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

Abstract

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 x L(-1), respectively.

CONCLUSION:

NO donating-SD derivatives are worthy to be futher investigated.

• Authors: Zhi-guo Zhang, Yi-hua Zhang, Hui Ji, Su-gan Qiu, Xiao-chun Feng
• Journal: Yao xue xue bao = Acta pharmaceutica Sinica (Yao Xue Xue Bao) Vol. 39 Issue 9 Pg. 705-10 (Sep 2004) ISSN: 0513-4870 [Print] China
• PMID: 15606018 (Publication Type: Journal Article)

Chemical References

• Anti-Asthmatic Agents
• Benzoquinones
• Guanidines
• Heptanoic Acids
• Hydroxylamines
• Nitric Oxide Donors
• Oxadiazoles
• furoxans
• Nitric Oxide
• seratrodast
• Histamine
• hydroxyguanidine
• Acetylcholine

Topics

• Acetylcholine
• Animals
• Anti-Asthmatic Agents (chemical synthesis, pharmacology, therapeutic use)
• Asthma (chemically induced, prevention & control)
• Benzoquinones (chemical synthesis, pharmacology, therapeutic use)
• Guanidines (chemistry, pharmacology)
• Guinea Pigs
• Heptanoic Acids (chemical synthesis, pharmacology, therapeutic use)
• Histamine
• Hydroxylamines
• Nitric Oxide (metabolism)
• Nitric Oxide Donors (chemistry, pharmacology)
• Oxadiazoles (chemistry, pharmacology)
• Structure-Activity Relationship