81246-47-1Relevant academic research and scientific papers
Probing the Existence of a Metastable Binding Site at the β2-Adrenergic Receptor with Homobivalent Bitopic Ligands
Gaiser, Birgit I.,Danielsen, Mia,Marcher-R?rsted, Emil,R?pke J?rgensen, Kira,Wróbel, Tomasz M.,Frykman, Mikael,Johansson, Henrik,Br?uner-Osborne, Hans,Gloriam, David E.,Mathiesen, Jesper Mosolff,Sejer Pedersen, Daniel
, p. 7806 - 7839 (2019/09/07)
Herein, we report the development of bitopic ligands aimed at targeting the orthosteric binding site (OBS) and a metastable binding site (MBS) within the same receptor unit. Previous molecular dynamics studies on ligand binding to the β2-adrenergic receptor (β2AR) suggested that ligands pause at transient, less-conserved MBSs. We envisioned that MBSs can be regarded as allosteric binding sites and targeted by homobivalent bitopic ligands linking two identical pharmacophores. Such ligands were designed based on docking of the antagonist (S)-alprenolol into the OBS and an MBS and synthesized. Pharmacological characterization revealed ligands with similar potency and affinity, slightly increased β2/β1AR-selectivity, and/or substantially slower β2AR off-rates compared to (S)-alprenolol. Truncated bitopic ligands suggested the major contribution of the metastable pharmacophore to be a hydrophobic interaction with the β2AR, while the linkers alone decreased the potency of the orthosteric fragment. Altogether, the study underlines the potential of targeting MBSs for improving the pharmacological profiles of ligands.
Synthesis of 6,16,22,32-tetrahydroxy[3.3.3.3]metacyclophane with the aid of a new copper catalyst
Burns, Dennis H.,Miller, Jeffrey D.
, p. 5189 - 5192 (2007/10/02)
Metacyclophane 2 has been prepared in 4 steps starting from 2- bromoanisole with the aid of a new copper catalyst. The catalyst was prepared by mixing CuBr-SMe2 with LiSPh and LiBr in THF.
Methylase Models: Studies on General-Base vs. Nucleophilic Catalysis in the Intramolecular Alkylation of Phenols
Knipe, Jay O.,Vasquez, Peter J.,Coward, James K.
, p. 3202 - 3209 (2007/10/02)
The ortho substituted phenols, 1 and 3, have been synthesized as models for the O-methylation of catecholamines, as catalyzed by catechol O-methyltransferase.The decomposition of 1 and 3 was studied at 40 deg C over a wide range of pH in both oxyanion and
