Ulrich Niewohner

Imidazo[5,1-f][1,2,4]triazin-4(3H)-ones, a new class of potent PDE 5 inhibitors

2-aryl-substituted imidazo[5,1-f][1,2,4]triazin-4(3H)-ones represent a new class of potent cGMP-PDE 5 inhibitors that prove to be superior to other purine-isosteric inhibitors. Subnanomolar inhibitors of PDE 5 with activity in in vivo models for erectile dysfunction have been identified. BAY 38-9456 (Vardenafil-hydrochloride) has been selected for clinical studies in the indication of erectile dysfunction.

Phosphodiesterase type 5 (PDE5) inhibitors.

Publisher Summary In recent years, the field of Phosphodiesterase Type 5 (PDE5) inhibitors has reached a state of maturity. Standard issues in medicinal chemistry, such as potency, selectivity, physico-chemical properties and oral bioavailability, have been successfully addressed with the known PDE5 inhibitors. The discovery of further PDE subtypes and the need for specific drug tissue distribution patterns result in a further increase in the knowledge of this PDE inhibitor class. In addition, knowledge gained in different kinase inhibitor classes is fruitful for PDE inhibitors and vice versa. As a plethora of PDEs are already known and new subtypes are still being discovered, scientists in the PDE5 inhibitor field are constantly challenged to continue the search for either more selective inhibitors, compounds with a specifically desirable combination of different PDE inhibitory properties, or compounds demonstrating a very specific tissue distribution.

A novel approach to amidines from esters

Abstract A mild and efficient method for the direct conversion of aromatic, benzylic and aliphatic esters to amidines—in the form of their hydrochlorides—has been developed.