ethyl 3-hydroxymethyl-4H-furo[3,2-b]pyrrole-5-carboxylate | 1007388-84-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡咯
• 英文名称: ethyl 3-hydroxymethyl-4H-furo[3,2-b]pyrrole-5-carboxylate
• 英文别名: ethyl 3-(hydroxymethyl)-4H-furo[3,2-b]pyrrole-5-carboxylate
• CAS: 1007388-84-2
• 化学式: C₁₀H₁₁NO₄
• 分子量: 209.202
• InChiKey: HDQJHQCDPZOMJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  75.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-hydroxymethyl-4H-furo[3,2-b]pyrrole-5-carboxylate 在 二氧化锰 二氯甲烷 、 silica gel 作用下， 以 二氯甲烷 为溶剂， 反应 16.5h， 以to give ethyl 3-formyl-4H-furo[3,2-b]pyrrole-5-carboxylate (1.0 g, 92%) as light yellow solid的产率得到ethyl 3-formyl-4H-furo[3,2-b]pyrrole-5-carboxylate
  参考文献：
  名称：

  Fused heterocyclic inhibitors of D-amino acid oxidase

  摘要：

  本发明提供了D-氨基酸氧化酶的新型抑制剂，以及包括该发明化合物的制药组合物。同时，还提供了治疗和预防神经系统疾病，如神经精神疾病和神经退行性疾病，以及疼痛、共济失调和惊厥的方法。该发明化合物具有以下一般结构：其中Q是从O、S、CR1和N中选择的成员，X和Y是独立选择自CR2、O、S、N和NR3的成员。

  公开号：

  US20080058395A1
• 作为产物：
  描述：

  2-azido-3-(4-hydroxymethyl-furan-2-yl)-propenoic acid ethyl ester 以 甲苯 为溶剂， 生成 ethyl 3-hydroxymethyl-4H-furo[3,2-b]pyrrole-5-carboxylate
  参考文献：
  名称：

  The discovery of fused pyrrole carboxylic acids as novel, potent d-amino acid oxidase (DAO) inhibitors

  摘要：

  The 'NMDA hypofunction hypothesis of schizophrenia' can be tested in a number of ways. DAO is the enzyme primarily responsible for the metabolism of d-serine, a co-agonist for the NMDA receptor. We identified novel DAO inhibitors, in particular, acid 1, which demonstrated moderate potency for DAO in vitro and ex vivo, and raised plasma d-serine levels after dosing ip to rats. In parallel, analogues were prepared to survey the SARs of 1.

  DOI：

  10.1016/j.bmcl.2008.04.020

文献信息

• FLUORO-SUBSTITUTED INHIBITORS OF D-AMINO ACID OXIDASE
  申请人：Heffernan L. R. Michele

  公开号：US20080004327A1

  公开（公告）日：2008-01-03

  This invention provides novel inhibitors of the enzyme D-amino acid oxidase as well as pharmaceutical compositions including the compounds of the invention. The invention also provides methods for the treatment and prevention of neurological disorders, such as neuropsychiatric and neurodegenerative diseases, as well as pain, ataxia and convulsion. The compounds of the invention have the general structure: wherein A is NH or S. Q is a member selected from CR 1 and N. X and Y are members independently selected from O, S, CR 2 , N and NH. R 1 , R 2 and R 4 are members independently selected from H and F, provided that at least one member selected from R 1 , R 2 and R 4 is F. R 6 is a member selected from O − X + and OH, wherein X + is a positive ion, which is a member selected from inorganic positive ions and organic positive ions.

