ethyl 2-((3-cyano-4-methyl-6-oxo-1,6-dihydropyridin-2-yl)thio)acetate | 134616-74-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: ethyl 2-((3-cyano-4-methyl-6-oxo-1,6-dihydropyridin-2-yl)thio)acetate
• 英文别名: Ethyl [(3-cyano-4-methyl-6-oxo-1,6-dihydro-2-pyridinyl)thio]acetate；ethyl 2-[(3-cyano-4-methyl-6-oxo-1H-pyridin-2-yl)sulfanyl]acetate
• CAS: 134616-74-3
• 化学式: C₁₁H₁₂N₂O₃S
• 分子量: 252.294
• InChiKey: FAEKWVWUOBWWOA-UHFFFAOYSA-N

物化性质

• 熔点：
  137 °C(Solv: ethanol (64-17-5))
• 沸点：
  398.8±42.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-((3-cyano-4-methyl-6-oxo-1,6-dihydropyridin-2-yl)thio)acetate 在 盐酸 、 N-氯代丁二酰亚胺 、 potassium carbonate 作用下， 以 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 41.75h， 生成 ethyl 6-butoxy-5-chloro-3-(1,3-dioxoisoindolin-2-yl)-4-methylthieno[2,3-b]pyridine-2-carboxylate
  参考文献：
  名称：

  A structure–activity relationship study of the positive allosteric modulator LY2033298 at the M₄ muscarinic acetylcholine receptor

  摘要：

  靶向M4肌酸乙酰胆碱受体的阳性变构调节剂通过其新颖的作用方式，相较于传统的正交配体，提供更高的亚型选择性和作为中枢神经系统药物的独特潜力。

  DOI：

  10.1039/c5md00334b
• 作为产物：
  描述：

  morpholinium 3-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-thiolate 在 盐酸 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 ethyl 2-((3-cyano-4-methyl-6-oxo-1,6-dihydropyridin-2-yl)thio)acetate
  参考文献：
  名称：

  Structure–Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D₂ Receptor

  摘要：

  Biased agonism at GPCRs highlights the potential for the discovery and design of pathway-selective ligands and may confer therapeutic advantages to ligands targeting the dopamine D-2 receptor (D2R). We investigated the determinants of efficacy, affinity, and bias for three privileged structures for the D2R, exploring changes to linker length and incorporation of a heterocyclic unit. Profiling the compounds in two signaling assays (cAMP and pERK1/2) allowed us to identify and quantify determinants of biased agonism at the D2R. Substitution on the phenylpiperazine privileged structures (2-methoxy vs 2,3-dichloro) influenced bias when the thienopyridine heterocycle was absent. Upon inclusion of the thienopyridine unit, the substitution pattern (4,6-dimethyl vs 5-chloro-6-methoxy-4-methyl) had a significant effect on bias that overruled the effect of the phenylpiperazine substitution pattern. This latter observation could be reconciled with an extended binding mode for these compounds, whereby the interaction of the heterocycle with a secondary binding pocket may engender bias.

  DOI：

  10.1021/jm500457x

文献信息

• Dyachenko, V. D.; Sharanin, Yu. A.; Shestopalov, A. M., Journal of general chemistry of the USSR, 1990, vol. 60, # 10, p. 2131 - 2138
  作者：Dyachenko, V. D.、Sharanin, Yu. A.、Shestopalov, A. M.、Rodinovskaya, L. A.、Turov, A. V.、et al.

  DOI：——

  日期：——
• DYACHENKO, V. D.;SHARANIN, YU. A.;SHESTOPALOV, A. M.;RODINOVSKAYA, L. A.;+, ZH. OBSHCH. XIMII, 60,(1990) N0, S. 2384-2392
  作者：DYACHENKO, V. D.、SHARANIN, YU. A.、SHESTOPALOV, A. M.、RODINOVSKAYA, L. A.、+

  DOI：——

  日期：——
• A structure–activity relationship study of the positive allosteric modulator LY2033298 at the M₄ muscarinic acetylcholine receptor
  作者：Monika Szabo、Tracey Huynh、Celine Valant、J. Robert Lane、Patrick M. Sexton、Arthur Christopoulos、Ben Capuano

  DOI：10.1039/c5md00334b

  日期：——

  Positive allosteric modulators targeting the M₄ muscarinic acetylcholine receptor offer greater sub-type selectivity and unique potential as CNS agents through their novel mode of action to traditional orthosteric ligands.

  靶向M4肌酸乙酰胆碱受体的阳性变构调节剂通过其新颖的作用方式，相较于传统的正交配体，提供更高的亚型选择性和作为中枢神经系统药物的独特潜力。
• Structure–Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D₂ Receptor
  作者：Monika Szabo、Carmen Klein Herenbrink、Arthur Christopoulos、J. Robert Lane、Ben Capuano

  DOI：10.1021/jm500457x

  日期：2014.6.12

  Biased agonism at GPCRs highlights the potential for the discovery and design of pathway-selective ligands and may confer therapeutic advantages to ligands targeting the dopamine D-2 receptor (D2R). We investigated the determinants of efficacy, affinity, and bias for three privileged structures for the D2R, exploring changes to linker length and incorporation of a heterocyclic unit. Profiling the compounds in two signaling assays (cAMP and pERK1/2) allowed us to identify and quantify determinants of biased agonism at the D2R. Substitution on the phenylpiperazine privileged structures (2-methoxy vs 2,3-dichloro) influenced bias when the thienopyridine heterocycle was absent. Upon inclusion of the thienopyridine unit, the substitution pattern (4,6-dimethyl vs 5-chloro-6-methoxy-4-methyl) had a significant effect on bias that overruled the effect of the phenylpiperazine substitution pattern. This latter observation could be reconciled with an extended binding mode for these compounds, whereby the interaction of the heterocycle with a secondary binding pocket may engender bias.