141019-01-4Relevant academic research and scientific papers
Design, synthesis, and structure-activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: Drugs for cystic fibrosis and chronic bronchitis
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
, p. 4098 - 4115 (2007/10/03)
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 analogues of amiloride were synthesized and evaluated for potency and reversibility on bronchial ENaC. All compounds tested were more potent and less reversible at blocking sodium-dependent short-circuit current than amiloride. Compounds 30-34 showed the greatest potency on ENaC with IC50 values below 10 nM. A regioselective difference in potency was found (compounds 30, 39, and 40), whereas no stereospecific (compounds 33, 34) difference in potency on ENaC was displayed. Lead compound 32 was 102-fold more potent and 5-fold less reversible than amiloríde and displayed the lowest IC50 value ever reported for an ENaC blocker.
Novel 5-Desmethylene Analogues of 5,10-Dideaza-5,6,7,8-tetrahydrofolic Acid as Potential Anticancer Agents
Taylor, Edward C.,Gillespie, Paul,Patel, Mona
, p. 3218 - 3225 (2007/10/02)
The synthesis and biological activity of novel 5-desmethylene analogues of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), a potent antitumor agent presently undergoing clinical trials, are described.These compounds are representative of a new series
