N-(3-carbamoylthiophen-2-yl)furan-2-carboxamide | 58979-92-3

• 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: N-(3-carbamoylthiophen-2-yl)furan-2-carboxamide
• 英文别名: 2-(furan-2-carbonylamino)-thiophene-3-carboxylic acid amide；furan-2-carboxylic acid 3-carbamoyl-thiophen-2-ylamide
• CAS: 58979-92-3
• 化学式: C₁₀H₈N₂O₃S
• mdl: MFCD04430391
• 分子量: 236.251
• InChiKey: HEIVIJJEKZUFAZ-UHFFFAOYSA-N

物化性质

• 熔点：
  220 °C(Solv: ethanol (64-17-5))
• 沸点：
  337.5±32.0 °C(Predicted)
• 密度：
  1.483±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(3-carbamoylthiophen-2-yl)furan-2-carboxamide 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 2-(2-Furyl)-4-oxo-3,4-dihydrothieno<2,3-d>pyrimidin
  参考文献：
  名称：

  Bourguignon,J. et al., Bulletin de la Societe Chimique de France, 1975, p. 2483 - 2487

  摘要：

  DOI：
• 作为产物：
  描述：

  呋喃甲酰氯 、 2-胺噻吩-3-羰基胺 在 吡啶 作用下， 反应 1.0h， 以82%的产率得到N-(3-carbamoylthiophen-2-yl)furan-2-carboxamide
  参考文献：
  名称：

  Anti-glioma effects of 2-aminothiophene-3-carboxamide derivatives, ANO1 channel blockers

  摘要：

  Anoctamin1 (ANO1), a calcium-activated chloride ion channel (CaCC), is associated with various physiological functions including cancer progression and metastasis/invasion. ANO1 has been considered as a promising target for cancer therapeutics as ANO1 is over-expressed in a variety of cancers including glioblastoma (GBM) and inhibition of ANO1 has been reported to suppress cell proliferation, migration and invasion in GBM. GBM is one of the most common and aggressive cancers with poor prognosis with median survival for 15 months. Lack of effective treatment options against GBM emphasizes urgent necessity of effective GBM therapeutics. In an effort to discover potent and selective ANO1 inhibitors capable of inhibiting GBM cells, we have designed and synthesized a series of new 2-aminothiophene-3-carboxamide derivatives and performed SAR studies using both fluorescent cellular membrane potential assay and whole-cell patch-clamp recording. We observed that among these substances, 9c and 10q strongly suppress ANO1 channel activities and possess remarkable selectivity over ANO2. Unique structural feature of 10q, a cyclopentane-fused thiophene-3-carboxamide derivative, is the presence of benzoylthiourea functionality which dramatically contributes to activity. Both 9c and 10q suppress more strongly proliferation of GBM cells than four reference compounds including 3, Ani-9 and are also capable of inhibiting much more strongly colony formation than reference compounds in both 2D colony formation assay and 3D soft agar assay using U251 glioma cells. In addition, 9c and 10q suppress far more strongly migration/invasion of GBM cells than reference compounds. We, for the first time, found that the combination of ANO1 inhibitor (9c or 3) and temozolomide (TMZ) brings about remarkable synergistic effects in suppressing proliferation of GBM cells. Our study may provide an insight into designing selective and potent ANO1 inhibitors aiming at GBM treatment.

  DOI：

  10.1016/j.ejmech.2020.112688

文献信息

• BOURGUIGNON J.; MOREAU M.; QUEGUINER G.; PASTOUR P., BULL. SOC. CHIM. FRANCE <BSCF-AS>, 1975, NO 11-12, PART. 2, 2483-2487
  作者：BOURGUIGNON J.、 MOREAU M.、 QUEGUINER G.、 PASTOUR P.

  DOI：——

  日期：——
• Bourguignon,J. et al., Bulletin de la Societe Chimique de France, 1975, p. 2483 - 2487
  作者：Bourguignon,J. et al.

  DOI：——

  日期：——
• Anti-glioma effects of 2-aminothiophene-3-carboxamide derivatives, ANO1 channel blockers
  作者：Seung-Hye Choi、SeongShick Ryu、Kyoungmi Sim、Chiman Song、Injae Shin、Seong-Seop Kim、Young-Sun Lee、Jae-Yong Park、Taebo Sim

  DOI：10.1016/j.ejmech.2020.112688

  日期：2020.12

  Anoctamin1 (ANO1), a calcium-activated chloride ion channel (CaCC), is associated with various physiological functions including cancer progression and metastasis/invasion. ANO1 has been considered as a promising target for cancer therapeutics as ANO1 is over-expressed in a variety of cancers including glioblastoma (GBM) and inhibition of ANO1 has been reported to suppress cell proliferation, migration and invasion in GBM. GBM is one of the most common and aggressive cancers with poor prognosis with median survival for 15 months. Lack of effective treatment options against GBM emphasizes urgent necessity of effective GBM therapeutics. In an effort to discover potent and selective ANO1 inhibitors capable of inhibiting GBM cells, we have designed and synthesized a series of new 2-aminothiophene-3-carboxamide derivatives and performed SAR studies using both fluorescent cellular membrane potential assay and whole-cell patch-clamp recording. We observed that among these substances, 9c and 10q strongly suppress ANO1 channel activities and possess remarkable selectivity over ANO2. Unique structural feature of 10q, a cyclopentane-fused thiophene-3-carboxamide derivative, is the presence of benzoylthiourea functionality which dramatically contributes to activity. Both 9c and 10q suppress more strongly proliferation of GBM cells than four reference compounds including 3, Ani-9 and are also capable of inhibiting much more strongly colony formation than reference compounds in both 2D colony formation assay and 3D soft agar assay using U251 glioma cells. In addition, 9c and 10q suppress far more strongly migration/invasion of GBM cells than reference compounds. We, for the first time, found that the combination of ANO1 inhibitor (9c or 3) and temozolomide (TMZ) brings about remarkable synergistic effects in suppressing proliferation of GBM cells. Our study may provide an insight into designing selective and potent ANO1 inhibitors aiming at GBM treatment.