Synthesis, Molecular Modeling, and Biological Evaluation of Novel Tetrahydro-β-Carboline Hydantoin and Tetrahydro-β-Carboline Thiohydantoin Derivatives as Phosphodiesterase 5 Inhibitors. (12th January 2011)

• Record Type: Journal Article
• Authors: Abadi, Ashraf H.; Lehmann, Jochen; Piazza, Gary A.; Abdel-Halim, Mohammad; Ali, Mohamed S. M.
• Other Names: You Qidong Academic Editor.
• Is Part Of: International journal of medicinal chemistry. Volume 2011(2011)
• Publication Date: 2011-01-12
• Subjects: Pharmaceutical chemistry -- Periodicals; Chemistry, Pharmaceutical; Pharmaceutical chemistry; Periodicals; 615.19
• DOI: 10.1155/2011/562421
• Languages: English
• ISSNs: 2090-2069

Abstract

Abstract : Two series of fused tetrahydro- β -carboline hydantoin and tetrahydro- β -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 β -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.