4-chlorofuro[3,4-c]quinolin-1(3H)-one | 152534-86-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-chlorofuro[3,4-c]quinolin-1(3H)-one
• 英文别名: 4-Chloro-furo[3,4-c]quinolin-1(3H)-one；4-chloro-3H-furo[3,4-c]quinolin-1-one
• CAS: 152534-86-6
• 化学式: C₁₁H₆ClNO₂
• 分子量: 219.627
• InChiKey: KLSBPONMUTUMBM-UHFFFAOYSA-N

物化性质

• 熔点：
  154-156 °C
• 沸点：
  477.0±45.0 °C(predicted)
• 密度：
  1.510±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-chlorofuro[3,4-c]quinolin-1(3H)-one 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 [4-Hydroxymethyl-2-(4-methyl-piperazin-1-yl)-quinolin-3-yl]-methanol
  参考文献：
  名称：

  Further Studies on the Interaction of the 5-Hydroxytryptamine₃ (5-HT₃) Receptor with Arylpiperazine Ligands. Development of a New 5-HT₃ Receptor Ligand Showing Potent Acetylcholinesterase Inhibitory Properties

  摘要：

  Novel arylpiperazine derivatives bearing lipophilic probes were designed, synthesized, and evaluated for their potential ability to interact with the 5-hydroxytryptamine(3) (5-HT3) receptor. Most of the new compounds show subnanomolar 5-HT3 receptor affinity. Ester 6bc showing a picomolar K-i value is one of the most potent 5-HT3 receptor ligands so far synthesized. The structure-affinity relationship study suggests the existence of a certain degree of conformational freedom of the amino acid residues interacting with the substituents in positions 3 and 4 of the quipazine quinoline nucleus. Thus, the tacrine-related heterobivalent ligand 6o was designed in an attempt to capitalize on the evidence of such a steric tolerance. Compound 6o shows a nanomolar potency for both the 5-HT3 receptor and the human AChE and represents the first example of a rationally designed high-affinity 5-HT3 receptor ligand showing nanomolar AChE inhibitory activity. Finally, the computational analysis performed on compound 6o allowed the rationalization of the structure-energy determinants for AChE versus BuChE selectivity and revealed the existence of a subsite at the boundary of the 5-HT3 receptor extracellular domain, which could represent a "peripheral" site similar to that evidenced in the AChE gorge.

  DOI：

  10.1021/jm0493461
• 作为产物：
  描述：

  2-羟基-3-甲基-4-喹啉羧酸 在 N-溴代丁二酰亚胺(NBS) 、 三乙胺 、 三氯氧磷 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 34.5h， 生成 4-chlorofuro[3,4-c]quinolin-1(3H)-one
  参考文献：
  名称：

  Further Studies on the Interaction of the 5-Hydroxytryptamine₃ (5-HT₃) Receptor with Arylpiperazine Ligands. Development of a New 5-HT₃ Receptor Ligand Showing Potent Acetylcholinesterase Inhibitory Properties

  摘要：

  Novel arylpiperazine derivatives bearing lipophilic probes were designed, synthesized, and evaluated for their potential ability to interact with the 5-hydroxytryptamine(3) (5-HT3) receptor. Most of the new compounds show subnanomolar 5-HT3 receptor affinity. Ester 6bc showing a picomolar K-i value is one of the most potent 5-HT3 receptor ligands so far synthesized. The structure-affinity relationship study suggests the existence of a certain degree of conformational freedom of the amino acid residues interacting with the substituents in positions 3 and 4 of the quipazine quinoline nucleus. Thus, the tacrine-related heterobivalent ligand 6o was designed in an attempt to capitalize on the evidence of such a steric tolerance. Compound 6o shows a nanomolar potency for both the 5-HT3 receptor and the human AChE and represents the first example of a rationally designed high-affinity 5-HT3 receptor ligand showing nanomolar AChE inhibitory activity. Finally, the computational analysis performed on compound 6o allowed the rationalization of the structure-energy determinants for AChE versus BuChE selectivity and revealed the existence of a subsite at the boundary of the 5-HT3 receptor extracellular domain, which could represent a "peripheral" site similar to that evidenced in the AChE gorge.

