1.
Arch Pharm (Weinheim)
; 344(3): 149-57, 2011 Mar.
Article
in English
| MEDLINE
| ID: mdl-21384413
ABSTRACT
Starting from tadalafil as a template, a series of functionalized tetrahydro-ß-carboline derivatives have been prepared and identified as novel potent and selective PDE5 inhibitors. Replacing the 3,4-methylenedioxyphenyl at position 6 of tadalafil, together with elongation of the N2-methyl substituent and manipulation of the stereochemical aspects of the two chiral carbons led to the identification of compound XXI, a highly potent PDE5 inhibitor (IC(50) = 3 nM). Compound XXI was also highly selective for PDE5 versus PDE3B, PDE4B, and PDE11A, with a selectivity index of 52 and 235 towards PDE5 rather than PDE11 with both cAMP and cGMP as substrate, respectively.