7-bromo-3-methylquinoxalin-2(1H)-one | 103095-19-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 7-bromo-3-methylquinoxalin-2(1H)-one
• 英文别名: 7-bromo-3-methyl-1H-quinoxalin-2-one
• CAS: 103095-19-8
• 化学式: C₉H₇BrN₂O
• 分子量: 239.071
• InChiKey: NBISGWQFJNEDOE-UHFFFAOYSA-N

物化性质

• 熔点：
  291-293 °C (decomp)(Solv: ethanol (64-17-5))
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-bromo-3-methylquinoxalin-2(1H)-one 在 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl 、 palladium diacetate 、 caesium carbonate 、 三氯氧磷 作用下， 以 四氢呋喃 、 水 、 1,2-二氯乙烷 、 正丁醇 为溶剂， 反应 18.0h， 生成 1-(2-chloro-5-propoxyphenyl)-4-methyl-8-(morpholin-4-ylmethyl)[1,2,4]triazolo[4,3-a]quinoxaline hydrochloride
  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：

  2-(4-bromo-2-nitrophenylamino)propionic acid 在 双氧水 、 铁粉 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 8.0h， 生成 7-bromo-3-methylquinoxalin-2(1H)-one
  参考文献：
  名称：

  [EN] TRIAZOLOPYRAZINE DERIVATIVES AND THEIR USE FOR TREATING NEUROLOGICAL AND PSYCHIATRIC DISORDERS
  [FR] DÉRIVÉS DE TRIAZOLOPYRAZINE ET LEUR UTILISATION POUR LE TRAITEMENT DE TROUBLES NEUROLOGIQUES ET PSYCHIATRIQUES

  摘要：

  本发明涉及式(I)的三唑吡嗪化合物。该发明的不同方面涉及包含所述化合物的药物组合物以及将该化合物用作治疗神经系统和精神疾病的治疗剂的用途。

  公开号：

  WO2013034755A1

文献信息

• Discovery of a new series of [1,2,4]triazolo[4,3-a]quinoxalines as dual phosphodiesterase 2/phosphodiesterase 10 (PDE2/PDE10) inhibitors
  作者：José-Ignacio Andrés、Peter Buijnsters、Meri De Angelis、Xavier Langlois、Frederik Rombouts、Andrés A. Trabanco、Greet Vanhoof

  DOI：10.1016/j.bmcl.2012.11.077

  日期：2013.2

  The synthesis, preliminary evaluation and structure–activity relationship (SAR) of a series of 1-aryl-4-methyl[1,2,4]triazolo[4,3-a]quinoxalines as dual phosphodiesterase 2/phosphodiesterase 10 (PDE2/PDE10) inhibitors are described. From this investigation compound 31 was identified, showing good combined potency, acceptable brain uptake and high selectivity for both PDE2 and PDE10 enzymes. Compound

  一系列1-芳基-4-甲基[1,2,4]三唑并[4,3- a ]喹喔啉作为双磷酸二酯酶2 /磷酸二酯酶10（PDE2 /描述了PDE10）抑制剂。从该研究中鉴定出化合物31，对PDE2和PDE10酶均显示出良好的综合效价，可接受的大脑摄取和高选择性。化合物31在大鼠中进行了微剂量实验，显示了在PDE2和PDE10均高表达的大脑区域中的优先分布。这些有希望的结果可能会推动高效联合PDE2 / PDE10抑制剂，甚至PDE2和/或PDE10选择性抑制剂的进一步开发。
• [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。
• [EN] COMBINATIONS COMPRISING PDE 2 INHIBITORS SUCH AS 1-ARYL-4-METHYL- [1,2,4] TRIAZOLO [4,3-A] QUINOXALINE COMPOUNDS AND PDE 10 INHIBITORS FOR USE IN THE TREATMENT OF NEUROLOGICAL OR METABOLIC DISORDERS<br/>[FR] COMBINAISONS COMPRENANT DES INHIBITEURS DE LA PDE 2 TELS QUE DES COMPOSÉS 1-ARYL-4-MÉTHYL-[1, 2, 4] TRIAZOLO [4, 3-A]-QUINOXALINE ET DES INHIBITEURS DE LA PDE 10 POUR UTILISATION DANS LE TRAITEMENT DE TROUBLES NEUROLOGIQUES OU MÉTABOLIQUES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2014001314A1

