Structure-Functional Selectivity Relationship Studies on A-86929 Analogs and Small Aryl Fragments toward the Discovery of Biased Dopamine D1 Receptor Agonists was written by Li, Haoxi;Mirabel, Rosa;Zimmerman, Joseph;Ghiviriga, Ion;Phidd, Darian K.;Horenstein, Nicole;Urs, Nikhil M.. And the article was included in ACS Chemical Neuroscience in 2022.Recommanded Product: 3929-47-3 This article mentions the following:
Dopamine regulates normal functions such as movement, reinforcement learning, and cognition, and its dysfunction has been implicated in multiple psychiatric and neurol. disorders. Dopamine acts through D1- (D1R and D5R) and D2-class (D2R, D3R, and D4R) receptors and activates both G protein- and 閻?arrestin-dependent signaling pathways. Current dopamine receptor-based therapies are used to ameliorate motor deficits in Parkinson’s disease or as antipsychotic medications for schizophrenia. These drugs show efficacy for ameliorating only some symptoms caused by dopamine dysfunction and are plagued by debilitating side effects. Studies in primates and rodents have shown that shifting the balance of dopamine receptor signaling toward the arrestin pathway can be beneficial for inducing normal movement, while reducing motor side effects such as dyskinesias, and can be efficacious at enhancing cognitive function compared to balanced agonists. Several structure-activity relationship (SAR) studies have embarked on discovering 閻?arrestin-biased dopamine agonists, focused on D2 partial agonists, noncatechol D1 agonists, and mixed D1/D2R dopamine receptor agonists. Here, we describe an SAR study to identify novel D1R 閻?arrestin-biased ligands using A-86929, a high-affinity D1R catechol agonist, as a core scaffold to identify chem. motifs responsible for 閻?arrestin-biased activity at both D1 and D2Rs. Most of the A-86929 analogs screened were G protein-biased, but none of them were exclusively arrestin-biased. Addnl., various small-fragment mol. probes displayed weak bias toward the 閻?arrestin pathway. Continued in-depth SFSR (structure-functional selectivity relationship) studies informed by structure determination, mol. modeling, and mutagenesis studies will facilitate the discovery of potent and efficacious arrestin-biased dopamine receptor ligands. In the experiment, the researchers used many compounds, for example, 3-(3,4-Dimethoxyphenyl)propan-1-ol (cas: 3929-47-3Recommanded Product: 3929-47-3).
3-(3,4-Dimethoxyphenyl)propan-1-ol (cas: 3929-47-3) belongs to ethers. Of all the functional groups, ethers are the least reactive ones. Ether bonds are quite stable towards bases, oxidizing agents and reducing agents. But on the other hand, ethers undergo cleavage by reaction with acids. Electron-deficient reagents are also stabilized by ethers. For example, borane (BH3) is a useful reagent for making alcohols. Pure borane exists as its dimer, diborane (B2H6), a toxic gas that is inconvenient and hazardous to use. Borane forms stable complexes with ethers, however, and it is often supplied and used as its liquid complex with tetrahydrofuran (THF).Recommanded Product: 3929-47-3
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem