4,4a,5,6-tetrahydro-2-(4-methylphenyl)thieno-[2,3-h]cinnolin-3(2H)-one | 119291-81-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4,4a,5,6-tetrahydro-2-(4-methylphenyl)thieno-[2,3-h]cinnolin-3(2H)-one
• 英文别名: 2-(4-Methylphenyl)-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolin-3-one
• CAS: 119291-81-5
• 化学式: C₁₇H₁₆N₂OS
• 分子量: 296.393
• InChiKey: NBYITTNFEXQZSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  60.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,4a,5,6-tetrahydro-2-(4-methylphenyl)thieno-[2,3-h]cinnolin-3(2H)-one 在 氢溴酸 、 二甲基亚砜 作用下， 以 溶剂黄146 为溶剂， 反应 1.5h， 以62%的产率得到2-(4-methylphenyl)-5,6-dihydrothieno-[2,3-h]cinnolin-3(2H)-one
  参考文献：
  名称：

  Synthesis and evaluation of novel 2-aryl-2,5,6,7-tetrahydro-3H-thieno [2′,3′:6,7]cyclohepta[1,2-c]pyridazin-3-ones and 2-aryl-5, 6-dihydrothieno[2,3-h]cinnolin-3(2H)-ones as anxiolytics

  摘要：

  A series of 2-aryl-2,5,6,7-tetrahydro-3H-thieno[2',3':6,7]cyclohepta[1,2-c]pyridazin-3-ones and 2-aryl-5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-ones were synthesized and evaluated for their affinity to benzodiazepine receptors (BZRs) in the excised brain of rats and also for their intrinsic efficacy in augmentation of the gamma-aminobutyric acid-induced chloride currents in the dissociated sensory neurons of frogs. The synthesized compounds showed a high affinity to BZRs. In these compounds, the substituents at the 2-position and at either the 8- or the 9-position and the ring size of the condensed ring affected the biological activity of the compounds. Thus, an introduction of 4-methyl- or 4-chloro-substitute phenyl ring into the 2-position, an introduction of methyl or ethyl into either the 8- or the 9-position, and an expansion of the 6-membered condensed ring to a 7-membered ring brought about a continuous shift of compounds from inverse to full agonists. Among the synthesized compounds, 8-(1 hydroxyethyl)-2-(4-methylphenyl)-5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-one which can be classified as a BZR partial agonist, was found to exhibit an anxio-selective feature.

  DOI：

  10.1016/s0223-5234(97)83286-2
• 作为产物：
  描述：

  2-(6',7'-Dihydrobenzo[b]thiophen-4'(5'H)-on-5'-yl)-acetonitrile 在 盐酸 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 10.0h， 生成 4,4a,5,6-tetrahydro-2-(4-methylphenyl)thieno-[2,3-h]cinnolin-3(2H)-one
  参考文献：
  名称：

  Synthesis and evaluation of novel 2-aryl-2,5,6,7-tetrahydro-3H-thieno [2′,3′:6,7]cyclohepta[1,2-c]pyridazin-3-ones and 2-aryl-5, 6-dihydrothieno[2,3-h]cinnolin-3(2H)-ones as anxiolytics

  摘要：

  A series of 2-aryl-2,5,6,7-tetrahydro-3H-thieno[2',3':6,7]cyclohepta[1,2-c]pyridazin-3-ones and 2-aryl-5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-ones were synthesized and evaluated for their affinity to benzodiazepine receptors (BZRs) in the excised brain of rats and also for their intrinsic efficacy in augmentation of the gamma-aminobutyric acid-induced chloride currents in the dissociated sensory neurons of frogs. The synthesized compounds showed a high affinity to BZRs. In these compounds, the substituents at the 2-position and at either the 8- or the 9-position and the ring size of the condensed ring affected the biological activity of the compounds. Thus, an introduction of 4-methyl- or 4-chloro-substitute phenyl ring into the 2-position, an introduction of methyl or ethyl into either the 8- or the 9-position, and an expansion of the 6-membered condensed ring to a 7-membered ring brought about a continuous shift of compounds from inverse to full agonists. Among the synthesized compounds, 8-(1 hydroxyethyl)-2-(4-methylphenyl)-5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-one which can be classified as a BZR partial agonist, was found to exhibit an anxio-selective feature.

  DOI：

  10.1016/s0223-5234(97)83286-2

文献信息

• Fused pyridazine compound
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：US05597918A1

  公开（公告）日：1997-01-28

  A fused pyridazine compound of the formula ##STR1## wherein each symbol is as defined in the description. The compounds of the present invention are useful as anxiolytic agents which selectively act on anxiety because of having less side effects (e.g. muscle-relaxation, sedation or interaction with alcohol/barbiturates).

