Pyrazine diuretics. VI. (Pyrazinecarboxamido)guanidines

Abstract

The syiitliesis of it aeries of (pyrazinecarI~o~iti~ii~~~)giiaiiidiiies by :t iiiiiii1)cr of i i i v i ttods is rtcssczritwtl. 'Pltc-<~ iiid d u r e s i s i i i r a t s :iiid t i r J g S wliilcs ,f these coln~,oulldi I,rodilc,cYl t tl(1 inecllrbos:Lrnitl(J)giiaiiiiliiie.;. compouiids, like their N-amidiiiopviazitiecarboramitle arinlogs, cniisc: di potassium excretioii is unaffected or repressed. Cyclizat ioii of :t 1111 aiialogous pyrazinyltriazoles which were yelierally lehi potelit than the 'l'lic most gcnerd iiietliod for tlic preparation of these compounds irivolved the iiiteraciiori of' a met hy1 1)yruxinecarboxyl:ite (11) with tlw :tppropri:tte amiiiogu:zrlidine (route A). Other inethocls of preparatiou \vwe devised as alternate routes in those (:a tlic niethyl ester gave poor iwults a i d for cvidciicr i t i structure assig~inierit~ to the products.

Synthesis and characterization of methylbromoamiloride, a potential biochemical probe of epithelial Na+ channels

“…This goal was accomplished by methylation of a nitrogen in the acylguanidine moiety with tritiated methyl iodide of high specific activity. This acylguanidine side chain seems to be the most permissive position of the amiloride molecule in that modifications can be made here that do not seriously influence drug potency (Cragoe et al, 1967;Shepard et al, 1969;Garcia-Romeu, 1970;Benos et al, 1976;Cuthbert & Fanelli, 1978). The methylated bromoamiloride molecule (CH3BrA) was purified by both thin layer and high performance liquid chromatography, This compound inhibited both short-circuit current (l~c) of isolated frog skin and 22Na influx into apical plasma membrane vesicles made from A6 cells with the same or lower apparent inhibitory dissociation constant (K~) as bromoamiloride.…”