3-溴-4H-噻吩并[3,2-b]吡咯-5-羧酸乙酯 | 332099-35-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡咯类
• 中文名称: 3-溴-4H-噻吩并[3,2-b]吡咯-5-羧酸乙酯
• 中文别名: 乙基3-溴-4H-噻吩并[3,2-B]吡咯-5-羧酸甲酯
• 英文名称: ethyl 3-bromo-4H-thieno[3,2-b]pyrrole-5-carboxylate
• 英文别名: Ethyl 4H-3-bromothieno[3,2-b]pyrrole-5-carboxylate；3-Bromo-4H-thieno[3,2-b]pyrrole-5-carboxylic acid ethyl ester；3-bromothieno[3,2-b]pyrrole-5-carboxylic acid ethyl ester
• CAS: 332099-35-1
• 化学式: C₉H₈BrNO₂S
• 分子量: 274.138
• InChiKey: KSONMHNRMJQMFE-UHFFFAOYSA-N

物化性质

• 沸点：
  398.8±37.0 °C(Predicted)
• 密度：
  1.692±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  70.3
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  3-溴-4H-噻吩并[3,2-b]吡咯-5-羧酸乙酯 在 吡啶 、 copper(l) iodide 、 copper diacetate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 25.0h， 生成 ethyl 4-(4-fluorophenyl)-3-(trifluoromethyl)-4H-thieno[3,2-b]pyrrole-5-carboxylate
  参考文献：
  名称：

  Synthetic studies of centromere-associated protein-E (CENP-E) inhibitors: 1.Exploration of fused bicyclic core scaffolds using electrostatic potential map

  摘要：

  Centromere-associated protein-E (CENP-E), a mitotic kinesin that plays an important role in mitotic progression, is an attractive target for cancer therapeutic drugs. For the purpose of developing novel CENP-E inhibitors as cancer therapeutics, we investigated a fused bicyclic compound identified by high throughput screening, 4-oxo-4,5-dihydrothieno[3,4-clpyridine-6-carboxamide la. Based on this scaffold, we designed inhibitors for efficient binding at the L5 site in CENP-E utilizing homology modeling as well as electrostatic potential map (EPM) analysis to enhance CENP-E inhibitory activity. This resulted in a new lead, 5-bromoimidazo[l,2-a]pyridine 7, which showed potent CENP-E enzyme inhibition (IC50: 50 nM) and cellular activity with accumulation of phosphorylated histone H3 in HeLa cells. Our homology model and EPM analysis proved to be useful tools for the rational design of CENP-E inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.067
• 作为产物：
  描述：

  4-溴-2-噻吩甲醛 在 sodium ethanolate 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 为溶剂， 反应 4.5h， 生成 3-溴-4H-噻吩并[3,2-b]吡咯-5-羧酸乙酯
  参考文献：
  名称：

  Synthetic studies of centromere-associated protein-E (CENP-E) inhibitors: 1.Exploration of fused bicyclic core scaffolds using electrostatic potential map

  摘要：

  Centromere-associated protein-E (CENP-E), a mitotic kinesin that plays an important role in mitotic progression, is an attractive target for cancer therapeutic drugs. For the purpose of developing novel CENP-E inhibitors as cancer therapeutics, we investigated a fused bicyclic compound identified by high throughput screening, 4-oxo-4,5-dihydrothieno[3,4-clpyridine-6-carboxamide la. Based on this scaffold, we designed inhibitors for efficient binding at the L5 site in CENP-E utilizing homology modeling as well as electrostatic potential map (EPM) analysis to enhance CENP-E inhibitory activity. This resulted in a new lead, 5-bromoimidazo[l,2-a]pyridine 7, which showed potent CENP-E enzyme inhibition (IC50: 50 nM) and cellular activity with accumulation of phosphorylated histone H3 in HeLa cells. Our homology model and EPM analysis proved to be useful tools for the rational design of CENP-E inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.067

文献信息

• Use of glycogen phosphorylase inhibitors
  申请人：——

  公开号：US20030004162A1

  公开（公告）日：2003-01-02

  The invention provides methods of treating prophylactically an individual in whom Type 2 diabetes mellitus has not yet presented, but in whom there is an increased risk of developing such condition, which methods comprise administering to an individual in need thereof an effective amount of a glycogen phosphorylase inhibitor; effective amounts of a glycogen phosphorylase inhibitor and a non-glycogen phosphorylase inhibiting anti-diabetic agent; or effective amounts of a glycogen phosphorylase inhibitor and an anti-obesity agent. The invention further provides methods of treating prophylactically an individual in whom Type 2 diabetes mellitus has not yet presented, but in whom there is an increased risk of developing such condition, which methods comprise administering to an individual in need thereof a pharmaceutical composition comprising effective amounts of a glycogen phosphorylase inhibitor and a non-glycogen phosphorylase inhibiting anti-diabetic agent; or effective amounts of a glycogen phosphorylase inhibitor and an anti-obesity agent.

  本发明提供了一种预防性地治疗尚未出现2型糖尿病但存在发展为该病风险的个体的方法，该方法包括向需要该方法的个体施用有效量的糖原磷酸化酶抑制剂；有效量的糖原磷酸化酶抑制剂和非糖原磷酸化酶抑制的抗糖尿病剂；或者有效量的糖原磷酸化酶抑制剂和抗肥胖剂。本发明还提供了一种预防性地治疗尚未出现2型糖尿病但存在发展为该病风险的个体的方法，该方法包括向需要该方法的个体施用包含有效量的糖原磷酸化酶抑制剂和非糖原磷酸化酶抑制的抗糖尿病剂的药物组合物；或者有效量的糖原磷酸化酶抑制剂和抗肥胖剂。
• 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。
• Heterocyclic compounds
  申请人：——

  公开号：US20040048878A1

  公开（公告）日：2004-03-11

  Certain thienopyrrolyl and furanopyrrolyl compounds are disclosed as useful to treat or prevent disorders and conditions mediated by the histamine H 4 receptor, including allergic rhinitis.

  某些噻吡咯基和呋咯咯基化合物被披露为治疗或预防由组胺H4受体介导的疾病和症状，包括过敏性鼻炎。
• Synthesis of Oxidized Thienopyrroles using HOF·CH₃CN
  作者：Neta Shefer、Shlomo Rozen

  DOI：10.1021/jo200534p

  日期：2011.6.3

  An efficient transformation of the sulfur atoms to the sulfonyl group in a range of thienopyrroles was achieved by using the HOF·CH3CN complex. Mild conditions, high yields, and easy purification are the main features of this novel route. Most new materials exhibit considerable red-shift absorptions in the UV/visible range relative to the parent compounds.

  通过使用HOF·CH 3 CN络合物，可以在一定范围的噻吩并吡咯中将硫原子有效转化为磺酰基。温和的条件，高收率和易于纯化是该新途径的主要特征。相对于母体化合物，大多数新材料在UV /可见光范围内均显示出可观的红移吸收。
• 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。