation is the bioactive conformation for the PLG analogue Pro-Pro-Pro-NH2. The results also show that a change in the bridgehead chirality of the 5.6.5 scaffold brings about opposite effects in terms of the modulation of the dopamine receptor.
• Myd88 Homodimerization Inhibitors
  申请人：Carminati Paolo

  公开号：US20080064643A1

  公开（公告）日：2008-03-13

  The present invention relates to peptidic and peptidomimetic compounds with the formula (X − )AA 1 -AA 2 -AA 3 -AA 4 -AA 5 -AA 6 -AA 7 in which the various groups are defined in the description here below, which mimic a particular protein portion of MyD88, preventing its homodimerisation and interfering with its interaction with the TIR domain. The present invention also provides procedures for the preparation of said compounds, pharmaceutical compositions containing them and their use as medicaments, particularly for the treatment of inflammatory and autoimmune diseases.
• Design, Synthesis, and Dopamine Receptor Modulating Activity of Spiro Bicyclic Peptidomimetics of <scp>l</scp>-Prolyl-<scp>l</scp>-leucyl-glycinamide
  作者：Ehab M. Khalil、William H. Ojala、Ashish Pradhan、Venugopalan D. Nair、William B. Gleason、Ram K. Mishra、Rodney L. Johnson

  DOI：10.1021/jm980525q

  日期：1999.2.1

  In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of the thiazolidine and lactam ring systems would have on the ability of these systems to mimic the type-II beta-turn and (2) the effect that these structural perturbations would have on the ability of the peptidomimetics to modulate dopamine receptors. Through the use of the [H-3]spiroperidol/N-propylnorapomorphine (NPA) dopamine D-2 receptor competitive binding assay, 3 and 4, at a concentration of 100 nM, decreased the dissociation constant of the high-affinity state of the dopamine receptor for the agonist. These effects were observed when either Gpp(NH)p was absent or present and they were comparable to those produced by PLG at a concentration of 1 mu M. Peptidomimetics 3 and 4 also increased the percentage of D-2 receptors that existed in the high-affinity state. Even with Gpp(NH)p present, 3 and 4 were able to return the R-H/R-L ratios to values observed in the respective controls where Gpp(NH)p was absent. Furthermore, both peptidomimetics were able to attenuate the Gpp(NH)p-induced shift to the low-affinity state to a greater extent than PLG. Peptidomimetics 3 and 4 were evaluated in vivo as modulators of apomorphine-induced rotational behavior in the 6-hydroxydopamine-lesioned rat model of hemiparkinsonism, and each affected the rotational behavior in a bell-shaped dose-response relationship producing increases of 95 +/- 31% (0.01 mg/kg, ip) and 88 +/- 14% (0.001 mg/kg, ip), respectively. In comparison, the previously reported 5.5.5. spiro bicyclic lactam 2 increased rotational behavior by 25 +/- 11% (0.01 mg/kg, ip).