Synthesis, Molecular Modeling, and Biological Evaluation of Novel Tetrahydro-?-Carboline Hydantoin and Tetrahydro-?-Carboline Thiohydantoin Derivatives as Phosphodiesterase 5 Inhibitors.

ABSTRACT: Two series of fused tetrahydro-?-carboline hydantoin and tetrahydro-?-carboline thiohydantoin derivatives with a pendant 2,4-dimethoxyphenyl at position 5 were synthesized, and chiral carbons at positions 5 and 11a swing from R,R to R,S, S,R, and S,S. The prepared analogues were evaluated for their capacity to inhibit phosphodiesterase 5 (PDE5) isozyme. The R absolute configuration of C-5 in the ?-carboline hydantoin derivatives was found to be essential for the PDE5 inhibition. Chiral carbon derived from amino acid even if of the S configuration (L-tryptophan) may lead to equiactive or more active isomers than those derived from amino acid with the R configuration (D-tryptophan). This expands the horizon from which efficient PDE5 inhibitors can be derived and may offer an economic advantage. The thiohydantoin derivatives were less active than their hydantoin congeners.

SUBMITTER: Abadi AH 

PROVIDER: S-EPMC4939265 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature