Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372499 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
Abstract
In a continuing effort to discover novel PDE5 inhibitors, we have successfully found quinazolines with 4-benzylamino substitution as potent and selective PDE5 inhibitors. Initial lead compound (1) was found to be easily metabolized when incubated with human liver microsomes mainly through C6 amide hydrolysis. Blocking of this metabolic hot spot led to discovery of 10 (CKD533) which is highly potent, selective and orally efficacious in conscious rabbit model for erectile dysfunction and now is undergoing preclinical toxicology study.
Graphical abstractProperty-based design of potent and selective PDE5 inhibitor is described.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
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Organic Chemistry
Authors
Hojin Choi, Jaekwang Lee, Young Hoon Kim, Dai Sig Im, In-Chang Hwang, Soo Jin Kim, Seung Kee Moon, Hong Woo Lee, Sung Sook Lee, Soon Kil Ahn, Sang Woong Kim, Nam Song Choi, Kyung Joo Lee,