Design, synthesis and antiasthmatic activities of NO-donating seratrodast derivatives.
- Author:
Zhi-guo ZHANG
1
;
Yi-hua ZHANG
;
Hui JI
;
Su-gan QIU
;
Xiao-chun FENG
Author Information
- Publication Type:Journal Article
- MeSH: 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; Nitric Oxide; metabolism; Nitric Oxide Donors; chemistry; pharmacology; Oxadiazoles; chemistry; pharmacology; Structure-Activity Relationship
- From: Acta Pharmaceutica Sinica 2004;39(9):705-710
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo search for novel antiasthmatic agents.
METHODSCoupling 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.
RESULTSNine 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.
CONCLUSIONNO donating-SD derivatives are worthy to be futher investigated.
