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 published the artcile< Design, Synthesis, and Structure-Activity Relationships of Novel 2-Substituted Pyrazinoylguanidine Epithelial Sodium Channel Blockers: Drugs for Cystic Fibrosis and Chronic Bronchitis>, Application In Synthesis of 52244-70-9, the main research area is pyrazinoylguanidine epithelial sodium channel blocker preparation.
Amiloride, 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 analogs 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 I [R = NH(CH2)4C6H4O(CH2)2OH-4, NH(CH2)4C6H4O(CH2)3OH-4, NH(CH2)4C6H4OCH2CH(OH)CH2OH-4 (both R and S isomers)] showed the greatest potency on ENaC with IC50 values below 10 nM. A regioselective difference in potency was found, whereas no stereospecific difference in potency on ENaC was displayed. Lead compound I [R = NH(CH2)4C6H4OCH2CH(OH)CH2OH-4 (racemic)] was 102-fold more potent and 5-fold less reversible than amiloride and displayed the lowest IC50 value ever reported for an ENaC blocker.
Journal of Medicinal Chemistry published new progress about Chronic bronchitis. 52244-70-9 belongs to class ethers-buliding-blocks, and the molecular formula is C11H16O2, Application In Synthesis of 52244-70-9.
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem