Thyroid receptor ligands. Part 8: Thyromimetics derived from N-acylated-alpha-amino acid derivatives displaying modulated pharmacological selectivity compared with KB-141
| Autor: | Johnny Sandberg, Karin Mellström, Mahmoud Rahimi-Ghadim, Denis E. Ryono, Gary J. Grover, Zhang Minsheng, Peter Agback, Neeraj Garg, William N. Washburn, Marlena Grynfarb, Ana Maria Garcia Collazo, Yolanda Caringal, Wei Meng, Robert Paul Brigance, Yi-Lin Li, Stefan Rehnmark, Chris Litten, Johan Malm, Thomas Anders Norin |
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| Rok vydání: | 2007 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science CHO Cells Ligands Biochemistry Cholesterol Dietary Radioligand Assay Cricetulus In vivo Cricetinae Drug Discovery Radioligand Animals Amino Acids Molecular Biology Phenylacetates chemistry.chemical_classification Thyroid hormone receptor Receptors Thyroid Hormone Ligand binding assay Phenyl Ethers Organic Chemistry Molecular Mimicry Biological activity In vitro Amino acid Rats chemistry Molecular Medicine Selectivity |
| Zdroj: | Bioorganicmedicinal chemistry letters. 17(15) |
| ISSN: | 0960-894X |
| Popis: | Based on the scaffold of the pharmacologically selective thyromimetic 2b, structurally a close analog to KB-141 (2a), a number of novel N-acylated-α-amino acid derivatives were synthesized and tested in a TR radioligand binding assay as well as in a reporter cell assay. On the basis of TRβ1-isoform selectivity and affinity, as well as affinity to the reporter cell assay, 3d was selected for further studies in the cholesterol-fed rat model. In this model 3d revealed an improved therapeutic window between cholesterol and TSH lowering but decreased margins versus tachycardia compared with 2a. |
| Databáze: | OpenAIRE |
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