ethyl 4-[(ethoxycarbonylmethyl)methylamino]-3-hydroxy-3-phenylpentanoate | 799247-84-0

• 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: ethyl 4-[(ethoxycarbonylmethyl)methylamino]-3-hydroxy-3-phenylpentanoate
• 英文别名: Ethyl 4-[(2-ethoxy-2-oxoethyl)-methylamino]-3-hydroxy-3-phenylpentanoate
• CAS: 799247-84-0
• 化学式: C₁₈H₂₇NO₅
• 分子量: 337.416
• InChiKey: BFFOQCRMQRTOMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-[(ethoxycarbonylmethyl)methylamino]-3-hydroxy-3-phenylpentanoate 在 吡啶 、 lithium hexamethyldisilazane 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 生成 Ethyl 1,6-dimethyl-3-oxo-5-phenyl-1,2,3,6-tetrahydropyridine-2-carboxylate
  参考文献：
  名称：

  Novel Secoergoline Derivatives Inhibit Both GABA and Glutamate Uptake in Rat Brain Homogenates:  Synthesis, in Vitro Pharmacology, and Modeling

  摘要：

  Three of twelve secoergoline derivatives (Z ethyl 4-[(ethoxycarbonylmethyl)methylamino]-2-methyl-3-phenylpent-2-enoate, 8; ethyl 1,6-dimethyl-3-oxo-5-phenyl-1,2,3,6-tetrahydropyridine-2-carboxylate, 9; Z methyl 4-[(methoxycarbonylmethyl)methylamino)-2-methyl-3-phenylpent-2-enoate, 11), containing bioisosteric sequences of GABA and Glu, inhibited both GABA and Glu transport through cerebrocortical membranes specifically. Compounds 8, 9, and 11 appeared to be equipotent inhibitors of GABA and Glu transport with IC50 values between 270 and 1100,muM, whereas derivatives 1-7, 10, and 12 were without effects. In the presence of GABA and Glu transport-specific nontransportable inhibitors, inhibition of GABA and Glu transport by 8, 9, and 11 proceeded in two phases. The two phases of inhibition were characterized by IC50 values between 4 and 180 nM and 360-1020 muM and different selectivity sequences. These findings may indicate the existence of some mechanism possibly mediated by a previously unrecognized GABA-Glu transporter. Derivatives with the cis, but not the trans configuration of bulky ester groups (8 vs 7 and 11 vs 12) showed significant inhibitory effect (IC50 values of 270,muM vs >>1000 muM and 1100 muM vs >>1000 muM on GABA transport, respectively). The cis-trans selectivity can be explained by docking these secoergolines in a three-dimensional model of the second and third transmembrane helices of GABA transporter type 1.

  DOI：

  10.1021/jm040809c
• 作为产物：
  描述：

  苯丙酮,2-氨基-,盐酸盐 在 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.42h， 生成 ethyl 4-[(ethoxycarbonylmethyl)methylamino]-3-hydroxy-3-phenylpentanoate
  参考文献：
  名称：

  Novel Secoergoline Derivatives Inhibit Both GABA and Glutamate Uptake in Rat Brain Homogenates:  Synthesis, in Vitro Pharmacology, and Modeling

  摘要：

  Three of twelve secoergoline derivatives (Z ethyl 4-[(ethoxycarbonylmethyl)methylamino]-2-methyl-3-phenylpent-2-enoate, 8; ethyl 1,6-dimethyl-3-oxo-5-phenyl-1,2,3,6-tetrahydropyridine-2-carboxylate, 9; Z methyl 4-[(methoxycarbonylmethyl)methylamino)-2-methyl-3-phenylpent-2-enoate, 11), containing bioisosteric sequences of GABA and Glu, inhibited both GABA and Glu transport through cerebrocortical membranes specifically. Compounds 8, 9, and 11 appeared to be equipotent inhibitors of GABA and Glu transport with IC50 values between 270 and 1100,muM, whereas derivatives 1-7, 10, and 12 were without effects. In the presence of GABA and Glu transport-specific nontransportable inhibitors, inhibition of GABA and Glu transport by 8, 9, and 11 proceeded in two phases. The two phases of inhibition were characterized by IC50 values between 4 and 180 nM and 360-1020 muM and different selectivity sequences. These findings may indicate the existence of some mechanism possibly mediated by a previously unrecognized GABA-Glu transporter. Derivatives with the cis, but not the trans configuration of bulky ester groups (8 vs 7 and 11 vs 12) showed significant inhibitory effect (IC50 values of 270,muM vs >>1000 muM and 1100 muM vs >>1000 muM on GABA transport, respectively). The cis-trans selectivity can be explained by docking these secoergolines in a three-dimensional model of the second and third transmembrane helices of GABA transporter type 1.

  DOI：

  10.1021/jm040809c

文献信息

• Novel <i>Seco</i>ergoline Derivatives Inhibit Both GABA and Glutamate Uptake in Rat Brain Homogenates:  Synthesis, in Vitro Pharmacology, and Modeling
  作者：László Héja、Ilona Kovács、Éva Szárics、Mária Incze、Eszter Temesváriné-Major、Gábor Dörnyei、Mária Peredy-Kajtár、Eszter Gács-Baitz、Csaba Szántay、Julianna Kardos

  DOI：10.1021/jm040809c

  日期：2004.11.1

  Three of twelve secoergoline derivatives (Z ethyl 4-[(ethoxycarbonylmethyl)methylamino]-2-methyl-3-phenylpent-2-enoate, 8; ethyl 1,6-dimethyl-3-oxo-5-phenyl-1,2,3,6-tetrahydropyridine-2-carboxylate, 9; Z methyl 4-[(methoxycarbonylmethyl)methylamino)-2-methyl-3-phenylpent-2-enoate, 11), containing bioisosteric sequences of GABA and Glu, inhibited both GABA and Glu transport through cerebrocortical membranes specifically. Compounds 8, 9, and 11 appeared to be equipotent inhibitors of GABA and Glu transport with IC50 values between 270 and 1100,muM, whereas derivatives 1-7, 10, and 12 were without effects. In the presence of GABA and Glu transport-specific nontransportable inhibitors, inhibition of GABA and Glu transport by 8, 9, and 11 proceeded in two phases. The two phases of inhibition were characterized by IC50 values between 4 and 180 nM and 360-1020 muM and different selectivity sequences. These findings may indicate the existence of some mechanism possibly mediated by a previously unrecognized GABA-Glu transporter. Derivatives with the cis, but not the trans configuration of bulky ester groups (8 vs 7 and 11 vs 12) showed significant inhibitory effect (IC50 values of 270,muM vs >>1000 muM and 1100 muM vs >>1000 muM on GABA transport, respectively). The cis-trans selectivity can be explained by docking these secoergolines in a three-dimensional model of the second and third transmembrane helices of GABA transporter type 1.