Metabolic stability optimization and metabolite identification of 2,5-thiophene amide 17β-hydroxysteroid dehydrogenase type 2 inhibitors.

2.50
Hdl Handle:
http://hdl.handle.net/10033/346134
Title:
Metabolic stability optimization and metabolite identification of 2,5-thiophene amide 17β-hydroxysteroid dehydrogenase type 2 inhibitors.
Authors:
Gargano, Emanuele M; Perspicace, Enrico; Hanke, Nina; Carotti, Angelo; Marchais-Oberwinkler, Sandrine; Hartmann, Rolf W
Abstract:
17β-HSD2 is a promising new target for the treatment of osteoporosis. In this paper, a rational strategy to overcome the metabolic liability in the 2,5-thiophene amide class of 17β-HSD2 inhibitors is described, and the biological activity of the new inhibitors. Applying different strategies, as lowering the cLogP or modifying the structures of the molecules, compounds 27, 31 and 35 with strongly improved metabolic stability were obtained. For understanding biotransformation in the 2,5-thiophene amide class the main metabolic pathways of three properly selected compounds were elucidated.
Affiliation:
Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, D-66123 Saarbrücken, Germany.
Citation:
Metabolic stability optimization and metabolite identification of 2,5-thiophene amide 17β-hydroxysteroid dehydrogenase type 2 inhibitors. 2014, 87:203-19 Eur J Med Chem
Journal:
European journal of medicinal chemistry
Issue Date:
24-Nov-2014
URI:
http://hdl.handle.net/10033/346134
DOI:
10.1016/j.ejmech.2014.09.061
PubMed ID:
25259513
Type:
Article
Language:
en
ISSN:
1768-3254
Appears in Collections:
publications of the department drug design and optimization (HIPS]DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorGargano, Emanuele Men
dc.contributor.authorPerspicace, Enricoen
dc.contributor.authorHanke, Ninaen
dc.contributor.authorCarotti, Angeloen
dc.contributor.authorMarchais-Oberwinkler, Sandrineen
dc.contributor.authorHartmann, Rolf Wen
dc.date.accessioned2015-03-04T10:43:11Zen
dc.date.available2015-03-04T10:43:11Zen
dc.date.issued2014-11-24en
dc.identifier.citationMetabolic stability optimization and metabolite identification of 2,5-thiophene amide 17β-hydroxysteroid dehydrogenase type 2 inhibitors. 2014, 87:203-19 Eur J Med Chemen
dc.identifier.issn1768-3254en
dc.identifier.pmid25259513en
dc.identifier.doi10.1016/j.ejmech.2014.09.061en
dc.identifier.urihttp://hdl.handle.net/10033/346134en
dc.description.abstract17β-HSD2 is a promising new target for the treatment of osteoporosis. In this paper, a rational strategy to overcome the metabolic liability in the 2,5-thiophene amide class of 17β-HSD2 inhibitors is described, and the biological activity of the new inhibitors. Applying different strategies, as lowering the cLogP or modifying the structures of the molecules, compounds 27, 31 and 35 with strongly improved metabolic stability were obtained. For understanding biotransformation in the 2,5-thiophene amide class the main metabolic pathways of three properly selected compounds were elucidated.en
dc.language.isoenen
dc.titleMetabolic stability optimization and metabolite identification of 2,5-thiophene amide 17β-hydroxysteroid dehydrogenase type 2 inhibitors.en
dc.typeArticleen
dc.contributor.departmentPharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, D-66123 Saarbrücken, Germany.en
dc.identifier.journalEuropean journal of medicinal chemistryen

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