| Parallel solid-phase synthesis of disubstituted (5-biphenyltetrazolyl) hydantoins and thiohydantoins targeting the growth hormone secretagogue receptor. | |
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MedLine Citation:
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PMID: 14698149 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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An efficient solid-phase protocol for the synthesis of substituted (5-biphenyltetrazolyl)-hydantoins and -thiohydantoins has been developed. Suzuki cross-coupling between resin-bound 2-(tetrazol-5-yl)-phenylborinane and 4-bromobenzaldehyde gave the corresponding tetrazolylbiphenyl aldehyde. Subsequent reductive amination using amino acid esters gave the pivotal resin bound amino acid esters which were transformed to hydantoins or thiohydantoins via two routes: (i) treatment with isocyanates or isothiocyanates or (ii) successive treatment with triphosgene and primary amines. Using molecular modeling, we were able to jump from L-692,429, a well known non-peptidyl growth hormone secretagogue (GHS), to biphenyltetrazolyl hydantoins, obtaining compounds with IC(50) values below 600 nM after two iterative cycles only. |
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Authors:
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Rune Severinsen; Jesper F Lau; Kent Bondensgaard; Birgit S Hansen; Mikael Begtrup; Michael Ankersen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 14 ISSN: 0960-894X ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2004 Jan |
Date Detail:
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Created Date: 2003-12-30 Completed Date: 2004-09-21 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 317-20 Citation Subset: IM |
Affiliation:
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Medicinal Chemistry, Novo Nordisk A/S, Novo-Nordisk Park 2760, Maaloev, Denmark. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Drug Delivery Systems
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methods* Human Growth Hormone / secretion* Humans Hydantoins / chemical synthesis, metabolism Models, Molecular Receptors, G-Protein-Coupled / metabolism* Receptors, Ghrelin Receptors, Somatotropin / metabolism Thiohydantoins / chemical synthesis*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Hydantoins; 0/Receptors, G-Protein-Coupled; 0/Receptors, Ghrelin; 0/Receptors, Somatotropin; 0/Thiohydantoins; 12629-01-5/Human Growth Hormone |
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