Author/Authors :
Yingzhi Bi، نويسنده , , Patrick Stoy، نويسنده , , Leonard Adam، نويسنده , , Bin He، نويسنده , , John Krupinski، نويسنده , , Diane Normandin، نويسنده , , Ron Pongrac، نويسنده , , Laurie Seliger، نويسنده , , Andrew Watson، نويسنده , , John E. Macor، نويسنده ,
Abstract :
In a continuing effort to discover novel chemotypes as potent and selective PDE5 inhibitors for the treatment of male erectile dysfunction (ED), we have found that 4-benzylaminoquinoline derivatives are very potent and selective PDE5 inhibitors. Some compounds in this series had PDE5 IC50ʹs as low as 50 pM. While an electron withdrawing group at the C6-position of the quinoline substantially improved PDE5 potency, an ethyl group at the C8-position not only improved the PDE5 potency but also the isozyme selectivity. Substitutents at the C3-position can incorporate a variety of different groups. The synthesis and primary structure–activity relationship of this new series of potent PDE5 inhibitors are described.
