(R,S)-ethyl 2-(isothiocyanato)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate | 257610-92-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: (R,S)-ethyl 2-(isothiocyanato)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
• 英文别名: ethyl 2-isothiocyanato-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate；Ethyl 2-isothiocyanato-4-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate
• CAS: 257610-92-7
• 化学式: C₁₃H₁₅NO₂S₂
• 分子量: 281.4
• InChiKey: GNEFIWCVUDZEJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  99
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R,S)-ethyl 2-(isothiocyanato)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 4.0h， 生成 5-methyl-3-phenyl-2-sulfanyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one
  参考文献：
  名称：

  C-8-叔丁基取代的4-芳基-6,7,8,9-四氢苯并[4,5]噻吩并[3,2- e ] [1,2,4]三唑[4,3]的肠病毒抑制活性-一个]嘧啶-5-（4 ħ） -酮

  摘要：

  一系列4-芳基-6,7,8,9-四氢苯并[4,5]噻吩并[3,2- e ] [1,2,4]三唑[4,3 - a ]嘧啶-5（ 4 ħ） -酮（1，图2）的制备和对代表肠道病毒包括柯萨奇病毒人类B1（B1考克斯），人柯萨奇病毒B3（考克斯B3）进行测试，人脊髓灰质炎病毒3（PV3），人鼻病毒14（HRV14），人鼻病毒21（HRV 21）和人鼻病毒71（HRV 71）。发现这些物质中四氢苯环上的C-8-叔丁基对它们的肠病毒活性至关重要。该组中的一员1e，对筛选出的一系列病毒显示出一位数的微摩尔活性（1.6–8.85μM），并且Cox B1（> 11.2），Cox B3（> 11.5）和PV3（> 51.2）的最高选择性指数（SI）值）。相比之下，1p是针对所选HRV（1.8-2.6μM）的最活跃的类似物，在测试的化合物组中显示出最高的选择性指数。1p的SI值对于HRV14为11.5，对于HRV21为8

  DOI：

  10.1016/j.bmcl.2017.05.030
• 作为产物：
  描述：

  氰乙酸乙酯 在 吗啉 、 sulfur 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 6.0h， 生成 (R,S)-ethyl 2-(isothiocyanato)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
  参考文献：
  名称：

  C-8-叔丁基取代的4-芳基-6,7,8,9-四氢苯并[4,5]噻吩并[3,2- e ] [1,2,4]三唑[4,3]的肠病毒抑制活性-一个]嘧啶-5-（4 ħ） -酮

  摘要：

  一系列4-芳基-6,7,8,9-四氢苯并[4,5]噻吩并[3,2- e ] [1,2,4]三唑[4,3 - a ]嘧啶-5（ 4 ħ） -酮（1，图2）的制备和对代表肠道病毒包括柯萨奇病毒人类B1（B1考克斯），人柯萨奇病毒B3（考克斯B3）进行测试，人脊髓灰质炎病毒3（PV3），人鼻病毒14（HRV14），人鼻病毒21（HRV 21）和人鼻病毒71（HRV 71）。发现这些物质中四氢苯环上的C-8-叔丁基对它们的肠病毒活性至关重要。该组中的一员1e，对筛选出的一系列病毒显示出一位数的微摩尔活性（1.6–8.85μM），并且Cox B1（> 11.2），Cox B3（> 11.5）和PV3（> 51.2）的最高选择性指数（SI）值）。相比之下，1p是针对所选HRV（1.8-2.6μM）的最活跃的类似物，在测试的化合物组中显示出最高的选择性指数。1p的SI值对于HRV14为11.5，对于HRV21为8

  DOI：

  10.1016/j.bmcl.2017.05.030

文献信息

• Discovery, structure-activity relationship study and biological evaluation of 2-thioureidothiophene-3-carboxylates as a novel class of C-X-C chemokine receptor 2 (CXCR2) antagonists
  作者：Ding Xue、Wenmin Chen、Nouri Neamati

