| 1585244-85-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• CAS: 1585244-85-4
• 化学式: C₂₁H₂₅N₃O₄S
• 分子量: 415.513
• InChiKey: NMQAHMHCOXOXPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  101.73
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 生成 6-((3,5-bis(trifluoromethyl)phenyl)carbamothioyl)-2-(4-methylbenzamido)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide
  参考文献：
  名称：

  Discovery of a Novel Dual-Target Inhibitor of ERK1 and ERK5 That Induces Regulated Cell Death to Overcome Compensatory Mechanism in Specific Tumor Types

  摘要：

  ERK1 and ERK5 are proposed to have pivotal roles in several types of cancer. Under some circumstance, ERK5 may provide a common bypass route, which rescues proliferation upon abrogation of ERK1 signaling. Thus, we accurately classified the tumor types from The Cancer Genome Atlas (TCGA) based on the expression levels of ERK1 and ERK5. We proposed a novel therapeutic strategy to overcome the above-mentioned compensatory mechanism in specific tumor types by co-targeting both ERK1 and ERK5. On the basis of the idea of overcoming ERK5 compensation mechanism, 22ac (ADTL-EI1712) as the first selective dual-target inhibitor of ERK1 and ERK5 was discovered to have potent antitumor effects in vitro and in vivo. Interestingly, this compound was found to induce regulated cell death accompanied by autophagy in MKN-74 cells. Taken together, our results warrant the potential of this dual-target inhibitor as a new candidate drug that conquers compensatory mechanism in certain tumor types.

  DOI：

  10.1021/acs.jmedchem.9b01896
• 作为产物：
  描述：

  N-叔丁氧羰基-4-哌啶酮 在 吗啉 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Discovery of a Novel Dual-Target Inhibitor of ERK1 and ERK5 That Induces Regulated Cell Death to Overcome Compensatory Mechanism in Specific Tumor Types

  摘要：

  ERK1 and ERK5 are proposed to have pivotal roles in several types of cancer. Under some circumstance, ERK5 may provide a common bypass route, which rescues proliferation upon abrogation of ERK1 signaling. Thus, we accurately classified the tumor types from The Cancer Genome Atlas (TCGA) based on the expression levels of ERK1 and ERK5. We proposed a novel therapeutic strategy to overcome the above-mentioned compensatory mechanism in specific tumor types by co-targeting both ERK1 and ERK5. On the basis of the idea of overcoming ERK5 compensation mechanism, 22ac (ADTL-EI1712) as the first selective dual-target inhibitor of ERK1 and ERK5 was discovered to have potent antitumor effects in vitro and in vivo. Interestingly, this compound was found to induce regulated cell death accompanied by autophagy in MKN-74 cells. Taken together, our results warrant the potential of this dual-target inhibitor as a new candidate drug that conquers compensatory mechanism in certain tumor types.

  DOI：

  10.1021/acs.jmedchem.9b01896

文献信息

• Development of antimycobacterial tetrahydrothieno[2,3-c]pyridine-3-carboxamides and hexahydrocycloocta[b]thiophene-3-carboxamides: Molecular modification from known antimycobacterial lead
  作者：Radhika Nallangi、Ganesh Samala、Jonnalagadda Padma Sridevi、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.ejmech.2014.02.028

  日期：2014.4

  Twenty derivatives of 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide and ten of 2-substituted 4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carboxamide were synthesized by molecular modification of a known antimycobacterial molecule. Compounds were evaluated in vitro against Mycobacterium tuberculosis (MTB), and cytotoxicity against RAW 264.7 cell line. Among the compounds, 2-(4-phenoxybenzamido)-4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carboxamide (12f) was found to be the most active compound against MTB with MIC of 3.70 mu M and was more potent than Ethambutol (MIC of 7.64 mu M), Ciprofloxacin (MIC of 9.41 mu M) and standard lead compound SID 92097880 (MIC of 9.15 mu M). Compound 12f also showed MTB MIC of 1.23 mu M in the presence of an efflux pump inhibitor verapamil, and showed no cytotoxicity at 50 mu M. (C) 2014 Elsevier Masson SAS. All rights reserved.