摘要
目的设计合成2,3,3a,4-四氢硫色烯并[4,3-c]吡唑类化合物,并对其抗真菌活性进行初步评价。方法以取代苯硫酚为起始原料,首先合成中间体3-次苄基硫色满酮;然后利用水合肼和3-次苄基硫色满酮在醋酸中反应生成目标化合物。采用二倍稀释法对目标化合物的体外抗真菌活性进行测试。结果共合成了8个新的2,3,3a,4-四氢硫色烯并[4,3-c]吡唑类化合物,并经过H-核磁共振、质谱和元素分析等确认了其结构。抗真菌活性实验结果表明,目标化合物对大部分供试真菌具有好的活性。结论2,3,3a,4-四氢硫色烯并[4,3-c]吡唑类化合物在体外具有抗真菌活性,有待深入研究。
Abstract
OBJECTIVE To design and synthesize 2,3,3a,4-tetrahydrothiochromeno[4,3-c]pyrazole derivatives and measure their antifungal activity in vitro.METHODS The intermediate of 3-benzylidene-1-thiochromanones was synthesized from the substituted benzenethiols.secondly,the target compounds were obtained by the reactions of hydrazine with 3-benzylidene-1-thiochromanones in acetic acid.The antifungal activity of the target compounds in vitro was measured by consecutive double dilution.RESULTS Eight new 2,3,3a,4-tetrahydrothiochromeno[4,3-c]pyrazole derivatives were synthesized,and then their structures were identified by 1H-NMR,MS and elemental analysis.The result of antifungal activity indicated that the target compounds had good antifungal effects on most tested fungi.CONCLUSION 2,3,3a,4-tetrahydrothiochromeno-[4,3-c]pyrazole derivatives show antifungal activity in vitro,which required further research in the future.
关键词
硫色满酮 /
3-次苄基硫色满酮 /
微波辐射 /
抗真菌活性
{{custom_keyword}} /
Key words
thiochromanones /
3-arylidene-1-thiochromanones /
microwave irradiation /
anti-fungus activeness
{{custom_keyword}} /
马正月;闫国英;杨更亮;祝士国;管立.
2,3,3a,4-四氢硫色烯并[4,3-c]吡唑类化合物合成及其体外抗真菌活性研究[J]. 中国药学杂志, 2009, 44(08): 630-633
M Zheng-yue;YN Guo-ying;YNG Geng-ling;ZHU Shi-guo;GUN Li.
Synthesis and Antifungal Activities in Vitro of 2,3,3a,4-Tetrahydrothiochromeno[4,3-c]pyrazole Derivatives [J]. Chinese Pharmaceutical Journal, 2009, 44(08): 630-633
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] ZHANG H，BAI D L. Research development of antifungal medicines[J]. Chin J Med Chem(中国药物化学杂志)，1997，7(4)：303-310.
[2] NAKIB T A，BEZJAK V，MEGAN M J，et al. Synthesis and antifungal activity of some 3-benzylidenethiochroman-4-ones[J]. Eur J Med Chem，1990，25(5)：455-462.
[3] LIU Y，LUO W，SUN L，et al. Synthesis and antifungal activity of 3-substituted thiochromanones [J]. Drug Discov Ther，2008，2(4)：216-218.
[4] TRAMONTINI M，ANGIOLINI L. Further advances in the chemistry of Mannich bases[J]. Tetrahedron，1990，46(6):1791-1837.
[5] QI P，JIN Y H，GUO C，et al. Syntheses and the antifungal activity of 3-bromo-4-thio- chrom(an)ones[J]. Chin J Med Chem(中国药物化学杂志)，2003，13(4)：205-207.
[6] QI P，JIN Y H，GUO C，et al. Synthesis of 3-benzylidenethiochroman-4-ones and their in vitro antifungal activity[J]. Chin J New Drugs(中国新药杂志)，2004，13(2)：141-143.
[7] QI P，JIN Y H，GUO C，et al. Synthesis and antifungal activities of the Mannich bases of thiochromanones[J]. Chin J Med Chem(中国药物化学杂志)，2003，13(4)：134-137.
[8] ZHU Q H，FANG L，ZHANG G L. Synthesis and antifungal activities of the mannich baes of thiochromanones derivatives[J]. Chin J Med Chem(中国药物化学杂志)，2000，10(1)：1-3.
[9] LIU T L，XIE J H，YU S L. Synthesis of bioactive dihyudropyrazole derivatives [J]. Acta Sci Nat Univ Nankai[南开大学学报(自然科学)]，1999，32(1)：101-104.
[10] CUI P，LIU X H，ZHI L P，et al. Synthesis and biological activity of novel 5-aryl-N-pyrazole oxime ester derivative[J]. Chin J Appl Chem（应用化学），2008，25(7)：820-824.
[11] LIU X H. Synthesis and antibacterial activity of novel aryl pyrazole derivatives[J]. Chin J Synth Chem，2007，15(2)：212-215.
[12] LI J Z，JIANG L，AN Y M.Synthesis，characterization and bioactivity of furoyl pyrazol- one- β-alanine complexs[J]. Chin J Appl Chem（应用化学），2004，21(2)：150-153.
[13] ALBERT L，KATALIN E K，JóZSEF J. Synthesis of tricyclic fused pyrazolines by the reaction of 3-arylidenechromanones and 3-arylidene-1-thiochromanones with hydrazine[J]. ARKIVOC，2007，Part (viii):26-39.
[14] XIAO L W，LI H Z. Synthesis of β-arylthioethers of propionic acid and thioch- romanones under microwave irradiation[J]. Chin J Org Chem(有机化学)，2006，26(5)：979-982.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
河北科技攻关项目资金资助(07276407D和06276479B)
{{custom_fund}}
