Design, synthesis, and structure-activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: drugs for cystic fibrosis and …

…, BJ Sargent, BD Swenson, A Usyatinsky…

Index: Hirsh, Andrew J.; Molino, Bruce F.; Zhang, Jianzhong; Astakhova, Nadezhda; Geiss, William B.; Sargent, Bruce J.; Swenson, Brian D.; Usyatinsky, Alexander; Wyle, Michael J.; Boucher, Richard C.; Smith, Rick T.; Zamurs, Andra; Johnson, M. Ross Journal of Medicinal Chemistry, 2006 , vol. 49, # 14 p. 4098 - 4115

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Citation Number: 74

Abstract

Amiloride (1), the prototypical epithelial sodium channel (ENaC) blocker, has been administered with limited success as aerosol therapy for improving pulmonary function in patients with the genetic disorder cystic fibrosis. This study was conducted to synthesize and identify more potent, less reversible ENaC blockers, targeted for aerosol therapy and possessing minimal systemic renal activity. A series of novel 2-substituted acylguanidine ...