2-(1,2,3,4-tetrahydro-7-nitro-1-oxonaphthalen-2-yl)acetic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(1,2,3,4-tetrahydro-7-nitro-1-oxonaphthalen-2-yl)acetic acid
• 英文别名: 7-nitro-1,2,3,4-tetrahydro-1-oxo-2-naphthaleneacetic acid；2-(7-nitro-1-oxo-3,4-dihydro-2H-naphthalen-2-yl)acetic acid
• 化学式: C₁₂H₁₁NO₅
• 分子量: 249.223
• InChiKey: LFZCJXLKPNTIFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(1,2,3,4-tetrahydro-7-nitro-1-oxonaphthalen-2-yl)acetic acid 在 1-羟基苯并三唑 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 16.25h， 生成 2-(1,1-ethylenedioxy-1,2,3,4-tetrahydro-7-nitronaphthalen-2-yl)-1-[4-(2-methoxyphenyl)piperazin-1-yl]ethanone
  参考文献：
  名称：

  Synthesis and biological evaluation of a series of aminoalkyl-tetralones and tetralols as dual dopamine/serotonin ligands

  摘要：

  A series of novel alpha-tetralone and a-tetralol derivatives was synthesized, and their binding affinities for 5-HT2A and D-2 receptors, the most important targets implicated in the anti-schizophrenia drug action, were evaluated to elucidate how substitutions in the aromatic ring of the pharmacophore affect to the affinity or selectivity for these receptors. The replacement of the H-7 in the tetrahydronaphthalene system by an amino group resulted in privileged 5-HT2A affinity of the 6-fluorobenzo[d]isoxazol derivative 36 and the alcohol 25 both showing a pK(i) value for 5-HT2A higher than 8.3 and good binding affinities for D-2 receptor leading to a Meltzer's ratio characteristic of an atypical antipsychotic profile. Additionally, a small collection of 3-aminomethyltetralone derivatives was prepared and examined here for their affinities and selectivities as 5-HT2A/D-2 dual ligands. Compound 11 shows the best profile with good pK(i) values for 5-HT2A and D-2 receptors leading to a Meltzer's ratio characteristic of a typical antipsychotic behaviour. These three compounds behaved as competitive antagonists of both 5-HT2A and D-2 receptors, and might be promising pharmacological tools for the investigation of the dual function of the 5HT(2A)-D-2 ligands. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.066
• 作为产物：
  描述：

  7-硝基-3,4-二氢-2H-1-萘酮 在 对甲苯磺酸 、 溶剂黄146 、 锌 作用下， 以 水 为溶剂， 反应 2.0h， 生成 2-(1,2,3,4-tetrahydro-7-nitro-1-oxonaphthalen-2-yl)acetic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of a series of aminoalkyl-tetralones and tetralols as dual dopamine/serotonin ligands

  摘要：

  A series of novel alpha-tetralone and a-tetralol derivatives was synthesized, and their binding affinities for 5-HT2A and D-2 receptors, the most important targets implicated in the anti-schizophrenia drug action, were evaluated to elucidate how substitutions in the aromatic ring of the pharmacophore affect to the affinity or selectivity for these receptors. The replacement of the H-7 in the tetrahydronaphthalene system by an amino group resulted in privileged 5-HT2A affinity of the 6-fluorobenzo[d]isoxazol derivative 36 and the alcohol 25 both showing a pK(i) value for 5-HT2A higher than 8.3 and good binding affinities for D-2 receptor leading to a Meltzer's ratio characteristic of an atypical antipsychotic profile. Additionally, a small collection of 3-aminomethyltetralone derivatives was prepared and examined here for their affinities and selectivities as 5-HT2A/D-2 dual ligands. Compound 11 shows the best profile with good pK(i) values for 5-HT2A and D-2 receptors leading to a Meltzer's ratio characteristic of a typical antipsychotic behaviour. These three compounds behaved as competitive antagonists of both 5-HT2A and D-2 receptors, and might be promising pharmacological tools for the investigation of the dual function of the 5HT(2A)-D-2 ligands. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.10.066

文献信息

• Benzo[h]cinnoline compound, a method of preparing said compound and a
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：US04782057A1

  公开（公告）日：1988-11-01

  A benzo[h]cinnoline compound of the formula: ##STR1## wherein each of X and Y is hydrogen, halogen, trifluoromethyl, hydroxy, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, amino, alkanoylamido having 2 to 4 carbon atoms, nitro, cyano, alkanoyl having 2 to 4 carbon atoms; Ar is phenyl or pyridyl which may be optionally substituted by at least one substituent selected from the group consisting of halogen, trifluoromethyl, hydroxy, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, amino, alkanoylamido having 2 to 4 carbon atoms, nitro and cyano; and the bond position indicated by dotted line is single bond or double bond, a method of preparing said compound and a pharmaceutical composition containing said compound. Since these compounds possess high affinity for benzodiazepine receptor and antianxiety activity, they are useful as neutralizers to an excess dose of antianxiety agents or as antianxiety agents.