  DOI：10.1016/j.ejmech.2020.112387

  日期：2020.10

  The C-X-C motif ligand 8 and C-X-C chemokine receptor 2 (CXCL8-CXCR2) axis is involved in pathogenesis of various diseases including inflammation and cancers. Various CXCR2 antagonists are under development for several diseases. Our previous high-throughput cell-based assay specific for CXCR2 has identified a pyrimidine-based compound CX797 acting on CXCR2 down-stream signaling. A lead optimization campaign through scaffold-hopping strategy led to a series of 2-thioureidothiophene-3-carboxylates (TUTP) as novel CXCR2 antagonists. Structure-activity relationship study of TUTPs led to the identification of compound 52 that significantly inhibited CXCR2-mediated beta-arrestin recruitment signaling (IC50 = 1.1 +/- 0.01 mu M) with negligible effect on CXCL8-mediated cAMP signaling and calcium flux. Similar to the known CXCR2 antagonist SB265610, compound 52 inhibited CXCL8-CXCR2 induced phosphorylation of ERK1/2. TUTP compounds also inhibited CXCL8-mediated cell migration and showed synergy with doxorubicin in ovarian cancer cells, thereby supporting TUTPs as promising compounds for cancer treatment. (C) 2020 Elsevier Masson SAS. All rights reserved.
• 2-(Diethylamino)thieno[1,3]oxazin-4-ones as Stable Inhibitors of Human Leukocyte Elastase
  作者：Michael Gütschow、Lars Kuerschner、Ulf Neumann、Markus Pietsch、Reik Löser、Norman Koglin、Kurt Eger

  DOI：10.1021/jm991108w

  日期：1999.12.1

  A series of 2-(diethylamino)thieno[1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno[2,3-d][1,3]oxazin-4-ones bearing various substituents at positions 5 and 6. Both thieno[2,3-d] and thieno[3,2-d] fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one, exhibited a K-i value of 5.8 nM. 2-(Diethylamino)thieno[1,3]oxazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophene replacement accounts for an enhanced stability of the acyl-enzyme intermediates.
• Enterovirus inhibitory activity of C-8- tert -butyl substituted 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2- e ][1,2,4]triazolo[4,3- a ]pyrimidin-5(4 H )-ones
  作者：Bishyajit Kumar Biswas、Yashwardhan R. Malpani、Neul Ha、Do-Hyun Kwon、Jin Soo Shin、Hae-Soo Kim、Chonsaeng Kim、Soo Bong Han、Chong-Kyo Lee、Young-Sik Jung

  DOI：10.1016/j.bmcl.2017.05.030

  日期：2017.8

  Members of a series of 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-ones (1, Fig. 2) were prepared and tested against representative enteroviruses including Human Coxsackievirus B1 (Cox B1), Human Coxsackievirus B3 (Cox B3), human Poliovirus 3 (PV3), human Rhinovirus 14 (HRV14), human Rhinovirus 21 (HRV 21) and human Rhinovirus 71 (HRV 71). The C-8-tert-butyl

  一系列4-芳基-6,7,8,9-四氢苯并[4,5]噻吩并[3,2- e ] [1,2,4]三唑[4,3 - a ]嘧啶-5（ 4 ħ） -酮（1，图2）的制备和对代表肠道病毒包括柯萨奇病毒人类B1（B1考克斯），人柯萨奇病毒B3（考克斯B3）进行测试，人脊髓灰质炎病毒3（PV3），人鼻病毒14（HRV14），人鼻病毒21（HRV 21）和人鼻病毒71（HRV 71）。发现这些物质中四氢苯环上的C-8-叔丁基对它们的肠病毒活性至关重要。该组中的一员1e，对筛选出的一系列病毒显示出一位数的微摩尔活性（1.6–8.85μM），并且Cox B1（> 11.2），Cox B3（> 11.5）和PV3（> 51.2）的最高选择性指数（SI）值）。相比之下，1p是针对所选HRV（1.8-2.6μM）的最活跃的类似物，在测试的化合物组中显示出最高的选择性指数。1p的SI值对于HRV14为11.5，对于HRV21为8