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ID: ALA1153113

Journal: Bioorg Med Chem Lett

Title: Discovery of potent, selective, and orally bioavailable PDE5 inhibitor: Methyl-4-(3-chloro-4-methoxybenzylamino)-8-(2-hydroxyethyl)-7-methoxyquinazolin-6-ylmethylcarbamate (CKD 533).

Authors: Choi H, Lee J, Kim YH, Im DS, Hwang IC, Kim SJ, Moon SK, Lee HW, Lee SS, Ahn SK, Kim SW, Choi NS, Lee KJ.

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.

CiteXplore: 19906530

DOI: 10.1016/j.bmcl.2009.10.071