8-bromo-1-(5-methoxypyridin-3-yl)-4-methyl[1,2,4]triazolo [4,3-a]quinoxaline | 1417410-25-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 8-bromo-1-(5-methoxypyridin-3-yl)-4-methyl[1,2,4]triazolo [4,3-a]quinoxaline
• 英文别名: 8-Bromo-1-(5-methoxypyridin-3-yl)-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline；8-bromo-1-(5-methoxypyridin-3-yl)-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline
• CAS: 1417410-25-3
• 化学式: C₁₆H₁₂BrN₅O
• 分子量: 370.208
• InChiKey: VTCJWGQRODMDTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  65.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (morpholin-4-yl)methyltrifluoroborate 、 8-bromo-1-(5-methoxypyridin-3-yl)-4-methyl[1,2,4]triazolo [4,3-a]quinoxaline 在 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl 、 palladium diacetate 、 caesium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 1-(5-methoxypyridin-3-yl)-4-methyl-8-(morpholin-4-ylmethyl)[1,2,4]triazolo[4,3-a]quinoxaline
  参考文献：
  名称：

  Structure-Based Design of a Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement

  摘要：

  Structure-guided design led to the identification of the novel, potent, and selective phosphodiesterase 2 (PDE2) inhibitor 12. Compound 12 demonstrated a >210-fold selectivity versus PDE10 and PDE11 and was inactive against all other PDE family members up to 10 mu M. In vivo evaluation of 12 provided evidence that it is able to engage the target and to increase cGMP levels in relevant brain regions. Hence, 12 is a valuable tool compound for the better understanding of the role of PDE2 in cognitive impairment and other central nervous system related disorders.

  DOI：

  10.1021/ml500262u
• 作为产物：
  描述：

  5-甲氧基吡啶-3-羧酸甲酯 在 hydrazine hydrate 作用下， 以 乙醇 、 正丁醇 为溶剂， 反应 2.0h， 生成 8-bromo-1-(5-methoxypyridin-3-yl)-4-methyl[1,2,4]triazolo [4,3-a]quinoxaline
  参考文献：
  名称：

  Structure-Based Design of a Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement

  摘要：

  Structure-guided design led to the identification of the novel, potent, and selective phosphodiesterase 2 (PDE2) inhibitor 12. Compound 12 demonstrated a >210-fold selectivity versus PDE10 and PDE11 and was inactive against all other PDE family members up to 10 mu M. In vivo evaluation of 12 provided evidence that it is able to engage the target and to increase cGMP levels in relevant brain regions. Hence, 12 is a valuable tool compound for the better understanding of the role of PDE2 in cognitive impairment and other central nervous system related disorders.

  DOI：

  10.1021/ml500262u

文献信息

• [EN] 1-ARYL-4-METHYL-[1,2,4]TRIAZOLO[4,3-a]QUINOXALINE DERIVATIVES<br/>[FR] DÉRIVÉS DE 1-ARYL-4-MÉTHYL-[1,2,4]TRIAZOLO[4,3-A]QUINOXALINE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2013000924A1

  公开（公告）日：2013-01-03

  The present invention relates to novel l-aryl-4-methyl-[l,2,4]triazolo[4,3-a]- quinoxaline derivatives as inhibitors of phosphodiesterase 2 (PDE2) and to a lesser extent of phosphodiesterase 10 (PDE10) or as inhibitors of both, phosphodiesterases 2 and 10. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which PDE2 is involved, or disorders in which both PDE2 and PDE10 are involved, such as neurological and psychiatric disorders, and endocrinological or metabolic diseases. The present invention also relates to radiolabeled compounds which may be useful for imaging and quantifying the PDE2 enzyme in tissues, using positron- emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo and to precursors of said compounds.

  本发明涉及新型的l-芳基-4-甲基-[1,2,4]三唑并[4,3-a]-喹喔啉衍生物，作为磷酸二酯酶2（PDE2）的抑制剂，以及在较小程度上作为磷酸二酯酶10（PDE10）的抑制剂或作为磷酸二酯酶2和10的双重抑制剂。该发明还涉及包含这类化合物的药物组合物，用于制备这类化合物和组合物的方法，以及将这类化合物和组合物用于预防和治疗涉及PDE2的疾病或涉及PDE2和PDE10的疾病，如神经和精神疾病，内分泌或代谢性疾病。本发明还涉及可能用于组织中PDE2酶的成像和定量的放射标记化合物，使用正电子发射断层扫描（PET）。该发明还涉及包含这类化合物的组合物，用于制备这类化合物和组合物的方法，将这类化合物和组合物用于体内或体外成像组织、细胞或宿主，并涉及这类化合物的前体。
• 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivatives
  申请人：Andrés-Gil José Ignacio

  公开号：US10604523B2

  公开（公告）日：2020-03-31

  The present invention relates to novel 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives as inhibitors of phosphodiesterase 2 (PDE2) and to a lesser extent of phosphodiesterase 10 (PDE10) or as inhibitors of both, phosphodiesterases 2 and 10. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which PDE2 is involved, or disorders in which both PDE2 and PDE10 are involved, such as neurological and psychiatric disorders, and endocrinological or metabolic diseases. The present invention also relates to radiolabelled compounds which may be useful for imaging and quantifying the PDE2 enzyme in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo and to precursors of said compounds.

  本发明涉及新型 1-芳基-4-甲基-[1,2,4]三唑并[4,3-a]-喹喔啉衍生物，该衍生物是磷酸二酯酶 2 (PDE2) 的抑制剂，其次是磷酸二酯酶 10 (PDE10) 的抑制剂，或者是磷酸二酯酶 2 和 10 两者的抑制剂。本发明还涉及包含此类化合物的药物组合物、制备此类化合物和组合物的工艺，以及将此类化合物和组合物用于预防和治疗涉及 PDE2 的疾病或涉及 PDE2 和 PDE10 的疾病，如神经和精神疾病以及内分泌或代谢疾病。本发明还涉及放射性标记化合物，该化合物可用于利用正电子发射断层扫描（PET）对组织中的 PDE2 酶进行成像和量化。本发明还涉及包含此类化合物的组合物，制备此类化合物和组合物的工艺，使用此类化合物和组合物对组织、细胞或宿主进行体外或体内成像，以及所述化合物的前体。
• 1-ARYL-4-METHYL-[1,2,4]TRIAZOLO[4,3-a]QUINOXALINE DERIVATIVES
  申请人：Janssen Pharmaceutica, N.V.

  公开号：EP2723744A1

  公开（公告）日：2014-04-30
• Structure-Based Design of a Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement
  作者：Peter Buijnsters、Meri De Angelis、Xavier Langlois、Frederik J. R. Rombouts、Wendy Sanderson、Gary Tresadern、Alison Ritchie、Andrés A. Trabanco、Greet VanHoof、Yves Van Roosbroeck、José-Ignacio Andrés

  DOI：10.1021/ml500262u

  日期：2014.9.11

  Structure-guided design led to the identification of the novel, potent, and selective phosphodiesterase 2 (PDE2) inhibitor 12. Compound 12 demonstrated a >210-fold selectivity versus PDE10 and PDE11 and was inactive against all other PDE family members up to 10 mu M. In vivo evaluation of 12 provided evidence that it is able to engage the target and to increase cGMP levels in relevant brain regions. Hence, 12 is a valuable tool compound for the better understanding of the role of PDE2 in cognitive impairment and other central nervous system related disorders.