173206-13-8Relevant articles and documents
COMPOUNDS AND METHODS FOR CD73 MODULATION AND INDICATIONS THEREFOR
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Paragraph 0239, (2021/06/11)
Disclosed are compounds of Formula I: or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein R1, R2, R3, A, L, and G are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.
Designing Functionally Selective Noncatechol Dopamine D1 Receptor Agonists with Potent in Vivo Antiparkinsonian Activity
Martini, Michael L.,Ray, Caroline,Yu, Xufen,Liu, Jing,Pogorelov, Vladimir M.,Wetsel, William C.,Huang, Xi-Ping,McCorvy, John D.,Caron, Marc G.,Jin, Jian
, p. 4160 - 4182 (2019/09/12)
Dopamine receptors are important G protein-coupled receptors (GPCRs) with therapeutic opportunities for treating Parkinson's Disease (PD) motor and cognitive deficits. Biased D1 dopamine ligands that differentially activate G protein over β-arrestin recruitment pathways are valuable chemical tools for dissecting positive versus negative effects in drugs for PD. Here, we reveal an iterative approach toward modification of a D1-selective noncatechol scaffold critical for G protein-biased agonism. This approach provided enhanced understanding of the structural components critical for activity and signaling bias and led to the discovery of several novel compounds with useful pharmacological properties, including three highly GS-biased partial agonists. Administration of a potent, balanced, and brain-penetrant lead compound from this series results in robust antiparkinsonian effects in a rodent model of PD. This study suggests that the noncatechol ligands developed through this approach are valuable tools for probing D1 receptor signaling biology and biased agonism in models of neurologic disease.
One-Pot Highly Regioselective Synthesis of Indole-Fused Pyridazino[4,5- b ][1,4]benzoxazepin-4(3 H)-ones by a Smiles Rearrangement
Jiang, Xiaolei,Hu, Fangdong
supporting information, p. 1207 - 1210 (2018/03/23)
A simple and convenient synthesis of indole-fused pyridazino[4,5- b ][1,4]benzoxazepin-4(3 H)-ones is described. A range of 2-(1 H -indol-2-yl)phenols and 4,5-dichloropyridazin-3-ones are compatible with this reaction. A Smiles rearrangement is proposed as a key step in the highly regioselective construction of the products. The easy availability of the starting materials makes this an appealing method in organic synthesis.