Design, Synthesis and Structure–Activity Relationship of Functionalized Tetrahydro‐β‐carboline Derivatives as Novel PDE5 Inhibitors
作者： Nermin S. Ahmed , Bernard D. Gary , Hethar N. Tinsley , Gary A. Piazza , Stefan Laufer
关键词:
摘要: Starting from tadalafil as a template, series of functionalized tetrahydro-b-carboline derivatives have been prepared and identified novel potent selective PDE5 inhibitors. Replacing the 3,4-methylenedioxyphenyl at position 6 tadalafil, together with elongation N2-methyl substituent manipulation stereochemical aspects two chiral carbons led to identification compound XXI, highly inhibitor (IC50 = 3 nM). Compound XXI was also for versus PDE3B, PDE4B, PDE11A, selectivity index 52 235 towards rather than PDE11 both cAMP cGMP substrate, respectively.
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