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


CONCLUSIONS
NO donating-SD derivatives are worthy to be futher investigated.
Zhang
Zhi-guo
ZG
Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
Zhang
Yi-hua
YH
Ji
Hui
H
Qiu
Su-gan
SG
Feng
Xiao-chun
XC
D000109:Acetylcholine; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000139:chemically induced / Q000517:prevention & control*; D016227:Benzoquinones / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D006538:Heptanoic Acids / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006632:Histamine; D006898:Hydroxylamines; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D018927:Anti-Asthmatic Agents; D016227:Benzoquinones; D006146:Guanidines; D006538:Heptanoic Acids; D006898:Hydroxylamines; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; C010166:furoxans; D009569:Nitric Oxide; C060230:seratrodast; D006632:Histamine; C029604:hydroxyguanidine; D000109:Acetylcholine