2-(3-丁烯基)-L-脯氨酸 | 178752-81-3

• 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
• 中文名称: 2-(3-丁烯基)-L-脯氨酸
• 中文别名: L-脯氨酸,2-(3-丁烯基)-
• 英文名称: (S)-2-(3'-butenyl)proline
• 英文别名: (S)-2-but-3-en-1-ylproline；L-Proline, 2-(3-buten-1-yl)-；(2S)-2-but-3-enylpyrrolidine-2-carboxylic acid
• CAS: 178752-81-3
• 化学式: C₉H₁₅NO₂
• 分子量: 169.224
• InChiKey: OFHNEECFOQNBAB-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-丁烯基)-L-脯氨酸 在 palladium on activated charcoal sodium periodate 、 四氧化锇 、 四甲基氢氧化铵 、 氢气 、 碳酸氢钠 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙醇 、 乙腈 、 苯 为溶剂， 25.0 ℃ 、241.32 kPa 条件下， 反应 135.58h， 生成 (2RS,4S)-2-<<2'-(R)-N-(tert-butoxycarbonyl)-2'-carboxypyrrolidinyl>ethyl>thiazolidine-4-carboxylic acid methyl ester
  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：

  (2R,5S)-5-(3'-butenyl)-2-tert-butyl-1-aza-3-oxabicyclo-<3.3.0>-octan-4-one 在 60 Angstroem silica gel 、 水 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以94%的产率得到2-(3-丁烯基)-L-脯氨酸
  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

• An efficient and high yield method for the N-tert-butoxycarbonyl protection of sterically hindered amino acids
  作者：Ehab M. Khalil、Nalin L. Subasinghe、Rodney L. Johnson

  DOI：10.1016/0040-4039(96)00589-8

  日期：1996.5

  An improved method for the N-tert-butoxycarbonyl protection of the amino functionality of α-alkylated prolines and other sterically hindered α,α-disubstituted amino acids has been developed in which the lipophilic base tetramethylammonium hydroxide is used to solubilize the otherwise insoluble zwitterionic amino acid in acetonitrile, thereby obviating the need for an aqueous medium.

  用于一种改进的方法ñ -叔的α -烷基化的脯氨酸和其它空间的氨基官能团保护丁氧羰受阻α，α-二取代的氨基酸已经被开发，其中所述亲脂性基氢氧化四甲铵被用于溶解，否则不溶性两性离子氨基乙腈中的乙酸，从而消除了对水性介质的需求。
• 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 In Vitro Activity of Peptidomimetic Inhibitors of Myeloid Differentiation Factor 88
  作者：Nicola Fantò、Grazia Gallo、Andrea Ciacci、Mauro Semproni、Davide Vignola、Marco Quaglia、Valentina Bombardi、Domenico Mastroianni、M. Pia Zibella、Giancarlo Basile、Marica Sassano、Vito Ruggiero、Rita De Santis、Paolo Carminati

  DOI：10.1021/jm070723u

  日期：2008.3.13

  We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide Ac-RDVLPGT-NH(2), belonging to the Toll/IL-1 receptor (TIR) domain of the adaptor protein MyD88 and effective in inhibiting its homodimerization. The ability of the peptidomimetics to inhibit protein-protein interaction was assessed by yeast 2-hybrid assay and further validated in a mammalian cell system by evaluating the inhibition of NF-kappa B activation, a transcription factor downstream of MyD88 signaling pathway that allows production of essential effector molecules for immune and inflammatory responses.
• 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).