methyl [2-(cyanoacetyl)-4-methylphenyl]dithiocarbamate | 1190085-08-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl [2-(cyanoacetyl)-4-methylphenyl]dithiocarbamate
• 英文别名: methyl N-[2-(2-cyanoacetyl)-4-methylphenyl]carbamodithioate
• CAS: 1190085-08-5
• 化学式: C₁₂H₁₂N₂OS₂
• 分子量: 264.372
• InChiKey: ZKIVUILSJUARRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl [2-(cyanoacetyl)-4-methylphenyl]dithiocarbamate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以97%的产率得到4-hydroxy-6-methyl-2-thioxo-1,2-dihydroquinoline-3-carbonitrile
  参考文献：
  名称：

  3-Alkyl- and 3-amido-isothiazoloquinolin-4-ones as ligands for the benzodiazepine site of GABAA receptors

  摘要：

  Based on a pharmacophore model of the benzodiazepine binding site of the GABA(A) receptors, developed with synthetic flavones and potent 3-carbonylquinolin-4-ones, 3-alkyl- and 3-amido-6-methylisothiazoloquinolin-4-ones were designed, prepared and assayed. The suggestion that the interaction between the hydrogen bond donor site H1 with the 3-carbonyl oxygen in 3-carbonylquinolin-4-ones can be replaced by an interaction between H1 and N-2 in the isothiazoloquinolin-4-ones, was confirmed. As with the 3-carbonylquinolin-4-ones, the length of the chain in position 3 is critical for an efficient interaction with the lipophilic pockets of the pharmacophore model. The most potent 3-alkyl derivative, 3-pentyl-6-methylisothiazoloquinolin-4-one, has an affinity (K-i value) for the benzodiazepine binding site of the GABA(A) receptors of 13 nM. However, by replacing the 3-pentyl with a 3-butyramido group an even more potent compound was obtained, with a K-i value of 2.8 nM, indicating that the amide function facilitates additional interactions with the binding site. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2011.10.001
• 作为产物：
  描述：

  2-氨基-5-甲基苯甲酸 在 乙酸酐 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 为溶剂， 反应 21.0h， 生成 methyl [2-(cyanoacetyl)-4-methylphenyl]dithiocarbamate
  参考文献：
  名称：

  3-Alkyl- and 3-amido-isothiazoloquinolin-4-ones as ligands for the benzodiazepine site of GABAA receptors

  摘要：

  Based on a pharmacophore model of the benzodiazepine binding site of the GABA(A) receptors, developed with synthetic flavones and potent 3-carbonylquinolin-4-ones, 3-alkyl- and 3-amido-6-methylisothiazoloquinolin-4-ones were designed, prepared and assayed. The suggestion that the interaction between the hydrogen bond donor site H1 with the 3-carbonyl oxygen in 3-carbonylquinolin-4-ones can be replaced by an interaction between H1 and N-2 in the isothiazoloquinolin-4-ones, was confirmed. As with the 3-carbonylquinolin-4-ones, the length of the chain in position 3 is critical for an efficient interaction with the lipophilic pockets of the pharmacophore model. The most potent 3-alkyl derivative, 3-pentyl-6-methylisothiazoloquinolin-4-one, has an affinity (K-i value) for the benzodiazepine binding site of the GABA(A) receptors of 13 nM. However, by replacing the 3-pentyl with a 3-butyramido group an even more potent compound was obtained, with a K-i value of 2.8 nM, indicating that the amide function facilitates additional interactions with the binding site. (C) 2011 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2011.10.001

文献信息

• [EN] NEW CLASSES OF GABAa/BZR LIGANDS<br/>[FR] NOUVELLES CLASSES DE LIGANDS GABAA/BZR
  申请人：FORSKARPATENT I SYD AB

  公开号：WO2009123536A1

  公开（公告）日：2009-10-08

  The present invention relates to novel GABAA/BzR ligands of the general formulas (I), (II) and (III) wherein R1 is selected from the group consisting of hydrogen, halogen, haloalkyl having 1-2 carbon atoms, alkoxy having 1 to 3 carbon atoms in the alkyl chain, alkyl having 1 to 3 carbon atoms, and nitro, and R2 is selected from the group consisting of hydrogen, halogen and alkyl having 1 to 2 carbon atoms, as well as the use of these compounds for treating anxiolytic, anticonvulsant, sedative- hypnotic and myorelaxant conditions as well as anxiogenic, somnolytic and convulsant conditions in mammals including pharmaceutical compositions comprising the same

