1-甲基-3-溴甲基喹喔啉-2-酮 | 1501-41-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 1-甲基-3-溴甲基喹喔啉-2-酮
• 英文名称: 3-bromomethyl-1H-1-methylquinoxalin-2-one
• 英文别名: 2-Brommethyl-3.4-dihydro-4-methyl-3-oxo-chinoxalin；2-Brommethyl-4-methyl-3(4H)-chinoxalon；3-bromomethyl-1-methyl-1H-quinoxalin-2-one；1-Methyl-3-bromomethyl-2(1H)-quinoxalinone；3-(Bromomethyl)-1-methylquinoxalin-2(1h)-one；3-(bromomethyl)-1-methylquinoxalin-2-one
• CAS: 1501-41-3
• 化学式: C₁₀H₉BrN₂O
• mdl: MFCD13192552
• 分子量: 253.098
• InChiKey: UADIEAODWPWLFL-UHFFFAOYSA-N

物化性质

• 熔点：
  193 °C (decomp)
• 沸点：
  350.4±44.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  对羟基联苯 、 1-甲基-3-溴甲基喹喔啉-2-酮 在 sodium hydroxide 、 苄基三乙基氯化铵 作用下， 以 氯仿 为溶剂， 以27%的产率得到1-Methyl-3-[(4-phenylphenoxy)methyl]quinoxalin-2-one
  参考文献：
  名称：

  Structure−Activity Studies of Substituted Quinoxalinones as Multiple-Drug-Resistance Antagonists

  摘要：

  A significant problem in the clinical treatment of cancer relates to the development of tumor resistance to many chemotherapeutic agents. Acquired drug resistance is often mediated through overexpression of membrane transport proteins that effectively efflux anticancer agents. Two of the best-studied transporters, P-glycoprotein (Pgp) and MRP1, have pharmacological properties that only partially overlap. In our search for improved drug-resistance antagonists, we have identified a family of substituted quinoxalines that selectively antagonizes Pgp over MRP1. Consequently, a focused library of congeners was designed and synthesized starting with a parent bromomethylquinoxalinone. This parent quinoxalinone was then condensed with a series of phenols to yield a family of substituted phenoxymethylquinoxalinones. These compounds were evaluated for their toxicity toward drug-sensitive MCF-7 breast carcinoma cells and for their abilities to antagonize Pgp and MRP1 in drug-resistant cell lines (NCI/ADR and MCF-7/VP, respectively). The results of this structure-activity study indicate that compounds with carbonyl substitutions of the phenoxy group tester, amide, or ketone moieties) demonstrate excellent antagonism of Pgp while having relatively low toxicity toward drug-sensitive cells. Importantly, none of these compounds antagonized MRP1. Because of their transporter selectivity, we predict that substituted quinoxalinones may be more effective MDR modulators in vivo than are nonselective transporter antagonists.

  DOI：

  10.1021/jm000282d
• 作为产物：
  描述：

  1,3-二甲基-2-喹噁啉酮 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 12.0h， 以52%的产率得到1-甲基-3-溴甲基喹喔啉-2-酮
  参考文献：
  名称：

  氨基酰氨基杂环与CH甲基化的CH甲基化。

  摘要：

  N杂环的直接甲基化是药物，农用化学品，功能材料和其他化学实体发展的重要转变。在此，史无前例的C（sp 2描述了亚氨基酰胺杂环作为核苷碱基类似物的H-甲基化。值得注意的是，在水性条件下使用三甲基ulf盐作为甲基化剂。获得了较宽的底物范围和出色的官能团耐受性。此外，该方法可以很容易地应用于氮杂尿嘧啶核苷的位点选择性甲基化。克级反应和产物各种转化的可行性突出了所开发方法的合成潜力。联合氘标记实验有助于阐明合理的反应机理。

  DOI：

  10.1002/anie.202010958

文献信息

• [EN] BRIDGED BICYCLIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS BICYCLIQUES PONTÉS POUR LE TRAITEMENT DES INFECTIONS BACTÉRIENNES
  申请人：KYORIN SEIYAKU KK

  公开号：WO2013003383A1

  公开（公告）日：2013-01-03

  Novel bridged bicyclic compounds are disclosed herein, along with their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antibacterial agents. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating bacterial infections and associated diseases and conditions.

  本文披露了新型桥环双环化合物，以及它们的药用盐、水合物和前药。还披露了包含这些化合物的组合物，制备这些化合物的方法以及将这些化合物用作抗菌剂的方法。所披露的化合物、其药用盐、水合物和前药，以及包含这些化合物、盐、水合物和前药的组合物，可用于治疗细菌感染及相关疾病和症状。
• [EN] QUINOXALINONE-3- ONE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE QUINOXALINONE-3- ONE UTILISES COMME ANTAGONISTES DU RECEPTEUR D'OREXINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2004096780A1

  公开（公告）日：2004-11-11

  The invention relates to quinoxalinone derivatives of general Formula (I) and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as orexin receptor antagonists.General Formula (I) wherein X and R1-R9 are as defined in the description

  本发明涉及一般式(I)的喹喔啉酮衍生物及其在制备药物组合物中作为活性成分的用途。本发明还涉及相关方面，包括制备该化合物的过程，含有一个或多个该化合物的药物组合物，特别是它们作为促进睡眠的药物受体拮抗剂的用途。其中X和R1-R9如描述中所定义。
• Novel compounds for enhancing chemotherapy
  申请人：——

  公开号：US20020013322A1

  公开（公告）日：2002-01-31

  The present invention provides chemical compounds, pharmaceutical compositions, and methods for increasing the therapeutic efficacy of drugs. Specifically, the invention provides compounds and compositions for inhibiting drug transport proteins that efflux therapeutic agents from cells, and to methods for using these compounds and pharmaceutical compositions to increase the efficacy of the therapeutic agents that are effluxed by these drug transport proteins.