  公开（公告）日：2014-01-03

  The present invention relates to combinations of phosphodiesterase 2 (PDE2) inhibitors with inhibitors of phosphodiesterase 10 (PDE 10). In particular, the invention relates to combinations of 1-aryl-4- methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives which have been found to inhibit phosphodiesterase 2 (PDE2), with inhibitors of phosphodiesterase 10 (PDE10). Particular PDE10 inhibitors are selected from the group of MP-10, PQ-10, TP-10, papaverine, and the compounds disclosed in WO 2011/051342 and in WO 2011/110545. The invention is also directed to pharmaceutical compositions comprising such combinations, to processes for preparing such compositions, to the use of PDE2 inhibitors, in particular of 1- aryl-4-methyl- [1,2,4]triazolo[4,3-a]-quinoxaline derivatives for the potentiation of said PDE10 inhibitors, and to the use of said PDE10 inhibitors for the potentiation of the effect of said PDE2 inhibitors, in particular, 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives, and to the use of such combinations and compositions for the prevention and treatment of disorders in which PDE2 and PDE10 are involved, such as neurological and psychiatric disorders, and endocrinological or metabolic diseases.

  本发明涉及磷酸二酯酶2（PDE2）抑制剂与磷酸二酯酶10（PDE 10）抑制剂的组合物。具体地，本发明涉及已被发现能够抑制磷酸二酯酶2（PDE2）的1-芳基-4-甲基-[1,2,4]三唑并[4,3-a]-喹喔啉衍生物与磷酸二酯酶10（PDE10）抑制剂的组合物。特定的PDE10抑制剂选自MP-10、PQ-10、TP-10、罂粟碱以及WO 2011/051342和WO 2011/110545中披露的化合物。本发明还涉及包含这种组合物的药物组合物、制备这种组合物的工艺、使用PDE2抑制剂，特别是1-芳基-4-甲基-[1,2,4]三唑并[4,3-a]-喹喔啉衍生物来增强所述PDE10抑制剂的作用，以及使用所述PDE10抑制剂来增强所述PDE2抑制剂的作用，特别是1-芳基-4-甲基-[1,2,4]三唑并[4,3-a]-喹喔啉衍生物，以及使用这种组合物和组合物预防和治疗涉及PDE2和PDE10的疾病，如神经和精神疾病以及内分泌或代谢性疾病。
• Synthesis of isomeric (E)-[4-(dimethylamino)phenyl]-vinylquinoxalines – precursors for a new class of nonlinear optical chromophores
  作者：Sirina M. Sharipova、Alina A. Gilmutdinova、Dmitry B. Krivolapov、Zilya R. Khisametdinova、Olga N. Kataeva、Alexey A. Kalinin

  DOI：10.1007/s10593-017-2084-y

  日期：2017.5

  hyde at 220°С in the presence of catalytic amounts of acetic anhydride and pyridine during the synthesis of 3-(dimethylaminophenylethenyl)quinoxalin-2-ones or as a result of condensation of these reactants by the action of 20 М sodium hydroxide solution in the presence of Aliquat 336 during the synthesis of 3-(dimethylaminophenylethenyl)-2-phenylquinoxalines. The introduction of dimethylanilinoethenyl

  提出了制备异构体（Е）-3-，（Е）-6-，（Е的方法）-7- [4-（二甲基氨基）苯基乙烯基]喹喔啉-2-酮和2-苯基喹喔啉–“给体-π-桥”型化合物，用作新型非线性光学发色团的前体，其潜在的第一超极化率很高。在合成催化过程中，在催化量的乙酸酐和吡啶存在下，在220℃催化3-甲基衍生物与4-（二甲基氨基）苯甲醛的熔融反应，可以实现高收率地在喹喔啉系统的3位引入二甲基苯胺基乙烯基部分。 3-（二甲基氨基苯基乙烯基）喹喔啉-2-酮或在3-（二甲基氨基苯基乙烯基）-2-苯基喹喔啉合成期间在Aliquat 336存在下通过20 M氢氧化钠溶液作用使这些反应物缩合的结果。在乙酸钯存在下，将对二甲基氨基乙烯基苯与6-或7-溴喹喔啉合并使用。通过X射线衍射分析证实了喹喔啉的异构体6-溴-和7-溴-3-甲基衍生物的结构。
• The hamburger-shape photocatalyst: thioxanthone-based chiral [2.2]paracyclophane for enantioselective visible-light photocatalysis of 3-methylquinoxalin-2(1<i>H</i>)-one and styrenes
  作者：Shou-Chih Huo、Ranadheer Reddy Indurmuddam、Bor-Cherng Hong、Chuan-Fu Lu、Su-Ying Chien

  DOI：10.1039/d3ob01580g

  日期：——

  A new thioxanthone-based photocatalyst with a [2.2]paracyclophane skeleton and planar chirality has been developed and utilized in the visible light-mediated enantioselective aza Patern–Büchi reaction.

  我们开发了一种新的基于硫氧杂环酮的光催化剂，它具有 [2.2]paracyclophane 骨架和平面手性，可用于可见光介导的对映体选择性 aza Patern-Büchi 反应。