  DOI：

  10.1021/jm0493461

文献信息

• Certain pyrroloquinolinones; a new class of GABA brain receptor
  申请人：Neurogen Corporation

  公开号：US05908932A1

  公开（公告）日：1999-06-01

  This invention encompasses compounds of formula (I), and pharmaceutically acceptable non-toxic salts thereof wherein X and Y are the same or different and represent oxygen or H.sub.2 with the proviso that not both X and Y are H.sub.2 ; W represents phenyl, thienyl, or pyridyl, each of which may be unsubstituted or mono or disubstituted with organic or inorganic substituents; and R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are variables representing organic and inorganic substituents. These compounds are highly selective agonists, antagonists or inverse agonists for GABAs brain receptors or prodrugs thereof and are useful in the diagnosis and treatment of anxiety, sleep, and seizure disorders, overdose with benzodiazepine drugs, and enhancement of memory.

  本发明涵盖了式（I）的化合物及其药学上可接受的非毒性盐，其中X和Y相同或不同，分别表示氧或H.sub.2，但X和Y不同时为H.sub.2；W表示苯基，噻吩基或吡啶基，每个基团可以是未取代的或有机或无机取代的单个或双个基团；而R.sub.1，R.sub.2，R.sub.3和R.sub.4是代表有机和无机取代基团的变量。这些化合物是高度选择性的GABA脑受体的激动剂，拮抗剂或逆拮抗剂，或它们的前药，可用于诊断和治疗焦虑、睡眠和癫痫障碍、苯二氮卓类药物过量和增强记忆。
• Certain pyrroloquinolinones: a new class of GABA brain receptor ligands
  申请人：Neurogen Corporation

  公开号：US05243049A1

  公开（公告）日：1993-09-07

  This invention encompasses compounds of the formula: ##STR1## and the pharmaceutically acceptable non-toxic salts thereof wherein X and Y are the same or different and represent oxygen or H.sub.2 with the proviso that not both X and Y are H.sub.2 ; W represents phenyl, thienyl, or pyridyl, each of which may be unsubstituted or momo or disubstituted with organic or inorganic substituents; and R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are variables representing organic and inorganic substituents. These compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs thereof and are useful in the diagnosis and treatment of anxiety, sleep, and seizure disorders, overdose with benzodiazepine drugs, and enhancement of memory.

  本发明涵盖以下化合物的公式：##STR1##及其药学上可接受的非毒性盐，其中X和Y相同或不同，代表氧或H.sub.2，但X和Y不同时为H.sub.2; W代表苯基、噻吩基或吡啶基，每种基团可以是未取代的或单取代或双取代的有机或无机基团；而R.sub.1、R.sub.2、R.sub.3和R.sub.4是表示有机和无机取代基的变量。这些化合物是高度选择性的GABAa脑受体激动剂、拮抗剂或反向激动剂，或其前药，并且在焦虑、睡眠和癫痫障碍、苯二氮卓类药物过量和增强记忆的诊断和治疗中有用。
• Certain pyrroloquinolinones; a new class of gaba brain receptor ligands
  申请人：Neurogen Corporation

  公开号：US05604235A1

  公开（公告）日：1997-02-18

  This invention encompasses compounds of formula (I), and pharmaceutically acceptable non-toxic salts thereof wherein X and Y am the same or different and represent oxygen or H.sub.2 with the proviso that not both X and Y are H.sub.2 ; W represents phenyl, thienyl, or pyridyl, each of which may be unsubstituted or mono or disubstituted with organic or inorganic substituents; and R.sub.1, R.sub.2, R.sub.3, and R.sub.4 are variables representing organic and inorganic substituents. These compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs thereof and are useful in the diagnosis and treatment of anxiety, sleep, and seizure disorder overdose with benzodiazepine drugs, and enhancement of memory.

  本发明涵盖了式(I)的化合物及其药学上可接受的非毒性盐，其中X和Y相同或不同，表示氧或H.sub.2，但有一个限制，即X和Y不同时为H.sub.2；W表示苯基、噻吩基或吡啶基，每个基团可以是未取代的或单取代或双取代的有机或无机取代基；R.sub.1、R.sub.2、R.sub.3和R.sub.4是表示有机和无机取代基的变量。这些化合物是高度选择性的GABAa脑受体的激动剂、拮抗剂或反向激动剂或其前药，可用于诊断和治疗焦虑、睡眠和癫痫药物过量的苯二氮卓类药物和增强记忆力。
• US5243049A
  申请人：——

  公开号：US5243049A

  公开（公告）日：1993-09-07
• US5604235A
  申请人：——

  公开号：US5604235A

  公开（公告）日：1997-02-18