  一种具有以下结构式的融合吡啶并化合物##STR1##，其中描述中所定义的每个符号。本发明的化合物可作为抗焦虑剂使用，因为其具有较少的副作用（例如肌肉松弛、镇静或与酒精/巴比妥类药物的相互作用），能够选择性地作用于焦虑。
• FUSED PYRIDAZINE COMPOUND AND PHARMACEUTICAL USE THEREOF
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0601184A1

  公开（公告）日：1994-06-15

  A fused pyridazine compound represented by the general formula (I) and an antianxiety drug containing the same as the active ingredient: wherein R¹ represents carboxyl, formyl, cyano, hydroxy-iminomethyl, acyl, etc.; R² represents hydrogen, C₁ to C₈ alkyl, hydroxyalkyl, alkanoyloxyalkyl, aryl, aralkyl, heteroaryl, etc.; A represents sulfur or -CH=CH-; E represents -CH₂- or -S(O)m-, wherein m represents 0, 1 or 2; n represents 1 or 2; and the bond represented by both solid and broken lines is either a single or a double bond; provided that when A represents sulfur, E represents -CH₂-, while when A represents -CH=CH-, E represents -S(O)m-, wherein m represents 0, 1 or 2, and n represents 2. This compound is reduced in side effects such as muscular relaxation, anesthesia potentiation, sedation, sleep/alcohol potentiation, etc., thus being useful as an antianxiety drug which selectively acts against anxiety.

  一种由通式(I)代表的融合哒嗪化合物和一种以其为有效成分的抗焦虑药物： 其中R¹代表羧基、甲酰基、氰基、羟基亚氨甲基、酰基等；R²代表氢、C₁至C₈烷基、羟基烷基、烷酰氧基烷基、芳基、芳烷基、杂芳基等。A代表硫或-CH＝CH-；E代表-CH₂-或-S(O)m-，其中m代表0、1或2；n代表1或2；实线和断线所代表的键为单键或双键；条件是当A代表硫时，E代表-CH₂-，而当A代表-CH＝CH-时，E代表-S(O)m-，其中m代表0、1或2，n代表2。这种化合物可减少副作用，如肌肉松弛、麻醉增效、镇静、睡眠/酒精增效等，因此可作为抗焦虑药物，选择性地对抗焦虑。
• HAKAO, TATSU;MORITA, KEHNDZI;KURU, MASAO;TAKEHXARA, SYUDZO
  作者：HAKAO, TATSU、MORITA, KEHNDZI、KURU, MASAO、TAKEHXARA, SYUDZO

  DOI：——

  日期：——
• US5597918A
  申请人：——

  公开号：US5597918A

  公开（公告）日：1997-01-28
• Synthesis and evaluation of novel 2-aryl-2,5,6,7-tetrahydro-3H-thieno [2′,3′:6,7]cyclohepta[1,2-c]pyridazin-3-ones and 2-aryl-5, 6-dihydrothieno[2,3-h]cinnolin-3(2H)-ones as anxiolytics
  作者：H Tanaka、S Kirihara、H Yasumatsu、T Yakushiji、T Nakao

  DOI：10.1016/s0223-5234(97)83286-2

  日期：1997.7

  A series of 2-aryl-2,5,6,7-tetrahydro-3H-thieno[2',3':6,7]cyclohepta[1,2-c]pyridazin-3-ones and 2-aryl-5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-ones were synthesized and evaluated for their affinity to benzodiazepine receptors (BZRs) in the excised brain of rats and also for their intrinsic efficacy in augmentation of the gamma-aminobutyric acid-induced chloride currents in the dissociated sensory neurons of frogs. The synthesized compounds showed a high affinity to BZRs. In these compounds, the substituents at the 2-position and at either the 8- or the 9-position and the ring size of the condensed ring affected the biological activity of the compounds. Thus, an introduction of 4-methyl- or 4-chloro-substitute phenyl ring into the 2-position, an introduction of methyl or ethyl into either the 8- or the 9-position, and an expansion of the 6-membered condensed ring to a 7-membered ring brought about a continuous shift of compounds from inverse to full agonists. Among the synthesized compounds, 8-(1 hydroxyethyl)-2-(4-methylphenyl)-5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-one which can be classified as a BZR partial agonist, was found to exhibit an anxio-selective feature.