title: Chasing the Elusive Benzofuran Impurity of the THR Antagonist NH-3: Synthesis, Isotope Labeling, and Biological Activity.
abstract: We have synthesized and established the structure of a long-suspected, but hitherto unknown, benzofuran side product (EBI) formed during the synthesis of NH-3. Understanding the mechanism of its formation has enabled isotope (D) labeling. We further developed a highly efficient method for separating EBI from NH-3. Interestingly, EBI was found to be a very potent thyroid hormone receptor (THR) agonist, while NH-3 is an antagonist. In this process, we have also achieved a significantly improved synthesis of NH-3.
authors: Department of Pharmacology, University of California , Davis, California 95616, United States.
authors: Latika
authors: L
authors: Singh
authors: Department of Pharmacology, University of California , Davis, California 95616, United States.
authors: Brandon
authors: B
authors: Pressly
authors: Department of Neurobiology, Physiology, and Behavior, University of California Davis, California 95616, United States.
authors: Brenda J
authors: BJ
authors: Mengeling
authors: Department of Chemistry, University of California , Davis, California 95616, United States.
authors: James C
authors: JC
authors: Fettinger
authors: Department of Neurobiology, Physiology, and Behavior, University of California Davis, California 95616, United States.
authors: J David
authors: JD
authors: Furlow
authors: Department of Molecular Biosciences, School of Veterinary Medicine, University of California , Davis, California 95616, United States.
authors: Pamela J
authors: PJ
authors: Lein
authors: Department of Pharmacology, University of California , Davis, California 95616, United States.
authors: Heike
authors: H
authors: Wulff
authors: Department of Pharmacology, University of California , Davis, California 95616, United States.
authors: Vikrant
authors: V
authors: Singh
mesh_terms: D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001686:Biological Phenomena; D003500:Cyclization; D007553:Isotope Labeling; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009603:Nitroso Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011988:Receptors, Thyroid Hormone / Q000819:agonists* / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C000611323:2-(4-((7-Isopropyl-2-(4-nitrophenyl)benzofuran-5-yl)methyl)-3,5-dimethylphenoxy)acetic acid; C000611322:2-(4-(4-hydroxy-3-isopropyl-5-((4-nitrophenyl)ethynyl)benzyl)-3,5-dimethylphenoxy)acetic acid; D001572:Benzofurans; D001593:Benzyl Compounds; D009574:Nitro Compounds; D009603:Nitroso Compounds; D011988:Receptors, Thyroid Hormone