Thyroid receptor ligands. Part 4: 4'-amido bioisosteric ligands selective for the thyroid hormone receptor beta

Autor:	Bolette Husman, Yi-Lin Li, Konrad F. Koehler, Johan Malm, Ana Maria Garcia Collazo, Chris Litten, Mathias Färnegård, Neeraj Garg, Karin Mellström, Johnny Sandberg, Marlena Grynfarb
Rok vydání:	2005
Předmět:	Agonist Models Molecular Thyroid Hormones medicine.drug_class Stereochemistry Protein Conformation Clinical Biochemistry Molecular Conformation Pharmaceutical Science Crystallography X-Ray Ligands Biochemistry Thyroid hormone receptor beta chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Humans Molecular Biology Phenylacetates Thyroid hormone receptor Molecular Structure Chemistry Ligand Phenyl Ethers Organic Chemistry Biological activity Thyroid Hormone Receptors beta Amides Protein Structure Tertiary Drug Design Molecular Medicine Triiodothyronine Bioisostere Thyroid Hormone Receptors alpha
Zdroj:	Bioorganicmedicinal chemistry letters. 16(4)
ISSN:	0960-894X
Popis:	Based on the examination of the X-ray crystallographic structures of the LBD of TRalpha and TRbeta in complex with KB-141 (2), a number of novel 4'-hydroxy bioisosteric thyromimetics were prepared. Optimal affinity and beta-selectivity (33 times), was found with a medium-sized alkyl-substituted amido group; iso-butyl (12c). It can be concluded that bioisosteric replacements of the 4'-hydroxy position represent a new promising class of TRbeta-selective synthetic thyromimetics.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd07802526973094a8d1c6ea23ac9725 https://pubmed.ncbi.nlm.nih.gov/16303304 Zobrazit plný text záznamu Full Text from ScienceDirect