- Design and synthesis of xanthine analogues as potent and selective PDE5 inhibitors
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We have discovered potent and selective xanthine PDE5 inhibitors. Compound 25 (PDE5 IC50=0.6 nM, PDE6/PDE5=101) demonstrated similar functional efficacy and PK profile to Sildenafil (PDE5 IC50=3.5 nM, PDE6/PDE5=7).
- Wang, Yuguang,Chackalamannil, Samuel,Hu, Zhiyong,Boyle, Craig D.,Lankin, Claire M.,Xia, Yan,Xu, Ruo,Asberom, Theodros,Pissarnitski, Dmitri,Stamford, Andrew W.,Greenlee, William J.,Skell, Jeffrey,Kurowski, Stanley,Vemulapalli, Subbarao,Palamanda, Jairam,Chintala, Madhu,Wu, Ping,Myers, Joyce,Wang, Peng
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p. 3149 - 3152
(2007/10/03)
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- 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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