(2R,4'R,8A'R)-1-叔丁基4'-甲基6'-氧代六氢螺[吡咯烷-2,7'-吡咯并[2,1- | 221040-37-5

• 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: (2R,4'R,8A'R)-1-叔丁基4'-甲基6'-氧代六氢螺[吡咯烷-2,7'-吡咯并[2,1-
• 英文名称: methyl <4'R-(4'α,7'α,8'aα)>-1-(tert-butoxycarbonyl)tetrahydro-6'-oxospiro-thiazine>-4'-carboxylate
• 英文别名: (2R,4'R,8a'R)-6'-oxotetrahydro-1H,2'H-spiro[pyrrolidine-2,7'-pyrrolo[2,1-b][1,3]thiazine]-1,4'-dicarboxylic acid 1-tert-butyl 4'-methyl ester；Spiro[pyrrolidine-2,7'(6'H)-[2H]pyrrolo[2,1-b][1,3]thiazine]-1,4'-dicarboxylic acid, tetrahydro-6'-oxo-, 1-(1,1-dimethylethyl) 4'-methyl ester, (2R,4'R,8'aR)-；1-O'-tert-butyl 4-O-methyl (4R,7R,8aR)-6-oxospiro[3,4,8,8a-tetrahydro-2H-pyrrolo[2,1-b][1,3]thiazine-7,2'-pyrrolidine]-1',4-dicarboxylate
• CAS: 221040-37-5
• 化学式: C₁₇H₂₆N₂O₅S
• 分子量: 370.47
• InChiKey: NPBOEBYKTZRFHL-PSTGCABASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,4'R,8A'R)-1-叔丁基4'-甲基6'-氧代六氢螺[吡咯烷-2,7'-吡咯并[2,1- 在 盐酸 、 氨 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 76.0h， 生成 <4'R-(4'α,7'α,8'aα)>-1-<<1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl>carbonyl>tetrahydro-6'-oxospirothiazine>-4'-carboxamide
  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：

  (R)-2-烯丙基吡咯烷-2-羧酸 在 sodium hydroxide 、 sodium periodate 、 四氧化锇 、 四甲基氢氧化铵 、 水 、 三乙胺 作用下， 以 甲醇 、 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 125.08h， 生成 (2R,4'R,8A'R)-1-叔丁基4'-甲基6'-氧代六氢螺[吡咯烷-2,7'-吡咯并[2,1-
  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

• 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).