Renal vasodilators. The role of the 4-substituent in isoquinolin-3-ol cardiovascular agents: 4-ureido derivatives of isoquinolin-3-ol with selective renal vasodilator properties.

The synthesis and cardiovascular evaluation of a series of isoquinolin-3-ol derivatives bearing a variety of nitrogen substituents (amino, acylamino, carbamate, and ureido) at C-4 are described. Certain of these compounds have a selective renal vasodilating profile and have minimal effects on arterial blood pressure or heart rate when administered intravenously in the instrumented anesthetized dog. The most potent renal vasodilator in the series is 4-(allylureido)-6,7-dimethoxyisoquinolin-3-ol (38), which at a dose of 1.2 mg/kg iv produces a 97% maximal increase in renal blood flow without significant hypotensive or chronotropic effects. Structure-activity observations on the nature of the 4-substituent and the alkoxy substitution pattern in the aromatic ring of the isoquinolinol nucleus are discussed.

Amidino benzimidazole inhibitors of bacterial two-component systems.

Amidino benzimidazoles have been identified as inhibitors of the bacterial KinA/Spo0F two-component system (TCS). Many of these inhibitors exhibit good in vitro antibacterial activity against a variety of susceptible and resistant Gram-positive organisms. The moiety at the 2-position of the benzimidazole was extensively modified. In addition, the regioisomeric benzoxazoles, heterocyclic replacements for the benzimidazole, have been synthesized and their activity against the TCS evaluated.