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Updated: Aug 25, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Quinolines as extremely potent and selective PDE5 inhibitors as potential agents for treatment of erectile
Yingzhi Bi1, Patrick Stoy, Leonard Adam
1Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. ybi@lexpharma.com
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.
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