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Design, synthesis and antiasthmatic activities of NO-donating seratrodast derivatives

Zhang, Z-guo.; Zhang, Y-hua.; Ji, H.; Qiu, S-gan.; Feng, X-chun.

Yao Xue Xue Bao 39(9): 705-710

2004

ISSN/ISBN: 0513-4870
PMID: 15606018
Document Number: 578462
Aim To search for novel antiasthmatic agents. Methods Coupling seratrodast (SD), an antiasthmatic drug, with several different types of NO donors including oxatriazoles, N-hydroxyguanidines and furoxans; evaluating the antiasthmatic effects of coupled compounds by determining their inhibitory activity of guinea pig asthma induced by acetylcholine and histamine; and assessing NO releasing ability. Results Nine novel target compounds (I1-9) were synthesized, and their structures were established by IR, NMR, MS and elemental analysis. Preliminary pharmacological test showed that most of the compounds showed high antiasthmatic activities ( the latent period of induced asthma was prolonged from 10 s (SD) to 26 - 62 s), among which 3 compounds (I4, I6, I7,) were more potent than SD (P 0.05, P 0.01) and released more NO than others. The maximum concentrations (Cmax) of NO-release in vitro were 0.1878, 0.1393 and 0.2473 mg . L-1, respectively. Conclusion NO donating-SD derivatives are worthy to be futher investigated.

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