4-chloro-7-methylpyrrolo[1,2-a]quinoxaline | 160657-06-7

• 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: 4-chloro-7-methylpyrrolo[1,2-a]quinoxaline
• CAS: 160657-06-7
• 化学式: C₁₂H₉ClN₂
• 分子量: 216.67
• InChiKey: HXYUSHANYDBRHI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  17.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(4-氟苄基)哌嗪 、 4-chloro-7-methylpyrrolo[1,2-a]quinoxaline 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 4-[4-(4-fluorobenzyl)piperazino]-7-methylpyrrolo[1,2-a]quinoxaline
  参考文献：
  名称：

  Novel and Selective Partial Agonists of 5-HT₃ Receptors. 2. Synthesis and Biological Evaluation of Piperazinopyridopyrrolopyrazines, Piperazinopyrroloquinoxalines, and Piperazinopyridopyrroloquinoxalines

  摘要：

  In continuation of our previous work on piperazinopyrrolothienopyrazine derivatives, three series of piperazinopyridopyrrolopyrazines, piperazinopyrroloquinoxalines, and piperazinopyridopyrrolaquinoxalines were prepared and evaluated as 5-HT3 receptor ligands. The chemical modifications performed within these new series led to structure-activity relationships regarding both high affinity and selectivity for the 5-HT3 receptors that are in agreement with those established previously for the pyrrolothienopyrazine series. The best compound (8a) obtained in these new series is in the picomolar range of affinity for 5-HT3 receptors with a selectivity higher than 10(6). Four of the high-affinity 5-HT3 ligands (8a, 15a,b, and 16d) were selected in both the pyridopyrrolopyrazine and the pyrroloquinoxaline series and were characterized in vitro and in vivo as agonists or partial agonists. Compound 8a was also evaluated in the light/dark test where it showed potential anxiolytic-like activity at very low doses per os.

  DOI：

  10.1021/jm960501o
• 作为产物：
  描述：

  5-甲基-2-(1H-吡咯-1-基)苯胺 在 吡啶 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 7.0h， 生成 4-chloro-7-methylpyrrolo[1,2-a]quinoxaline
  参考文献：
  名称：

  Novel and Selective Partial Agonists of 5-HT₃ Receptors. 2. Synthesis and Biological Evaluation of Piperazinopyridopyrrolopyrazines, Piperazinopyrroloquinoxalines, and Piperazinopyridopyrroloquinoxalines

  摘要：

  In continuation of our previous work on piperazinopyrrolothienopyrazine derivatives, three series of piperazinopyridopyrrolopyrazines, piperazinopyrroloquinoxalines, and piperazinopyridopyrrolaquinoxalines were prepared and evaluated as 5-HT3 receptor ligands. The chemical modifications performed within these new series led to structure-activity relationships regarding both high affinity and selectivity for the 5-HT3 receptors that are in agreement with those established previously for the pyrrolothienopyrazine series. The best compound (8a) obtained in these new series is in the picomolar range of affinity for 5-HT3 receptors with a selectivity higher than 10(6). Four of the high-affinity 5-HT3 ligands (8a, 15a,b, and 16d) were selected in both the pyridopyrrolopyrazine and the pyrroloquinoxaline series and were characterized in vitro and in vivo as agonists or partial agonists. Compound 8a was also evaluated in the light/dark test where it showed potential anxiolytic-like activity at very low doses per os.

  DOI：

  10.1021/jm960501o

文献信息

• Pyrroloquinoxaline Derivatives as High-Affinity and Selective 5-HT₃ Receptor Agonists:  Synthesis, Further Structure−Activity Relationships, and Biological Studies
  作者：Giuseppe Campiani、Elena Morelli、Sandra Gemma、Vito Nacci、Stefania Butini、Michel Hamon、Ettore Novellino、Giovanni Greco、Alfredo Cagnotto、Mara Goegan、Luigi Cervo、Fabio Dalla Valle、Claudia Fracasso、Silvio Caccia、Tiziana Mennini

