Potassium; 4-oxo-3,4,5,6,7,8-hexahydro-benzo[4,5]thieno[2,3-d]pyrimidine-2-thiolate | 53162-03-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: Potassium; 4-oxo-3,4,5,6,7,8-hexahydro-benzo[4,5]thieno[2,3-d]pyrimidine-2-thiolate
• 英文别名: potassium;2-sulfanylidene-5,6,7,8-tetrahydro-3H-[1]benzothiolo[2,3-d]pyrimidin-4-olate
• CAS: 53162-03-1
• 化学式: C₁₀H₉N₂OS₂*K
• 分子量: 276.425
• InChiKey: FZJWHXFAHJGLAZ-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.23
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  70.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Potassium; 4-oxo-3,4,5,6,7,8-hexahydro-benzo[4,5]thieno[2,3-d]pyrimidine-2-thiolate 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 1,2,3,4,5,6,7,8-八氢苯并[4,5]噻吩并[2,3-d]嘧啶-2,4-二酮
  参考文献：
  名称：

  [[（（芳基哌嗪基）烷基]硫代]噻吩并[2,3-d]嘧啶酮衍生物为高亲和力的选择性5-HT1A受体配体。

  摘要：

  一系列2-[[（（4-芳基-1-哌嗪基）烷基]硫代]噻吩并[2,3-d]嘧啶-4（1H）-和3-取代的2-[[（（4-芳基-1）制备了-哌嗪基）烷基]硫代]噻吩并[2,3-d]嘧啶-4（3H）-衍生物，并通过放射性配体结合试验评估了其在体外对5-HT1A受体的亲和力。还检查了5-HT1A受体而不是α1-肾上腺素受体的选择性（IC50α1与IC50 5-HT1A之比）。结合测试表明了[（芳基哌嗪基）烷基]硫基部分的最佳特征以及有效和选择性的5-HT1A配体的噻吩和嘧啶酮环上的取代基。从大鼠海马膜上置换[3H] -8-OH-DPAT的最有效衍生物是3-氨基-2-[[3- [4-（2-（2-甲氧基苯基）-1-哌嗪基]丙基]硫基] -5 ，6-二甲基噻吩并[2,3-d]嘧啶-4（3H）-一（70）（IC50 = 0。3 nM），对5-HT1A的选择性比α1-肾上腺素能受体高24。N4哌嗪环上的2-

  DOI：

  10.1021/jm950866t
• 作为产物：
  描述：

  ethyl 2-(3-benzoylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 在 氢氧化钾 作用下， 生成 Potassium; 4-oxo-3,4,5,6,7,8-hexahydro-benzo[4,5]thieno[2,3-d]pyrimidine-2-thiolate
  参考文献：
  名称：

  Zekany; Makleit, Pharmazie, 1987, vol. 42, # 3, p. 160 - 161

  摘要：

  DOI：

文献信息

• Discovery of a Novel 5-HT₃ Antagonist/5-HT_1A Agonist 3-Amino-5,6,7,8-tetrahydro-2-{4-[4-(quinolin-2-yl)piperazin-1-yl]butyl}quinazolin-4(3<i>H</i>)-one (TZB-30878) as an Orally Bioavailable Agent for Irritable Bowel Syndrome
  作者：Akira Asagarasu、Teruaki Matsui、Hiroyuki Hayashi、Satoru Tamaoki、Yukinao Yamauchi、Kouichi Minato、Michitaka Sato

  DOI：10.1021/jm1002292

  日期：2010.11.11

  We have prepared a series of quinazolinone derivatives linked with piperazinylquinoline for the treatment of irritable bowel syndrome (IBS). Using pharmacophore analysis, we designed and synthesized compounds which bind to both serotonin receptor subtype 1A (5-HT1A) and subtype 3 (5-HT3). Quinazolinone derivatives with a sulfur atom in the linker showed high affinity in in vitro assays, but low in vivo activity. Focusing on the linker to improve the pharmacokinetic profile, the sulfur atom in the linker was replaced with a methylene group. Further optimization led to the discovery of compound 17m (TZB-30878) (J. Pharmacol. Exp. Ther. 2007, 322, 1315-1323, Patent WO2005082887 (A1), 2005), a novel 5-HT1A agonist/5-HT3 antagonist in the 3-aminoquinazolinone series. In in vivo functional assays, 17m dose dependently inhibited the Bezold-Jarisch reflex and induced 5-HT1A-mediated behaviors, and in an IBS animal model, 17m significantly inhibited stress-induced defecation. Pretreatment by WAY-100635 (5-HT1A antagonist) significantly attenuated but did not abolish the inhibitory effects of 17m. These results suggested that 17m exerted inhibitory effects via both 5-HT1A agonistic and 5-HT3 antagonistic activities and that 17m would be useful as a therapeutic agent for IBS.
• Vas'kevich; Khripak; Staninets, Russian Journal of Organic Chemistry, 2000, vol. 36, # 7, p. 1061 - 1066
  作者：Vas'kevich、Khripak、Staninets、Zborovskii、Chernega

  DOI：——

  日期：——