{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T07:54:59Z","timestamp":1776239699739,"version":"3.50.1"},"reference-count":9,"publisher":"Wiley","license":[{"start":{"date-parts":[[2011,2,23]],"date-time":"2011-02-23T00:00:00Z","timestamp":1298419200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"Faculty of Postgraduate Studies, German University in Cairo"},{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2011,2,23]]},"abstract":"Two series of fused tetrahydro-\u03b2<\/jats:italic>-carboline hydantoin and tetrahydro-\u03b2<\/jats:italic>-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<\/jats:italic> to R,S, S,R,<\/jats:italic> and S,S<\/jats:italic>. The prepared analogues were evaluated for their capacity to inhibit phosphodiesterase 5 (PDE5) isozyme. The R<\/jats:italic> absolute configuration of C-5 in the \u03b2<\/jats:italic>-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<\/jats:italic>-tryptophan) may lead to equiactive or more active isomers than those derived from amino acid with the R<\/jats:italic> configuration (D<\/jats:italic>-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.<\/jats:p>","DOI":"10.1155\/2011\/562421","type":"journal-article","created":{"date-parts":[[2011,2,23]],"date-time":"2011-02-23T19:50:36Z","timestamp":1298490636000},"page":"1-9","source":"Crossref","is-referenced-by-count":4,"title":["Synthesis, Molecular Modeling, and Biological Evaluation of Novel Tetrahydro-\u03b2<\/i>-Carboline Hydantoin and Tetrahydro-\u03b2<\/i>-Carboline Thiohydantoin Derivatives as Phosphodiesterase 5 Inhibitors"],"prefix":"10.1155","volume":"2011","author":[{"given":"Ashraf H.","family":"Abadi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Department of Pharmaceutical\/Medicinal Chemistry, Friedrich-Schiller University, Philosophenweg 14, 07743 Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary A.","family":"Piazza","sequence":"additional","affiliation":[{"name":"Division of Drug Discovery, Department of Biochemistry and Molecular Biology, Southern Research Institute, The University of Alabama at Birmingham, 2000 Ninth Avenue South, Birmingham, AL 35205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Abdel-Halim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed S. 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