  这项发明提供了D-氨基酸氧化酶的新型抑制剂，以及包括该发明中化合物的药物组合物。该发明还提供了用于治疗和预防神经系统疾病，如神经精神病和神经退行性疾病，以及疼痛、共济失调和抽搐的方法。该发明中的化合物具有一般结构：其中A为NH或S。Q是从CR1和N中选择的成员。X和Y分别是从O、S、CR2、N和NH中独立选择的成员。R1、R2和R4是从H和F中独立选择的成员，前提是至少选择R1、R2和R4中的一个成员为F。R6是从O−X+和OH中选择的成员，其中X+是正离子，从无机正离子和有机正离子中选择的成员。
• Fused heterocyclic inhibitors of D-amino acid oxidase
  申请人：Heffernan L. R. Michele

  公开号：US20080058395A1

  公开（公告）日：2008-03-06

  This invention provides novel inhibitors of the enzyme D-amino acid oxidase as well as pharmaceutical compositions including the compounds of the invention. Also provided are methods for the treatment and prevention of neurological disorders, such as neuropsychiatric and neurodegenerative diseases, as well as pain, ataxia and convulsion. The compounds of the invention have the general structure: wherein Q is a member selected from O, S, CR 1 and N, X and Y are members independently selected from CR 2 , O, S, N and NR 3 .

  本发明提供了D-氨基酸氧化酶的新型抑制剂，以及包括该发明化合物的制药组合物。同时，还提供了治疗和预防神经系统疾病，如神经精神疾病和神经退行性疾病，以及疼痛、共济失调和惊厥的方法。该发明化合物具有以下一般结构：其中Q是从O、S、CR1和N中选择的成员，X和Y是独立选择自CR2、O、S、N和NR3的成员。
• US7884124B2
  申请人：——

  公开号：US7884124B2

  公开（公告）日：2011-02-08
• The discovery of fused pyrrole carboxylic acids as novel, potent d-amino acid oxidase (DAO) inhibitors
  作者：Tim Sparey、Pravien Abeywickrema、Sarah Almond、Nick Brandon、Noel Byrne、Alister Campbell、Pete H. Hutson、Marlene Jacobson、Brian Jones、Sanjeev Munshi、Danette Pascarella、Andrew Pike、G. Sridhar Prasad、Nancy Sachs、Melanie Sakatis、Vinod Sardana、Shankar Venkatraman、Mary Beth Young

  DOI：10.1016/j.bmcl.2008.04.020

  日期：2008.6

  The 'NMDA hypofunction hypothesis of schizophrenia' can be tested in a number of ways. DAO is the enzyme primarily responsible for the metabolism of d-serine, a co-agonist for the NMDA receptor. We identified novel DAO inhibitors, in particular, acid 1, which demonstrated moderate potency for DAO in vitro and ex vivo, and raised plasma d-serine levels after dosing ip to rats. In parallel, analogues were prepared to survey the SARs of 1.
• Fluoro-substituted inhibitors of D-amino acid oxidase
  申请人：Sepracor Inc.

  公开号：US07884124B2

  公开（公告）日：2011-02-08

  This invention provides novel inhibitors of the enzyme D-amino acid oxidase as well as pharmaceutical compositions including the compounds of the invention. The invention also provides methods for the treatment and prevention of neurological disorders, such as neuropsychiatric and neurodegenerative diseases, as well as pain, ataxia and convulsion. The compounds of the invention have the general structure: wherein A is NH or S. Q is a member selected from CR1 and N. X and Y are members independently selected from O, S, CR2, N and NH. R1, R2 and R4 are members independently selected from H and F, provided that at least one member selected from R1, R2 and R4 is F. R6 is a member selected from O−X+ and OH, wherein X+ is a positive ion, which is a member selected from inorganic positive ions and organic positive ions.

  本发明提供了D-氨基酸氧化酶的新型抑制剂，以及包括本发明化合物的制药组合物。本发明还提供了用于治疗和预防神经系统疾病，如神经精神疾病和神经退行性疾病，以及疼痛、共济失调和抽搐的方法。本发明化合物具有以下一般结构： 其中A为NH或S。Q为选择自CR1和N的成员。X和Y是独立选择自O、S、CR2、N和NH的成员。R1、R2和R4是独立选择自H和F的成员，但至少选择自R1、R2和R4中的一个成员为F。R6为选择自O−X+和OH的成员，其中X+为正离子，其为选择自无机正离子和有机正离子的成员。