N-(benzyloxycarbonyl)-cis-4-cyano-D-proline ethyl ester | 130830-68-1

• 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: N-(benzyloxycarbonyl)-cis-4-cyano-D-proline ethyl ester
• 英文别名: 1-O-benzyl 2-O-ethyl (2R,4R)-4-cyanopyrrolidine-1,2-dicarboxylate
• CAS: 130830-68-1
• 化学式: C₁₆H₁₈N₂O₄
• 分子量: 302.33
• InChiKey: HWSAVXCMWJZFPX-UONOGXRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  79.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(benzyloxycarbonyl)-cis-4-cyano-D-proline ethyl ester 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 100.5h， 生成 Mosher amide of cis-4-carboxy-D-proline dimethyl ester
  参考文献：
  名称：

  Conformationally defined neurotransmitter analogs. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer

  摘要：

  In order to determine the conformational requirements for binding of L-glutamate to the proteins involved in the process of neurotransmission, rigid analogues containing an embedded glutamate moiety have been prepared. These ''conformer mimics'', the pyrrolidine-2,4-dicarboxylates 4, 7, 11, and 14, were synthesized from commercially available trans-4-hydroxy-L-proline and cis-4-hydroxy-D-proline, and then were tested for their ability to inhibit the high-affinity transport of [H-3]-L-glutamate into synaptosomes and to block the binding of radioligands to the NMDA (N-methyl-D-aspartate), KA (kainate), and QA (quisqualate) glutamate neurotransmitter receptor sites. While none of the four analogues binds effectively to the excitatory receptors, the L-trans-isomer 7 is a potent and selective competitive inhibitor of L-glutamate transport. These results delineate a specific structural/conformational preference for binding to the uptake system that is distinct from that required for binding to the NMDA, KA, and QA receptors.

  DOI：

  10.1021/jm00106a037
• 作为产物：
  描述：

  反式-1-苄基2-乙基4-羟基吡咯烷-1,2-二羧酸 在 吡啶 作用下， 以 氯仿 、 二甲基亚砜 为溶剂， 反应 168.0h， 生成 N-(benzyloxycarbonyl)-cis-4-cyano-D-proline ethyl ester
  参考文献：
  名称：

  Conformationally defined neurotransmitter analogs. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer

  摘要：

  In order to determine the conformational requirements for binding of L-glutamate to the proteins involved in the process of neurotransmission, rigid analogues containing an embedded glutamate moiety have been prepared. These ''conformer mimics'', the pyrrolidine-2,4-dicarboxylates 4, 7, 11, and 14, were synthesized from commercially available trans-4-hydroxy-L-proline and cis-4-hydroxy-D-proline, and then were tested for their ability to inhibit the high-affinity transport of [H-3]-L-glutamate into synaptosomes and to block the binding of radioligands to the NMDA (N-methyl-D-aspartate), KA (kainate), and QA (quisqualate) glutamate neurotransmitter receptor sites. While none of the four analogues binds effectively to the excitatory receptors, the L-trans-isomer 7 is a potent and selective competitive inhibitor of L-glutamate transport. These results delineate a specific structural/conformational preference for binding to the uptake system that is distinct from that required for binding to the NMDA, KA, and QA receptors.

  DOI：

  10.1021/jm00106a037

文献信息

• Method of inhibiting the transport of L-glutamate to treat CNS disorders
  申请人：The Regents of the University of California

  公开号：US05942537A1

  公开（公告）日：1999-08-24

  A method of inhibiting the transport of a neurotransmitter away from the synapse comprising contacting a neurotransmitter transporter with a compound having the structure ##STR1## wherein ##STR2## or CONHR.sup.3 in any combination and and wherein R.sup.2 =OR.sup.3, NR.sup.3.sub.2, alkyl, or substituted alkyl and R.sup.3 =alkyl or substituted alkyl.

  一种抑制神经递质从突触运输的方法，包括将具有以下结构的化合物与神经递质转运体接触：##STR1## 其中 ##STR2## 或 CONHR.sup.3 以任意组合方式出现，其中 R.sup.2 =OR.sup.3、NR.sup.3.sub.2、烷基或取代烷基，R.sup.3 =烷基或取代烷基。
• METHOD OF INHIBITING THE TRANSPORT OF L-GLUTAMATE
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：EP0497895A1

  公开（公告）日：1992-08-12
• US5942537A
  申请人：——

  公开号：US5942537A

  公开（公告）日：1999-08-24
• [EN] METHOD OF INHIBITING THE TRANSPORT OF L-GLUTAMATE
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：WO1991006536A1

  公开（公告）日：1991-05-16

  (EN) A method of inhibiting the transport of a neurotransmitter away from the synapse comprising contacting a neurotransmitter transporter with a compound having structure (I), wherein R1 = CO2H; -P(OH2); -SO3H; CO2R3; P(OR3)2; -SO3R; (a); or CONHR3 in any combination and wherein R2 = OR3, NR32, alkyl, or substituted alkyl and R3 = alkyl or substituted alkyl.(FR) Procédé d'inhibition du transport d'un neurotransmetteur en l'éloignant de la synapse, et consistant à mettre en contact un transporteur du neurotransmetteur avec un composé ayant la structure (I) dans laquelle R1 représente CO2H; -P(OH2); -SO3H; CO2R3; P(OR3)2; -SO3R; (a); ou CONHR3 dans n'importe quelle combinaison, et dans laquelle R2 représente OR3, NR32, alkyl, ou alkyl substitué et R3 représente alkyl ou alkyl substitué.
• Conformationally defined neurotransmitter analogs. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer
  作者：Richard J. Bridges、Mark S. Stanley、Michael W. Anderson、Carl W. Cotman、A. Richard Chamberlin

  DOI：10.1021/jm00106a037

  日期：1991.2

  In order to determine the conformational requirements for binding of L-glutamate to the proteins involved in the process of neurotransmission, rigid analogues containing an embedded glutamate moiety have been prepared. These ''conformer mimics'', the pyrrolidine-2,4-dicarboxylates 4, 7, 11, and 14, were synthesized from commercially available trans-4-hydroxy-L-proline and cis-4-hydroxy-D-proline, and then were tested for their ability to inhibit the high-affinity transport of [H-3]-L-glutamate into synaptosomes and to block the binding of radioligands to the NMDA (N-methyl-D-aspartate), KA (kainate), and QA (quisqualate) glutamate neurotransmitter receptor sites. While none of the four analogues binds effectively to the excitatory receptors, the L-trans-isomer 7 is a potent and selective competitive inhibitor of L-glutamate transport. These results delineate a specific structural/conformational preference for binding to the uptake system that is distinct from that required for binding to the NMDA, KA, and QA receptors.