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

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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

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

doi

10.1016/j.bmcl.2009.10.071

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

383-6

issue

1

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)01482-6

journal_volume

20

pub_type

杂志文章

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