- Structure-activity relationships in a series of xanthine derivatives with antibronchoconstrictory and bronchodilatory activities
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Thirty-one 1,3,7,8-substituted xanthine derivatives have been synthesized and evaluated for bronchodilator and anti-bronchoconstrictory activities in in vitro tracheal relaxation and in vivo bronchospasm inhibition models. Activity tests have been complemented with phosphodiesterase inhibition and toxicological data. Structure-activity relationships are discussed. Compound 21 (1,3-diisobutyl-8-methylxanthine) has been selected for further pharmacological development because of its good activity profile and favourable therapeutic index, which is 14- and 38-fold greater than that of theophylline and IBMX, respectively.
- Merlos,Gomez,Vericat,Bartroli,Garcia-Rafanell,Forn
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p. 653 - 658
(2007/10/02)
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- New xanthine derivatives with potent and long lasting anti-bronchoconstrictive activity
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Twenty eight new derivatives of 8-aminoalkyl substituted xanthine have been synthesized.They all have demonstrated a potent anti-bronchoconstrictive effect in the guinea pig and some of them have a very long duration of action (>48 h).Among them, one compound: 1-methyl 3-isobutyl 8-(4-benzhydryl piperazino ethyl)xanthine (57) (S 9795) has been selected for clinical trials in asthmatic patients because of its long duration of action, its lack of CNS stimulating effects and its inhibiting action on mast cell degranulation and phosphodiesterase activity.Keywords - 8-aminoalkyl substituted xanthines / benzhydryl piperazine / piperidine / ethylenediamine / anti-bronchoconstrictors / phosphodiesterase inhibitors / asthma
- Regnier, Gilbert L.,Guillonneau, Claude G.,Duhault, Jacques L.,Tisserand, Francoise P.,Saint-Romas, Guy,Holstorp, Sophie M.
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p. 243 - 250
(2007/10/02)
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