Improvement of therapeutic index of phosphodiesterase type IV inhibitors as anti-Asthmatics.
Bioorg Med Chem Lett
; 13(14): 2355-8, 2003 Jul 21.
Article
in En
| MEDLINE
| ID: mdl-12824033
ABSTRACT
A new series of catechol hydrazines was synthesized and their structure-activity relationship (SAR) was analyzed for developing an effective phosphodiesterase 4 (PDE4) inhibitor as an anti-asthmatic drug candidate. Among the (E)-Analogues tested using in vitro assays, 5CC showed a strong PDE4 inhibitory activity and a significantly improved rolipram binding profile compared with rolipram, a prototype PDE4 inhibitor. Moreover, from in-vivo asthma model, we observed that (E)-Analogue 5CC had a good efficacy against guinea-pig respiratory tract inflammation and bronchoconstriction, along with a remarkably reduced emetic side effect, compared with rolipram. Conclusively, (E)-Analogue 5CC seems to be a promising candidate for the development of anti-asthmatic PDE4 inhibitors.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphodiesterase Inhibitors
/
3',5'-Cyclic-AMP Phosphodiesterases
/
Anti-Asthmatic Agents
Limits:
Animals
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2003
Document type:
Article