3-aminomethyl-4-phenylisoxazole | 403860-30-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-aminomethyl-4-phenylisoxazole
• 英文别名: (4-Phenyl-1,2-oxazol-3-yl)methanamine
• CAS: 403860-30-0
• 化学式: C₁₀H₁₀N₂O
• 分子量: 174.202
• InChiKey: FPWBTKXHZVMJPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  52
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-aminomethyl-4-phenylisoxazole 、 7-(2-bromoethyl)-8-(bromomethyl)-1,3-dimethylpurine-2,4-dione 在 N,N-二异丙基乙胺 作用下， 以 乙二醇二甲醚 为溶剂， 以41%的产率得到1,3-dimethyl-8-((4-phenylisoxazol-3-yl)methyl)-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione
  参考文献：
  名称：

  8-Substituted 1,3-dimethyltetrahydropyrazino[2,1-f]purinediones: Water-soluble adenosine receptor antagonists and monoamine oxidase B inhibitors

  摘要：

  Multitarget approaches, i.e., addressing two or more targets simultaneously with a therapeutic agent, are hypothesized to offer additive therapeutic benefit for the treatment of neurodegenerative diseases. Validated targets for the treatment of Parkinson's disease are, among others, the A(2A) adenosine receptor (AR) and the enzyme monoamine oxidase B (MAO-B). Additional blockade of brain A(1) ARs may also be beneficial. We recently described 8-benzyl-substituted tetrahydropyrazino[2,1-f]purinediones as a new lead structure for the development of such multi-target drugs. We have now designed a new series of tetrahydropyrazino[2,1-f]purinediones to extensively explore their structure-activity-relationships. Several compounds blocked human and rat A(1) and A(2A)ARs at similar concentrations representing dual A(1)/A(2A) antagonists with high selectivity versus the other AR subtypes. Among the best dual A(1)/A(2A)AR antagonists were 8-(3-(4-chlorophenyl)propy1)-1,3-dimethyl-6,7,8,9-tetrahydropyrazino[2,1-flpurine-2,4(1H,3H)-dione (41,K-i human A(1): 65.5 nM, A(2A): 230 nM; K-1 rat A(1): 352 nM, A(2A): 316 nM) and 1,3-dimethy1-84(2(thiophen-2-yl)thiazol-4-y1)methyl)-6,7,8,9-tetrahydropyrazino[2,1-fjpurine-2,4(1H,3H)-dione (57, K-i human A(1): 642 nM, A(2A): 203 nM; K-i rat A(1): 166 nM, A(2A): 121 nM). Compound 57 was found to be well water-soluble (0.7 mg/mL) at a physiological pH value of 7.4. One of the new compounds showed triple -target inhibition: (R)-1,3-dimethy1-8-(2,1,3,4-tetrahydronaphthalen-1-y1)-6,7,8,9-tetrahydropyrazino[2,1-Apurine-2,4(1H,3H)-dione (49) was about equipotent at A(1) and A(2A)ARs and at MAO-B (K-i human A(1): 393 nM, human A(2A): 595 nM, IC50 human MAO-B: 210 nM) thus allowing future in vivo explorations of the intended multi-target approach. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.09.003
• 作为产物：
  描述：

  4-phenyl-3-phthalimidomethylisoxazole 在 肼 、 盐酸 、 碳酸氢钠 作用下， 以 甲醇 、 水 为溶剂， 反应 0.5h， 生成 3-aminomethyl-4-phenylisoxazole
  参考文献：
  名称：

  Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors

  摘要：

  杂环酰胺衍生物的化学式（I）：其中—X-Y-Z-选择自—S—CR4═CR5—，—CR4═CR5—S—，—O—CR4═CR5—，—CR4═CR5—O—，—N═CR4—S—，—S—CR4═N—，—NR6—CR4═CR5—和—CR4═CR5—NR6—；或其药学上可接受的盐或体内可水解酯；（附带条件）；具有糖原磷酸化酶抑制活性，因此在治疗与糖原磷酸化酶活性增加相关的疾病状态中具有价值。描述了制备所述杂环酰胺衍生物和含有它们的药物组合物的方法。

  公开号：

  US20030232875A1

文献信息

• BICYCLIC PYRROLYL AMIDES AS GLUCOGEN PHOSPHORYLASE INHIBITORS
  申请人：AstraZeneca AB

  公开号：EP1317459A1

  公开（公告）日：2003-06-11
• [EN] BICYCLIC PYRROLYL AMIDES AS GLUCOGEN PHOSPHORYLASE INHIBITORS<br/>[FR] AMIDES DE PYRROLYLE BICYCLIQUES SERVANT D'INHIBITEURS DE GLYCOGENE PHOSPHORYLASE
  申请人：ASTRAZENECA AB