  一种苯并[h]茚啉化合物，其化学式为：##STR1## 其中X和Y分别为氢，卤素，三氟甲基，羟基，具有1至4个碳原子的烷基，具有1至4个碳原子的烷氧基，氨基，具有2至4个碳原子的烷酰胺基，硝基，氰基，具有2至4个碳原子的烷酰基；Ar为苯基或吡啶基，可以选择性地被至少一个取代基取代，所述取代基从卤素，三氟甲基，羟基，具有1至4个碳原子的烷基，具有1至4个碳原子的烷氧基，氨基，具有2至4个碳原子的烷酰胺基，硝基和氰基中选择；虚线所示的键位为单键或双键，制备该化合物的方法以及含有该化合物的制药组合物。由于这些化合物具有高亲和力的苯二氮平受体和抗焦虑活性，它们可用作抗焦虑剂的中和剂或抗焦虑剂。
• BENZO ADh BDCINNOLINE COMPOUNDS, PROCESS FOR THEIR PREPARATION, AND MECIDINAL COMPOSITION CONTAINING THEM
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：EP0190367A1

  公开（公告）日：1986-08-13

  Benzo[h]cinnoline compounds represented by general formula (I) wherein X and Y each represents hydrogen, halogen, trifluoromethyl, hydroxy, C1-4 alkyl, C1-4alkoxy, amino, C2-4 alkanoylamido, nitro, cyano, or C2-4 alkanoyl, Ar represents phenyl or pyridyl optionally having at least one of halogen, trifluoromethyl, hydroxy, C1-4 alkyl, C1-4 alkoxy, amino, C2-4 alkanoylamido, nitro, and cyano, and dotted line represents a single or double bond), a process for their preparation, and a medicinal composition containing them. These compounds possess a strong affinity for benzodiazepine receptor and an anti-anxiety effect and are therefore useful for neutralizing excess administration anti-anxiety agents or as an anti-anxiety agent itself.

  由通式(I)代表的苯并[h]噌啉化合物 其中 X 和 Y 分别代表氢、卤素、三氟甲基、羟基、C1-4 烷基、C1-4 烷氧基、氨基、C2-4 烷酰氨基、硝基、氰基或 C2-4 烷酰基，Ar 代表苯基或吡啶基，任选地具有卤素、三氟甲基、羟基、C1-4 烷基、C1-4 烷氧基、氨基、C2-4 烷酰氨基、硝基和氰基中的至少一种，虚线代表单键或双键）、三氟甲基、羟基、C1-4 烷基、C1-4 烷氧基、氨基、C2-4 烷酰基氨基、硝基和氰基，虚线代表单键或双键）、其制备方法以及含有它们的药物组合物。这些化合物对苯二氮卓受体有很强的亲和力，并具有抗焦虑作用，因此可用于中和过量服用的抗焦虑剂或作为抗焦虑剂本身。
• US4782057A
  申请人：——

  公开号：US4782057A

  公开（公告）日：1988-11-01
• Synthesis and biological evaluation of a series of aminoalkyl-tetralones and tetralols as dual dopamine/serotonin ligands
  作者：Laura Carro、María Torrado、Enrique Raviña、Christian F. Masaguer、Sonia Lage、José Brea、María I. Loza

  DOI：10.1016/j.ejmech.2013.10.066

  日期：2014.1

  A series of novel alpha-tetralone and a-tetralol derivatives was synthesized, and their binding affinities for 5-HT2A and D-2 receptors, the most important targets implicated in the anti-schizophrenia drug action, were evaluated to elucidate how substitutions in the aromatic ring of the pharmacophore affect to the affinity or selectivity for these receptors. The replacement of the H-7 in the tetrahydronaphthalene system by an amino group resulted in privileged 5-HT2A affinity of the 6-fluorobenzo[d]isoxazol derivative 36 and the alcohol 25 both showing a pK(i) value for 5-HT2A higher than 8.3 and good binding affinities for D-2 receptor leading to a Meltzer's ratio characteristic of an atypical antipsychotic profile. Additionally, a small collection of 3-aminomethyltetralone derivatives was prepared and examined here for their affinities and selectivities as 5-HT2A/D-2 dual ligands. Compound 11 shows the best profile with good pK(i) values for 5-HT2A and D-2 receptors leading to a Meltzer's ratio characteristic of a typical antipsychotic behaviour. These three compounds behaved as competitive antagonists of both 5-HT2A and D-2 receptors, and might be promising pharmacological tools for the investigation of the dual function of the 5HT(2A)-D-2 ligands. (C) 2013 Elsevier Masson SAS. All rights reserved.