  DOI：10.1021/jm990151g

  日期：1999.10.1

  [(3)H]zacopride binding. The SAR studies detailed herein delineated a number of structural features required for improving affinity. Some of the ligands were employed as "molecular yardsticks" to probe the spatial dimensions of the lipophilic pockets L1, L2, and L3 in the 5-HT(3) receptor cleft, while the 7-OH pyrroloquinoxaline analogue was designed to investigate hydrogen bonding with a putative receptor site

  描述了一系列新型吡咯并喹喔啉和杂芳族相关衍生物的合成，药理评价和构效关系（SAR）。新的吡咯并喹喔啉相关配体在大鼠皮层，表达高密度5-HT（3）受体的组织中以及在NG108-15细胞上进行了测试，并在低纳摩尔或亚纳摩尔范围内表现出IC（50）值，方法是通过抑制[（3）H] zacopride结合。本文详述的SAR研究描述了改善亲和力所需的许多结构特征。一些配体被用作“分子尺度”，以探测5-HT（3）受体裂隙中亲脂性口袋L1，L2和L3的空间尺寸，而7-OH吡咯并喹喔啉类似物被设计用于研究与可能与5-羟色胺羟基相互作用的假定受体位点H1的氢键作用。最活跃的吡咯并喹喔啉衍生物对5-HT（3）受体显示亚纳摩尔亲和力。在功能研究中（[[14] C]胍在NG108-15杂化细胞中的体外积累试验），大多数受试化合物均显示出明确的5-HT（3）激动剂特性，而另一些则为部分激动剂。关于5-HT（3）亲和力
• Access to quinolinones <i>via</i> DMAP-catalysed cascade reaction of 2-substituted benzoic acids with organic azides
  作者：Yuan-Yuan He、Mei-Shan Zhu、Yang Gao、Xiao-Qiang Hu

  DOI：10.1039/d2cc04406d

  日期：——

  DMAP-catalysed Curtius rearrangement and intramolecular cyclisation cascade reaction of 2-substituted aryl carboxylic acids with organic azides for the first time. This protocol features simple operation, broad scope and metal-free conditions, furnishing a broad spectrum of biologically attractive heterocycles. The synthetic virtue of this reaction was demonstrated by gram-scale synthesis and applicability toward

  在此，我们首次报道了 DMAP 催化的 Curtius 重排和 2-取代芳基羧酸与有机叠氮化物的分子内环化级联反应。该协议具有操作简单、范围广和无金属条件的特点，提供了广泛的具有生物吸引力的杂环。该反应的合成优点通过克级合成和对药物样分子的适用性得到证明。
• Dérivés de pyrrolopyrazines à activité 5-HT3
  申请人：ADIR ET COMPAGNIE

  公开号：EP0623620A1

  公开（公告）日：1994-11-09

  La présente invention concerne les composés de formule (I) : dans laquelle A et R₁ sont tels que définis dans la description. Médicaments.

  本发明涉及式（I）化合物： 其中 A 和 R₁ 如描述中所定义。 药物。
• US5599812A
  申请人：——

  公开号：US5599812A

  公开（公告）日：1997-02-04
• [EN] ETHER DERIVATIVES OF PYRROLO[1,2-A]QUINOXALINES, METHOD FOR PRODUCING THEM AND THEIR USE IN THERAPY<br/>[FR] DERIVES ETHERS DE PYRROLO[1,2-A]QUINOXALINES, LEUR PROCEDE DE PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE
  申请人：UNIV CAEN BASSE NORMANDIE

  公开号：WO2001014381A1

  公开（公告）日：2001-03-01

  L'invention concerne des dérivés répondant à la formule (I), dans laquelle: n est égal à zéro ou est un nombre entier de 1 à 4; R1 représente un atome d'hydrogène ou un groupe alkyle, phényle ou phényle substitué par halogène, alkyle ou alkoxy; R2 représente un groupe aminé ou bien quand n = 0, R2 forme conjointement avec -(a)- un groupe bicyclique ou azabicyclique, à 7 ou 8 chaînons; et Ar est l'un des groupes des formules (A, B, C, D, E) ainsi que les sels de ces dérivés. Elle concerne également l'application pharmaceutique de ces dérivés et sels, notamment en tant qu'antagonistes vis-à-vis de la réponse induite par la sérotonine, antidépresseurs ou agents pour le traitement des troubles mnésiques.