Synthesis, Molecular Modeling, and Biological Evaluation of Novel Tetrahydro-β-Carboline Hydantoin and Tetrahydro-β-Carboline Thiohydantoin Derivatives as Phosphodiesterase 5 Inhibitors
| Autor: | Jochen Lehmann, Mohamed S. M. Ali, Gary A. Piazza, Ashraf H. Abadi, Mohammad Abdel-Halim |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
chemistry.chemical_classification
Article Subject Molecular model Stereochemistry lcsh:RM1-950 Absolute configuration Hydantoin Biochemistry Isozyme Amino acid chemistry.chemical_compound lcsh:Therapeutics. Pharmacology chemistry Asymmetric carbon cGMP-specific phosphodiesterase type 5 Drug Discovery Molecular Medicine Research Article Biological evaluation |
| Zdroj: | International Journal of Medicinal Chemistry, Vol 2011 (2011) International Journal of Medicinal Chemistry |
| ISSN: | 2090-2077 2090-2069 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|