2,5-bis[2-isopropoxy-4-(2-pyridylimino)aminophenyl]thiophene | 1322586-52-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2,5-bis[2-isopropoxy-4-(2-pyridylimino)aminophenyl]thiophene
• 英文别名: DB1867；N-[3-propan-2-yloxy-4-[5-[2-propan-2-yloxy-4-(pyridine-2-carboximidoylamino)phenyl]thiophen-2-yl]phenyl]pyridine-2-carboximidamide
• CAS: 1322586-52-6
• 化学式: C₃₄H₃₄N₆O₂S
• 分子量: 590.749
• InChiKey: MSBONHYBUVHKOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  甲烷磺酸 、 2,5-bis[2-isopropoxy-4-(2-pyridylimino)aminophenyl]thiophene 以 乙醇 为溶剂， 生成 2,5-bis[2-isopropoxy-4-(2-pyridylimino)aminophenyl]thiophene dimesylate
  参考文献：
  名称：

  Phenotypic evaluation and in silico ADMET properties of novel arylimidamides in acute mouse models of <em>Trypanosoma cruzi</em> infection

  摘要：

  Arylimidamides (AIAs), previously termed as reversed amidines, present a broad spectrum of activity against intracellular microorganisms. In the present study, three novel AIAs were evaluated in a mouse model of Trypanosoma cruzi infection, which is the causative agent of Chagas disease. The bis-AIAs DB1957, DB1959 and DB1890 were chosen based on a previous screening of their scaffolds that revealed a very promising trypanocidal effect at nanomolar range against both the bloodstream trypomastigotes (BTs) and the intracellular forms of the parasite. This study focused on both mesylate salts DB1957 and DB1959 besides the hydrochloride salt DB1890. Our current data validate the high activity of these bis-AIA scaffolds that exhibited EC50 (drug concentration that reduces 50% of the number of the treated parasites) values ranging from 14 to 78 nM and 190 to 1,090 nM against bloodstream and intracellular forms, respectively, also presenting reasonable selectivity indexes and no mutagenicity profile predicted by in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET). Acute toxicity studies using murine models revealed that these AIAs presented only mild toxic effects such as reversible abdominal contractions and ruffled fur. Efficacy assays performed with Swiss mice infected with the Y strain revealed that the administration of DB1957 for 5 \consecutive days, with the first dose given at parasitemia onset, reduced the number of BTs at the peak, ranging between 21 and 31% of decrease. DB1957 was able to provide 100% of animal survival, while untreated animals showed 70% of mortality rates. DB1959 and DB1890B did not reduce circulating parasitism but yielded >80% of survival rates.

  DOI：

  10.2147/dddt.s120618
• 作为产物：
  描述：

  1-bromo-2-isopropoxy-4-nitrobenzene 在 四(三苯基膦)钯 、 tin(II) chloride dihdyrate 作用下， 以 1,4-二氧六环 、 乙醇 、 二甲基亚砜 、 乙腈 为溶剂， 生成 2,5-bis[2-isopropoxy-4-(2-pyridylimino)aminophenyl]thiophene
  参考文献：
  名称：

  Phenotypic evaluation and in silico ADMET properties of novel arylimidamides in acute mouse models of <em>Trypanosoma cruzi</em> infection

  摘要：

  Arylimidamides (AIAs), previously termed as reversed amidines, present a broad spectrum of activity against intracellular microorganisms. In the present study, three novel AIAs were evaluated in a mouse model of Trypanosoma cruzi infection, which is the causative agent of Chagas disease. The bis-AIAs DB1957, DB1959 and DB1890 were chosen based on a previous screening of their scaffolds that revealed a very promising trypanocidal effect at nanomolar range against both the bloodstream trypomastigotes (BTs) and the intracellular forms of the parasite. This study focused on both mesylate salts DB1957 and DB1959 besides the hydrochloride salt DB1890. Our current data validate the high activity of these bis-AIA scaffolds that exhibited EC50 (drug concentration that reduces 50% of the number of the treated parasites) values ranging from 14 to 78 nM and 190 to 1,090 nM against bloodstream and intracellular forms, respectively, also presenting reasonable selectivity indexes and no mutagenicity profile predicted by in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET). Acute toxicity studies using murine models revealed that these AIAs presented only mild toxic effects such as reversible abdominal contractions and ruffled fur. Efficacy assays performed with Swiss mice infected with the Y strain revealed that the administration of DB1957 for 5 \consecutive days, with the first dose given at parasitemia onset, reduced the number of BTs at the peak, ranging between 21 and 31% of decrease. DB1957 was able to provide 100% of animal survival, while untreated animals showed 70% of mortality rates. DB1959 and DB1890B did not reduce circulating parasitism but yielded >80% of survival rates.

  DOI：

  10.2147/dddt.s120618

文献信息

• Phenotypic evaluation and in silico ADMET properties of novel arylimidamides in acute mouse models of &lt;em&gt;Trypanosoma cruzi&lt;/em&gt; infection
  作者：Cristiane França Da Silva、Denise da Gama Jaen Batista、Julianna Siciliano de Araújo、Edézio Ferreira Cunha-Junior、Chad E. Stephens、Moloy Banerjee、Abdelbasset A. Farahat、Senol Akay、Mary K. Fisher、David W. Boykin、Maria de Nazaré Correia Soeiro

  DOI：10.2147/dddt.s120618

  日期：——

  Arylimidamides (AIAs), previously termed as reversed amidines, present a broad spectrum of activity against intracellular microorganisms. In the present study, three novel AIAs were evaluated in a mouse model of Trypanosoma cruzi infection, which is the causative agent of Chagas disease. The bis-AIAs DB1957, DB1959 and DB1890 were chosen based on a previous screening of their scaffolds that revealed a very promising trypanocidal effect at nanomolar range against both the bloodstream trypomastigotes (BTs) and the intracellular forms of the parasite. This study focused on both mesylate salts DB1957 and DB1959 besides the hydrochloride salt DB1890. Our current data validate the high activity of these bis-AIA scaffolds that exhibited EC50 (drug concentration that reduces 50% of the number of the treated parasites) values ranging from 14 to 78 nM and 190 to 1,090 nM against bloodstream and intracellular forms, respectively, also presenting reasonable selectivity indexes and no mutagenicity profile predicted by in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET). Acute toxicity studies using murine models revealed that these AIAs presented only mild toxic effects such as reversible abdominal contractions and ruffled fur. Efficacy assays performed with Swiss mice infected with the Y strain revealed that the administration of DB1957 for 5 \consecutive days, with the first dose given at parasitemia onset, reduced the number of BTs at the peak, ranging between 21 and 31% of decrease. DB1957 was able to provide 100% of animal survival, while untreated animals showed 70% of mortality rates. DB1959 and DB1890B did not reduce circulating parasitism but yielded >80% of survival rates.