title: [Design, synthesis and antiasthmatic activities of NO-donating seratrodast derivatives].
abstract: 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.
authors.affiliation: Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhi-guo
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Yi-hua
authors.initials: YH
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.forename: Su-gan
authors.initials: SG
authors.lastname: Qiu
authors.forename: Xiao-chun
authors.initials: XC
authors.lastname: Feng
mesh_terms: 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
chemical_list: 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