  公开号：WO2002020530A1

  公开（公告）日：2002-03-14

  Heterocyclic amide derivatives, of formula (I): wherein -X-Y-Z- is selected from -S-CR?4=CR5-, -CR4=CR5¿-S-, -O-CR?4=CR5-, -CR4=CR5¿-O-, -N=CR4-S-, -S-CR4=N-, -NR?6-CR4=CR5¿- and -CR?4=CR5-NR6¿-; or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof; (with provisos); possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.
• Bicyclic pyrrolyl amides as glucogen phosphorylase inhibitors
  申请人：——

  公开号：US20030232875A1

  公开（公告）日：2003-12-18

  Heterocyclic amide derivatives, of formula (I): wherein —X-Y-Z- is selected from —S—CR 4 ═CR 5 —, —CR 4 ═CR 5 —S—, —O—CR 4 ═CR 5 —, —CR 4 ═CR 5 —O—, —N═CR 4 —S—, —S—CR 4 ═N—, —NR 6 —CR 4 ═CR 5 — and —CR 4 ═CR 5 —NR 6 —; or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof; (with provisos); possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.

  杂环酰胺衍生物的化学式（I）：其中—X-Y-Z-选择自—S—CR4═CR5—，—CR4═CR5—S—，—O—CR4═CR5—，—CR4═CR5—O—，—N═CR4—S—，—S—CR4═N—，—NR6—CR4═CR5—和—CR4═CR5—NR6—；或其药学上可接受的盐或体内可水解酯；（附带条件）；具有糖原磷酸化酶抑制活性，因此在治疗与糖原磷酸化酶活性增加相关的疾病状态中具有价值。描述了制备所述杂环酰胺衍生物和含有它们的药物组合物的方法。
• 8-Substituted 1,3-dimethyltetrahydropyrazino[2,1-f]purinediones: Water-soluble adenosine receptor antagonists and monoamine oxidase B inhibitors
  作者：Andreas Brunschweiger、Pierre Koch、Miriam Schlenk、Muhammad Rafehi、Hamid Radjainia、Petra Küppers、Sonja Hinz、Felipe Pineda、Michael Wiese、Jörg Hockemeyer、Jag Heer、Frédéric Denonne、Christa E. Müller

  DOI：10.1016/j.bmc.2016.09.003

  日期：2016.11

  Multitarget approaches, i.e., addressing two or more targets simultaneously with a therapeutic agent, are hypothesized to offer additive therapeutic benefit for the treatment of neurodegenerative diseases. Validated targets for the treatment of Parkinson's disease are, among others, the A(2A) adenosine receptor (AR) and the enzyme monoamine oxidase B (MAO-B). Additional blockade of brain A(1) ARs may also be beneficial. We recently described 8-benzyl-substituted tetrahydropyrazino[2,1-f]purinediones as a new lead structure for the development of such multi-target drugs. We have now designed a new series of tetrahydropyrazino[2,1-f]purinediones to extensively explore their structure-activity-relationships. Several compounds blocked human and rat A(1) and A(2A)ARs at similar concentrations representing dual A(1)/A(2A) antagonists with high selectivity versus the other AR subtypes. Among the best dual A(1)/A(2A)AR antagonists were 8-(3-(4-chlorophenyl)propy1)-1,3-dimethyl-6,7,8,9-tetrahydropyrazino[2,1-flpurine-2,4(1H,3H)-dione (41,K-i human A(1): 65.5 nM, A(2A): 230 nM; K-1 rat A(1): 352 nM, A(2A): 316 nM) and 1,3-dimethy1-84(2(thiophen-2-yl)thiazol-4-y1)methyl)-6,7,8,9-tetrahydropyrazino[2,1-fjpurine-2,4(1H,3H)-dione (57, K-i human A(1): 642 nM, A(2A): 203 nM; K-i rat A(1): 166 nM, A(2A): 121 nM). Compound 57 was found to be well water-soluble (0.7 mg/mL) at a physiological pH value of 7.4. One of the new compounds showed triple -target inhibition: (R)-1,3-dimethy1-8-(2,1,3,4-tetrahydronaphthalen-1-y1)-6,7,8,9-tetrahydropyrazino[2,1-Apurine-2,4(1H,3H)-dione (49) was about equipotent at A(1) and A(2A)ARs and at MAO-B (K-i human A(1): 393 nM, human A(2A): 595 nM, IC50 human MAO-B: 210 nM) thus allowing future in vivo explorations of the intended multi-target approach. (C) 2016 Elsevier Ltd. All rights reserved.