N-(benzyloxycarbonyl)-cis-4-(tosyloxy)-D-proline ethyl ester | 130830-63-6

• 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: N-(benzyloxycarbonyl)-cis-4-(tosyloxy)-D-proline ethyl ester
• 英文别名: (2R,4R)-N-benzyloxycarbonyl-2-ethoxycarbonyl-4-(p-toluenesulfonyloxy)-pyrrolidine；(2R,4R)-1-Benzyl 2-ethyl 4-(tosyloxy)pyrrolidine-1,2-dicarboxylate；1-O-benzyl 2-O-ethyl (2R,4R)-4-(4-methylphenyl)sulfonyloxypyrrolidine-1,2-dicarboxylate
• CAS: 130830-63-6
• 化学式: C₂₂H₂₅NO₇S
• 分子量: 447.509
• InChiKey: VJWIBONSIXXNGR-UYAOXDASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(benzyloxycarbonyl)-cis-4-(tosyloxy)-D-proline ethyl ester 在 盐酸 作用下， 以 二甲基亚砜 为溶剂， 反应 100.0h， 生成 N-(benzyloxycarbonyl)-trans-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：

  顺式-4-羟基-D-脯氨酸 在 吡啶 、 碳酸氢钠 、 对甲苯磺酸 作用下， 以 氯仿 、 水 、 甲苯 为溶剂， 反应 200.5h， 生成 N-(benzyloxycarbonyl)-cis-4-(tosyloxy)-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

• The relationship between physicochemical properties, In vitro activity and pharmacokinetic profiles of analogues of diamine-Containing efflux pump inhibitors
  作者：William J. Watkins、Yakira Landaverry、Roger Léger、Renée Litman、Thomas E. Renau、Nicole Williams、Rose Yen、Jason Z. Zhang、Suzanne Chamberland、Deidre Madsen、David Griffith、Vrushali Tembe、Keith Huie、Michael N. Dudley

  DOI：10.1016/j.bmcl.2003.07.030

  日期：2003.12

  diamine-containing efflux pump inhibitors with respect to in vitro potentiation activity, in vivo stability and acute toxicity, we addressed the question of how to control the pharmacokinetic properties of the series. Upon intravenous administration in the rat, tissue levels of MC-04,124 (the lead compound) were high and prolonged compared to those in the serum. The lipophilicity and basicity of analogues of this

  在体外增强活性，体内稳定性和急性毒性方面优化含二胺的外排泵抑制剂后，我们解决了如何控制该系列药代动力学特性的问题。在大鼠中静脉内给药后，与血清中的组织水平相比，MC-04,124（先导化合物）的组织水平较高且持续时间较长。系统地改变了该化合物类似物的亲脂性和碱性，并探讨了其对药效和药代动力学的影响。在任何检查的活性类似物中，组织与血清中药物水平的比率均未显着降低。
• Benzamide derivatives
  申请人：TEIKOKU CHEMICAL INDUSTRY CO., LTD.

  公开号：EP0481756A2

  公开（公告）日：1992-04-22

  A benzamide derivative represented by the formula: having a promoting activity of gastrointestinal tract and pharmacentical composition containing the same.

  一种由式 具有促进胃肠道活性的苯甲酰胺衍生物和含有该衍生物的药物组合物。
• BRIDGES, RICHARD J.;STANLEY, MARK S.;ANDERSON, MICHAEL W.;COTMAN, CARL W.+, J. MED. CHEM., 34,(1991) N, C. 717-725
  作者：BRIDGES, RICHARD J.、STANLEY, MARK S.、ANDERSON, MICHAEL W.、COTMAN, CARL W.+

  DOI：——

  日期：——
• 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
• US5143935A
  申请人：——

  公开号：US5143935A

  公开（公告）日：1992-09-01