2-oxo-α-(2-propenyl)-1-pyrrolidineacetic acid methylester | 136294-30-9

• 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: 2-oxo-α-(2-propenyl)-1-pyrrolidineacetic acid methylester
• 英文别名: methyl 2-(2-oxopyrrolidin-1-yl)pent-4-enoate
• CAS: 136294-30-9
• 化学式: C₁₀H₁₅NO₃
• 分子量: 197.234
• InChiKey: KPHFHECGSJAGMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-oxo-α-(2-propenyl)-1-pyrrolidineacetic acid methylester 在 lithium hydroxide 、 水 、 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以81%的产率得到2-(2-Oxopyrrolidin-1-yl)pent4-enoic acid
  参考文献：
  名称：

  Macrocyclic diaminopropanes as beta-secretase inhibitors

  摘要：

  提供了一系列新型的大环二胺丙烷化合物，其化学式为（I）或其立体异构体；或其药学上可接受的盐，其中R1、R2、R4、R5、n、L、Z等如本文定义，它们的药物组合物和使用方法。这些新型化合物抑制β-分泌酶对淀粉样前体蛋白（APP）的加工，更具体地说，抑制Aβ肽的产生。本公开涉及用于治疗与β-淀粉样蛋白产生相关的神经疾病的化合物，如阿尔茨海默病和其他受抗淀粉样活性影响的疾病。

  公开号：

  US20070037868A1
• 作为产物：
  描述：

  α-acetoxy-2-oxo-5-(2-propenyl)-pyrrolidineacetic acid methyl ester 在 三乙基硅烷 、 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 以30%的产率得到2-oxo-α-(2-propenyl)-1-pyrrolidineacetic acid methylester
  参考文献：
  名称：

  Tin tetrachloride-induced π-cyclizations of glycine cation equivalents to substituted pipecolic acid derivatives

  摘要：

  Cationic pi-cyclization reactions of N-(3-alkenyl)-N-(methoxycarbonyl)acetoxyglycine esters induced by tin tetrachloride in dichloromethane are described. Reactions started and quenched with water at -78-degrees-C mainly yield cis-4-hydroxypipecolic esters, whereas reactions quenched after warm-up to room temperature provide trans-4-chloropipecolic esters as major products. A mechanistic scheme is advanced which adequately explains these results. The essentials are a rapid cationic aza-Cope equilibrium of the incipient iminium cation, and participation of the ester moiety through formation of a relatively stable bicyclic dioxycarbenium cation as pivotal intermediate.

  DOI：

  10.1016/s0040-4020(01)86443-7

文献信息

• US7338974B2
  申请人：——

  公开号：US7338974B2

  公开（公告）日：2008-03-04
• [EN] MACROCYCLIC DIAMINOPROPANES AS BETA-SECRETASE INHIBITORS<br/>[FR] DIAMINOPROPANES MACROCYCLIQUES COMME INHIBITEURS DE LA BETA-SECRETASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2007021793A1

  公开（公告）日：2007-02-22

  [EN] There is provided a series of novel macrocyclic diaminopropanes of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R₁, R₂, R₄, R₅, n, L, and Z are defined in claim 1 their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein (APP) by ß-secretase and, more specifically, inhibit the production of Aß-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to ß-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.
  [FR] L'invention concerne un groupe de nouveaux diaminopropanes macrocycliques de formule (I) ou un stéréoisomère; ou n un sel de celui-ci acceptable sur le plan pharmaceutique ; formule dans laquelle R₁, R₂, R₄, R₅, n, L, et Z sont définis dans la revendication (1), ainsi que les compositions pharmaceutiques et les procédés d'utilisation correspondants. Ces nouveaux composés inhibent la transformation de la protéine précurseur amyloïde (APP) par la ß-sécrétase et, plus spécifiquement, inhibent la production du peptide ß-amyloïde. Par ailleurs, l'invention concerne des composés utilisés dans le traitement des troubles neurologiques liés à la production de ß-amyloïde, tels que la maladie d'Alzheimer et d'autres états pathologiques affectés par l'activité anti-amyloïde.
• Tin tetrachloride-induced π-cyclizations of glycine cation equivalents to substituted pipecolic acid derivatives
  作者：Peter M Esch、Ilona M Boska、Henk Hiemstra、Richard F de Boer、W.Nico Speckamp

  DOI：10.1016/s0040-4020(01)86443-7

  日期：1991.1

  Cationic pi-cyclization reactions of N-(3-alkenyl)-N-(methoxycarbonyl)acetoxyglycine esters induced by tin tetrachloride in dichloromethane are described. Reactions started and quenched with water at -78-degrees-C mainly yield cis-4-hydroxypipecolic esters, whereas reactions quenched after warm-up to room temperature provide trans-4-chloropipecolic esters as major products. A mechanistic scheme is advanced which adequately explains these results. The essentials are a rapid cationic aza-Cope equilibrium of the incipient iminium cation, and participation of the ester moiety through formation of a relatively stable bicyclic dioxycarbenium cation as pivotal intermediate.
• Macrocyclic diaminopropanes as beta-secretase inhibitors
  申请人：Marcin R. Lawrence

  公开号：US20070037868A1

  公开（公告）日：2007-02-15

  There is provided a series of novel macrocyclic diaminopropanes of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 4 , R 5 , n, L, Z, and as defined herein, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein (APP) by β-secretase and, more specifically, inhibit the production of Aβ-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to β-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.

  提供了一系列新型的大环二胺丙烷化合物，其化学式为（I）或其立体异构体；或其药学上可接受的盐，其中R1、R2、R4、R5、n、L、Z等如本文定义，它们的药物组合物和使用方法。这些新型化合物抑制β-分泌酶对淀粉样前体蛋白（APP）的加工，更具体地说，抑制Aβ肽的产生。本公开涉及用于治疗与β-淀粉样蛋白产生相关的神经疾病的化合物，如阿尔茨海默病和其他受抗淀粉样活性影响的疾病。