ethyl (2S,1'S,2'R,3'R)-N-(tert-butoxycarbonyl)-2-(2'-ethoxycarbonyl-3'-hydroxymethylcyclopropyl) glycinate | 312912-64-4

• 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 (2S,1'S,2'R,3'R)-N-(tert-butoxycarbonyl)-2-(2'-ethoxycarbonyl-3'-hydroxymethylcyclopropyl) glycinate
• 英文别名: ethyl (1R,2S,3R)-2-[(1S)-2-ethoxy-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxoethyl]-3-(hydroxymethyl)cyclopropane-1-carboxylate
• CAS: 312912-64-4
• 化学式: C₁₆H₂₇NO₇
• 分子量: 345.393
• InChiKey: WMZVNEVDZISIJS-RHYQMDGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl (2S,1'S,2'R,3'R)-N-(tert-butoxycarbonyl)-2-(2'-ethoxycarbonyl-3'-hydroxymethylcyclopropyl) glycinate 在 ruthenium trichloride 、 sodium periodate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氯化碳 、 二氯甲烷 为溶剂， 生成 (1R,2R,3R)-3-((S)-tert-Butoxycarbonylamino-ethoxycarbonyl-methyl)-cyclopropane-1,2-dicarboxylic acid 1-(2,5-dioxo-pyrrolidin-1-yl) ester 2-ethyl ester
  参考文献：
  名称：

  (2S,1′S,2′R,3′R)-2(2′-Carboxy-3′-hydroxymethylcyclopropyl)glycine-[3H], a potent and selective radioligand for labeling group 2 and 3 metabotropic glutamate receptors

  摘要：

  We report herein the synthesis of the tritium labeled isotopomer of 1 and its use as a radioligand to label mGlu8 receptors in rat forebrain membranes as well as cloned human recombinant mGlu receptors. [H-3]-1 was synthesized by the NaBT4 reduction of an activated analog of 5. [H-3]-1 bound appreciably to recombinant human mGlu2, mGlu3 and mGlu8 receptors and to rat forebrain membranes and was displaced by L-glutamate and L-(+)-2 amino-4-phosphonobutyric acid. The results indicate that [H-3]-1 should be a useful ligand for the study of mGluR2, 3, and 8 receptors in cloned cell lines and possibly brain tissue. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.10.093
• 作为产物：
  描述：

  methyl (1S,2R,3S)-2-benzyloxymethyl-3-hydroxymethylcyclopropane carboxylate 在 palladium on activated charcoal 咪唑 、 lead(IV) acetate 、 四丙基高钌酸铵 、 四丁基氟化铵 、 氢气 、 双(三甲基硅烷基)氨基钾 、 碳酸氢钠 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 32.84h， 生成 ethyl (2S,1'S,2'R,3'R)-N-(tert-butoxycarbonyl)-2-(2'-ethoxycarbonyl-3'-hydroxymethylcyclopropyl) glycinate
  参考文献：
  名称：

  (2S,1‘S,2‘R,3‘R)-2-(2‘-Carboxy-3‘-hydroxymethylcyclopropyl) Glycine Is a Highly Potent Group 2 and 3 Metabotropic Glutamate Receptor Agonist with Oral Activity

  摘要：

  The asymmetric synthesis and biological activity of (2S,1'S,2R,3R)-2-(2 -carboxy-3'-hydroxy-methylcyclopropyl) glycine ((+)-3) is described. This novel C-3' substituted carboxy cyclopropyl glycine is a highly potent group 2 and group 3 mGluR agonist that has proven to be orally active in both fear potentiated startle (animal model for anxiety) and PCP-induced motor activation (animal model for psychosis) assays in rats.