  本发明提供了化学化合物、药物组合物和方法，用于增强药物的治疗效果。具体地，本发明提供了抑制药物转运蛋白的化合物和组合物，这些蛋白从细胞中排出治疗剂量的药物，并提供使用这些化合物和药物组合物的方法，以增加被这些药物转运蛋白排出的治疗剂量的药物的疗效。
• Quinoxalinone compounds useful for expanding the lumina or air passages
  申请人：The Upjohn Company

  公开号：US04181724A1

  公开（公告）日：1980-01-01

  Compounds of the formula below are useful for expanding the lumina or air passages in a mammal in need of said treatment. The compounds are also useful for treating atopic eczema and urticaria. ##STR1## wherein X and Y are the same or different and are hydrogen, fluoro, chloro, bromo, nitro, trifluoromethyl, alkyl of one to four carbon atoms, inclusive, alkoxy of one to four carbon atoms, inclusive, and cyano; R.sub.1 is hydrogen, methyl or ethyl; R.sub.2 is hydrogen, alkyl of one to six carbon atoms, inclusive, phenyl, benzyl, CH.sub.2 Z wherein Z is fluoro, chloro, or bromo, CO.sub.2 M, CH.sub.2 CO.sub.2 M, CH.sub.2 CH.sub.2 CO.sub.2 M and CHR.sub.3 CO.sub.2 M wherein M is hydrogen, alkyl of one to four carbon atoms, inclusive, or a physiologically acceptable metal or amine cation and R.sub.3 is alkyl of one to three carbon atoms, inclusive, with the proviso that M is not hydrogen when R.sub.2 is CH.sub.2 CO.sub.2 M or a CHR.sub.3 CO.sub.2 M.

  以下的化合物公式对于需要扩张哺乳动物的腔道或空气通道的治疗非常有用。这些化合物也用于治疗特应性湿疹和荨麻疹。其中X和Y相同或不同，可以是氢、氟、氯、溴、硝基、三氟甲基、含1至4个碳原子的烷基、含1至4个碳原子的烷氧基和氰基；R1是氢、甲基或乙基；R2是氢、含1至6个碳原子的烷基、苯基、苄基、CH2Z（其中Z是氟、氯或溴）、CO2M、CH2CO2M、CH2CH2CO2M和CHR3CO2M，其中M是氢、含1至4个碳原子的烷基或生理上可接受的金属或胺阳离子，R3是含1至3个碳原子的烷基，但当R2为CH2CO2M或CHR3CO2M时，M不能是氢。
• Quinoxalinones useful for treating atopic eczema and urticaria
  申请人：The Upjohn Company

  公开号：US04242342A1

  公开（公告）日：1980-12-30

  Compounds of the formula below are useful for expanding the lumina of air passages in a mammal in need of said treatment. The compounds are also useful for treating atopic eczema and urticaria. ##STR1## wherein X and Y are the same or different and are hydrogen, fluoro, chloro, bromo, nitro, trifluoromethyl, alkyl of one to four carbon atoms, inclusive, alkoxy of one to four carbon atoms, inclusive, and cyano; R.sub.1 is hydrogen, methyl or ethyl; R.sub.2 is hydrogen, alkyl of one to six carbon atoms, inclusive, phenyl, benzyl, CH.sub.2 Z wherein Z is fluoro, chloro, or bromo, CO.sub.2 M, CH.sub.2 CO.sub.2 M, CH.sub.2 CH.sub.2 CO.sub.2 M and CHR.sub.3 CO.sub.2 M wherein M is hydrogen, alkyl of one to four carbon atoms, inclusive, or a physiologically acceptable metal or amine cation and R.sub.3 is alkyl of one to three carbon atoms, inclusive, with the proviso that M is not hydrogen when R.sub.2 is CH.sub.2 CO.sub.2 M or CHR.sub.3 CO.sub.2 M.

  以下式子的化合物对于需要扩张哺乳动物空气通道的治疗非常有用。该化合物也对治疗特应性湿疹和荨麻疹有用。其中X和Y相同或不同，可以是氢、氟、氯、溴、硝基、三氟甲基、含有一到四个碳原子的烷基、含有一到四个碳原子的烷氧基和氰基；R.sub.1是氢、甲基或乙基；R.sub.2是氢、含有一到六个碳原子的烷基、苯基、苄基、CH.sub.2 Z，其中Z是氟、氯或溴、CO.sub.2 M、CH.sub.2 CO.sub.2 M、CH.sub.2 CH.sub.2 CO.sub.2 M和CHR.sub.3 CO.sub.2 M，其中M是氢、含有一到四个碳原子的烷基或生理上可接受的金属或胺阳离子，R.sub.3是含有一到三个碳原子的烷基，但当R.sub.2为CH.sub.2 CO.sub.2 M或CHR.sub.3 CO.sub.2 M时，M不是氢。