  本发明涉及一种新型的GABAA/BzR配体，其一般式为(I)、(II)和(III)，其中R1从氢、卤素、具有1-2个碳原子的卤代烷基、在烷基链中具有1-3个碳原子的烷氧基、具有1-3个碳原子的烷基和硝基组成的群中选择，R2从氢、卤素和具有1-2个碳原子的烷基组成的群中选择，以及利用这些化合物治疗哺乳动物中的抗焦虑、抗惊厥、镇静催眠和肌松条件，以及包括这些化合物的药物组合物。
• NEW CLASSES OF GABAA/BZR LIGANDS
  申请人：Nielsen Mogens

  公开号：US20110105553A1

  公开（公告）日：2011-05-05

  The present invention relates to novel GABA A /BzR ligands of the general formulas (I), (II) and (III) wherein R 1 is selected from the group consisting of hydrogen, halogen, haloalkyl having 1-2 carbon atoms, alkoxy having 1 to 3 carbon atoms in the alkyl chain, alkyl having 1 to 3 carbon atoms, and nitro, and R 2 is selected from the group consisting of hydrogen, halogen and alkyl having 1 to 2 carbon atoms, as well as the use of these compounds for treating anxiolytic, anticonvulsant, sedative-hypnotic and myorelaxant conditions as well as anxiogenic, somnolytic and convulsant conditions in mammals including pharmaceutical compositions comprising the same

  本发明涉及一种新型GABAA/BzR配体，其通式为(I)、(II)和(III)，其中R1选自氢、卤素、具有1-2个碳原子的卤代烷基、具有1-3个碳原子的烷氧基、具有1-3个碳原子的烷基和硝基的群体，R2选自氢、卤素和具有1-2个碳原子的烷基的群体，以及使用这些化合物治疗哺乳动物的抗焦虑、抗惊厥、镇静催眠和肌松作用症状，以及包括这些化合物的制药组合物。
• US8481561B2
  申请人：——

  公开号：US8481561B2

  公开（公告）日：2013-07-09
• 3-Alkyl- and 3-amido-isothiazoloquinolin-4-ones as ligands for the benzodiazepine site of GABAA receptors
  作者：Jakob Nilsson、Elsebet Østergaard Nielsen、Tommy Liljefors、Mogens Nielsen、Olov Sterner

  DOI：10.1016/j.bioorg.2011.10.001

  日期：2012.2

  Based on a pharmacophore model of the benzodiazepine binding site of the GABA(A) receptors, developed with synthetic flavones and potent 3-carbonylquinolin-4-ones, 3-alkyl- and 3-amido-6-methylisothiazoloquinolin-4-ones were designed, prepared and assayed. The suggestion that the interaction between the hydrogen bond donor site H1 with the 3-carbonyl oxygen in 3-carbonylquinolin-4-ones can be replaced by an interaction between H1 and N-2 in the isothiazoloquinolin-4-ones, was confirmed. As with the 3-carbonylquinolin-4-ones, the length of the chain in position 3 is critical for an efficient interaction with the lipophilic pockets of the pharmacophore model. The most potent 3-alkyl derivative, 3-pentyl-6-methylisothiazoloquinolin-4-one, has an affinity (K-i value) for the benzodiazepine binding site of the GABA(A) receptors of 13 nM. However, by replacing the 3-pentyl with a 3-butyramido group an even more potent compound was obtained, with a K-i value of 2.8 nM, indicating that the amide function facilitates additional interactions with the binding site. (C) 2011 Elsevier Inc. All rights reserved.