  DOI：

  10.1021/jm030967o

文献信息

• Excitatory amino acid receptor modulators
  申请人：Eli Lilly and Company

  公开号：US06498180B1

  公开（公告）日：2002-12-24

  Compounds of formula (I) in which R1 is halo-C1-10 alkyl; halo-C2-10 alkenyl; or (CH2)nY in which n is 1 or 2 and Y is OH, CN, N3, OR3, SH, S(O)pR4, S(O)3H, NH2, NHR5, NR6R7, NHCOR8, NO2, CO2H, CONHR9, 1H-tetrazol-5-yl, 5-phenyltetrazol-2-yl or PO3H2; R3, R5, R6, R7, R8 and R9 are each selected independently from C1-4 alkyl, aryl and aryl-C1-4 alkyl; R4 is selected from C1-4 alkyl, aryl, aryl-C1-4 alkyl, and 1H-tetrazol-5-yl, carboxy-(1-4C)alkyl and 1H-tetrazol-5-yl-C1-4 alkyl; and p is 0, 1, 2 or 3; or a salt or ester thereof, provided that R1 is not methoxymethyl, modulate metabotropic glutamate receptor function and are useful in treating disorders of the central nervous system.

  式(I)中R1为卤代-C1-10烷基；卤代-C2-10烯基；或(CH2)nY，其中n为1或2，Y为OH，CN，N3，OR3，SH，S(O)pR4，S(O)3H，NH2，NHR5，NR6R7，NHCOR8，NO2，CO2H，CONHR9，1H-四唑-5-基，5-苯基四唑-2-基或PO3H2；R3，R5，R6，R7，R8和R9各自独立地选自C1-4烷基，芳基和芳基-C1-4烷基；R4选自C1-4烷基，芳基，芳基-C1-4烷基和1H-四唑-5-基，羧基-(1-4C)烷基和1H-四唑-5-基-C1-4烷基；p为0，1，2或3；或其盐或酯，前提是R1不是甲氧甲基，调节代谢型谷氨酸受体功能，并且在治疗中枢神经系统疾病中有用。
• (2<i>S</i>,1‘<i>S</i>,2‘<i>R</i>,3‘<i>R</i>)-2-(2‘-Carboxy-3‘-hydroxymethylcyclopropyl) Glycine Is a Highly Potent Group 2 and 3 Metabotropic Glutamate Receptor Agonist with Oral Activity
  作者：Iván Collado、Concepción Pedregal、Ana Belén Bueno、Alicia Marcos、Rosario González、Jaime Blanco-Urgoiti、Javier Pérez-Castells、Darryle D. Schoepp、Rebecca A. Wright、Bryan G. Johnson、Ann E. Kingston、Eric D. Moher、David W. Hoard、Kelly I. Griffey、Joseph P. Tizzano

  DOI：10.1021/jm030967o

  日期：2004.1.1

  The asymmetric synthesis and biological activity of (2S,1'S,2R,3R)-2-(2 -carboxy-3'-hydroxy-methylcyclopropyl) glycine ((+)-3) is described. This novel C-3' substituted carboxy cyclopropyl glycine is a highly potent group 2 and group 3 mGluR agonist that has proven to be orally active in both fear potentiated startle (animal model for anxiety) and PCP-induced motor activation (animal model for psychosis) assays in rats.
• (2S,1′S,2′R,3′R)-2(2′-Carboxy-3′-hydroxymethylcyclopropyl)glycine-[3H], a potent and selective radioligand for labeling group 2 and 3 metabotropic glutamate receptors
  作者：William J. Wheeler、Dean K. Clodfelter、Palaniappan Kulanthaivel、Concepcion Pedregal、Eli A. Stoddard、Rebecca A. Wright、Darryle D. Schoepp

  DOI：10.1016/j.bmcl.2004.10.093

  日期：2005.1

  We report herein the synthesis of the tritium labeled isotopomer of 1 and its use as a radioligand to label mGlu8 receptors in rat forebrain membranes as well as cloned human recombinant mGlu receptors. [H-3]-1 was synthesized by the NaBT4 reduction of an activated analog of 5. [H-3]-1 bound appreciably to recombinant human mGlu2, mGlu3 and mGlu8 receptors and to rat forebrain membranes and was displaced by L-glutamate and L-(+)-2 amino-4-phosphonobutyric acid. The results indicate that [H-3]-1 should be a useful ligand for the study of mGluR2, 3, and 8 receptors in cloned cell lines and possibly brain tissue. (C) 2004 Elsevier Ltd. All rights reserved.