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Med Chem. 2018 Feb 21. doi: 10.2174/1573406414666180222093033. [Epub ahead of print]
Synthesis and biological evaluation of 12N-substituted tricyclic matrinic derivatives as a novel family of anti-influenza agents.
Tang S1, Li YH1, Cheng XY1, Yin JQ1, Li YH1, Song DQ1, Wang YX1, Liu ZD2.
Author information
Abstract
BACKGROUND:
Influenza is still a serious threat to human health with significant morbidity and mortality, so it is desirable to develop novel anti-flu drug agents with novel structures.
OBJECTIVE:
The main purpose of this research was to explore broad-spectrum anti-flu agents and provide antiviral stockpiles in response to potential future influenza pandemics.
METHODS:
Fifteen novel 12N-substituted tricyclic matrinic derivatives were synthesized and evaluated for their anti-influenza activities against H1N1 subtype taking 12N-p-cyanobenzenesulfonyl matrinane (1) as the lead. All prepared compounds were characterized by 1H NMR, 13C NMR and ESI-HRMS. The pharmacokinetics (PK) profile of the key compound was also examined in this study.
RESULT:
The structure-activity relationship study indicated that a suitable benzyl groups on 12N atom might be beneficial for the activity. Among them, 12N-p-carboxybenzyl matrinic butane (17g) exhibited the most promising activity with an IC50 value of 16.2 μM and a selective index (SI) value of over 33.4. In addition, compound 17g displayed a good in vivo pharmacokinetic profile with area under the curve (AUC0-∞) value of 9.89 μM?h.
CONCLUSION:
We consider tricyclic matrinic butane derivatives to be a new class of anti-influenza agents and this study provided useful information on further optimization.
Copyright? Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
KEYWORDS:
Drug-like; H1N1 subtype; Influenza A virus; Structure?activity relationship; Tricyclic matrinic derivatives; anti-virus.
PMID: 29473520 DOI: 10.2174/1573406414666180222093033
Synthesis and biological evaluation of 12N-substituted tricyclic matrinic derivatives as a novel family of anti-influenza agents.
Tang S1, Li YH1, Cheng XY1, Yin JQ1, Li YH1, Song DQ1, Wang YX1, Liu ZD2.
Author information
Abstract
BACKGROUND:
Influenza is still a serious threat to human health with significant morbidity and mortality, so it is desirable to develop novel anti-flu drug agents with novel structures.
OBJECTIVE:
The main purpose of this research was to explore broad-spectrum anti-flu agents and provide antiviral stockpiles in response to potential future influenza pandemics.
METHODS:
Fifteen novel 12N-substituted tricyclic matrinic derivatives were synthesized and evaluated for their anti-influenza activities against H1N1 subtype taking 12N-p-cyanobenzenesulfonyl matrinane (1) as the lead. All prepared compounds were characterized by 1H NMR, 13C NMR and ESI-HRMS. The pharmacokinetics (PK) profile of the key compound was also examined in this study.
RESULT:
The structure-activity relationship study indicated that a suitable benzyl groups on 12N atom might be beneficial for the activity. Among them, 12N-p-carboxybenzyl matrinic butane (17g) exhibited the most promising activity with an IC50 value of 16.2 μM and a selective index (SI) value of over 33.4. In addition, compound 17g displayed a good in vivo pharmacokinetic profile with area under the curve (AUC0-∞) value of 9.89 μM?h.
CONCLUSION:
We consider tricyclic matrinic butane derivatives to be a new class of anti-influenza agents and this study provided useful information on further optimization.
Copyright? Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
KEYWORDS:
Drug-like; H1N1 subtype; Influenza A virus; Structure?activity relationship; Tricyclic matrinic derivatives; anti-virus.
PMID: 29473520 DOI: 10.2174/1573406414666180222093033