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ID: ALA1147639

Journal: Bioorg Med Chem Lett

Title: Quinolines as extremely potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction.

Authors: Bi Y, Stoy P, Adam L, He B, Krupinski J, Normandin D, Pongrac R, Seliger L, Watson A, Macor JE.

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 IC(50)'s 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.

CiteXplore: 15006407

DOI: 10.1016/j.bmcl.2003.12.090