ethyl 2-(3-methyl-1,2,4-thiadiazol-5-yl)acetate | 40929-69-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 2-(3-methyl-1,2,4-thiadiazol-5-yl)acetate
• CAS: 40929-69-9
• 化学式: C₇H₁₀N₂O₂S
• 分子量: 186.235
• InChiKey: BHXGSJHGWHYMMY-UHFFFAOYSA-N

物化性质

• 沸点：
  297.5±42.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  80.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-(3-methyl-1,2,4-thiadiazol-5-yl)acetate 在 sodium methylate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 3-(4-Methoxy-phenyl)-1-methyl-5-(3-methyl-[1,2,4]thiadiazol-5-yl)-1H-[2,4']bipyridinyl-6-one
  参考文献：
  名称：

  3-Heteroaryl-2-pyridones:  Benzodiazepine Site Ligands with Functional Selectivity for α2/α3-Subtypes of Human GABA_A Receptor-Ion Channels

  摘要：

  A novel series of 3-heteroaryl-5,6-bis(aryl)-1-methyl-2-pyridones were developed with high affinity for the benzodiazepine (BZ) binding site of human gamma-aminobutyric acid (GABA(A)) receptor ion channels, low binding selectivity for alpha2- and/or alpha3- over alpha1-containing GABA(A) receptor subtypes and high binding selectivity over alpha5 subtypes. High affinity appeared to be associated with a coplanar conformation of the pyridone and sulfur-containing 3-heteroaryl rings resulting from an attractive S...O intramolecular interaction. Functional selectivity (i.e., selective efficacy) for alpha2 and/or alpha3 GABA(A) receptor subtypes over alpha1 was observed in several of these compounds in electrophysiological assays. Furthermore, an alpha3 subtype selective inverse agonist was proconvulsant and anxiogenic in rodents while an alpha2/alpha3 subtype selective partial agonist was anticonvulsant and anxiolytic, supporting the hypothesis that subtype selective BZ site agonists may provide new anxiolytic therapies.

  DOI：

  10.1021/jm0110789
• 作为产物：
  描述：

  5-氯-3-甲基-1,2,4-噻唑 、 乙酸乙酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以9%的产率得到ethyl 2-(3-methyl-1,2,4-thiadiazol-5-yl)acetate
  参考文献：
  名称：

  3-Heteroaryl-2-pyridones:  Benzodiazepine Site Ligands with Functional Selectivity for α2/α3-Subtypes of Human GABA_A Receptor-Ion Channels

  摘要：

  A novel series of 3-heteroaryl-5,6-bis(aryl)-1-methyl-2-pyridones were developed with high affinity for the benzodiazepine (BZ) binding site of human gamma-aminobutyric acid (GABA(A)) receptor ion channels, low binding selectivity for alpha2- and/or alpha3- over alpha1-containing GABA(A) receptor subtypes and high binding selectivity over alpha5 subtypes. High affinity appeared to be associated with a coplanar conformation of the pyridone and sulfur-containing 3-heteroaryl rings resulting from an attractive S...O intramolecular interaction. Functional selectivity (i.e., selective efficacy) for alpha2 and/or alpha3 GABA(A) receptor subtypes over alpha1 was observed in several of these compounds in electrophysiological assays. Furthermore, an alpha3 subtype selective inverse agonist was proconvulsant and anxiogenic in rodents while an alpha2/alpha3 subtype selective partial agonist was anticonvulsant and anxiolytic, supporting the hypothesis that subtype selective BZ site agonists may provide new anxiolytic therapies.

  DOI：

  10.1021/jm0110789

文献信息

• [EN] TRICYCLIC PYRIDIN-2-ONE ANALOGUES AS LIGANDS FOR GABA-A RECEPTORS<br/>[FR] ANALOGUES DE PYRIDINE-2-ONE TRICYCLIQUE UTILES EN TANT QUE LIGANDS POUR LES RECEPTEURS GABA-A
  申请人：MERCK SHARP & DOHME

  公开号：WO2003016311A1

  公开（公告）日：2003-02-27

  A class of selectively substituted fused tricyclic compounds based on a substituted pyridinone moiety are potent and functionally selective ligands for the α2/α3 subunit of the human GABA-A receptor and are thereby effective in the treatment of anxiety. The present invention provides a compound of formula (I), or a salt or N-oxide thereof: wherein E represents -(CH2)n-; n is 1, 2 or 3; R1 represents aryl, C¿3-7? heterocycloalkyl, C3-7 heterocycloalkenyl or heteroaryl, any of which groups may be optionally substituted; or halogen, -NHCOR?3, -COR3¿ or CO¿2R?3; R2 represents aryl or heteroaryl, either of which groups may be optionally substituted; and R3 represents C¿3-6? alkyl, hydroxy(C1-6)alkyl, C2-6 alkenyl, C3-7 cycloalkyl, aryl, aryl(C1-6)alkyl, heteroaryl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted; said optional substitutents on R?1, R2 and R3¿ being independently selected from C¿1-6? alkyl, halo(C1-6)alkyl, C3-7 cycloalkyl, halogen, formyl and C2-6 alkylcarbonyl; excluding compounds in which R?1¿ represents methylthiazolyl or hydroxymethylthiazolyl.