1609577-26-5

Upstream product

• 1609581-01-2 4-[3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]furo[3,2-c]pyridine 
• 1609577-24-3 4-[4-(3-chloro-5-methylpyridazin-4-yl)-3-methylphenoxy]furo[3,2-c]pyridine 
• 75-24-1 trimethylaluminum 
• 1609581-17-0 4-[4-(furo[3,2-c]pyridin-4-yloxy)-2-methylphenyl]-5-methyl-2-(tetrahydro-2H-pyran-2-yl)pyridazin-3(2H)-one 
• 1609259-67-7 4-chloro-5-methyl-2-(tetrahydro-2H-pyran-2-yl)pyridazin-3(2H)-one 
• 1609581-00-1 4-(4-bromo-3-methylphenoxy)furo[3,2-c]pyridine 
• 14472-14-1 4-bromo-3-methylphenol 
• 31270-80-1 4-chlorofuro[3,2-c]pyridine 

Downstream Products

• 1609579-68-1 4-[4-(3,5-dimethyl-2-oxidopyridazin-4-yl)-3-methylphenoxy]furo[3,2-c]pyridine 
• 1609581-91-0 4-[4-(3,5-dimethyl-1-oxidopyridazin-4-yl)-3-methylphenoxy]furo[3,2-c]pyridine 

Relevant academic research and scientific papers

Defining Structure-Functional Selectivity Relationships (SFSR) for a Class of Non-Catechol Dopamine D1 Receptor Agonists

G protein-coupled receptors (GPCRs) are capable of downstream signaling through distinct noncanonical pathways such as β-arrestins in addition to the canonical G protein-dependent pathways. GPCR ligands that differentially activate the downstream signaling pathways are termed functionally selective or biased ligands. A class of novel non-catechol G protein-biased agonists of the dopamine D1 receptor (D1R) was recently disclosed. We conducted the first comprehensive structure-functional selectivity relationship study measuring GS and β-arrestin2 recruitment activities focused on four regions of this scaffold, resulting in over 50 analogs with diverse functional selectivity profiles. Some compounds became potent full agonists of β-arrestin2 recruitment, while others displayed enhanced GS bias compared to the starting compound. Pharmacokinetic testing of an analog with an altered functional selectivity profile demonstrated excellent blood-brain barrier penetration. This study provides novel tools for studying ligand bias at D1R and paves the way for developing the next generation of biased D1R ligands.

HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS

The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof and N-oxides thereof; processes and intermediates for preparation of; and compositions and uses thereof. The present invention further provides D1 agonists with reduced D1R desensitization, D1 agonists with a reduced β- arrestin recruitment activity relative to Dopamine, D1 agonists interacting significantly with the Ser188 but not significantly with the Ser202 of a D1R when binding to the D1R, D1 agonists interacting less strongly with the Asp103 and interacting less strongly with the Ser198 of a D1R when binding to the D1R, and their uses.