35386-24-4Relevant articles and documents
Kinetics of the decomposition of a Mannich base.
Mollica,Smith,Nunes,Govan
, p. 1770 - 1774 (1970)
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Mild deprotection of the: N-tert -butyloxycarbonyl (N -Boc) group using oxalyl chloride
Awuah, Samuel G.,George, Nathaniel,Ofori, Samuel,Parkin, Sean
, p. 24017 - 24026 (2020/07/23)
We report a mild method for the selective deprotection of the N-Boc group from a structurally diverse set of compounds, encompassing aliphatic, aromatic, and heterocyclic substrates by using oxalyl chloride in methanol. The reactions take place under room temperature conditions for 1-4 h with yields up to 90percent. This mild procedure was applied to a hybrid, medicinally active compound FC1, which is a novel dual inhibitor of IDO1 and DNA Pol gamma. A broader mechanism involving the electrophilic character of oxalyl chloride is postulated for this deprotection strategy. This journal is
Leveraging a Low-Affinity Diazaspiro Orthosteric Fragment to Reduce Dopamine D3 Receptor (D3R) Ligand Promiscuity across Highly Conserved Aminergic G-Protein-Coupled Receptors (GPCRs)
Reilly, Sean W.,Riad, Aladdin A.,Hsieh, Chia-Ju,Sahlholm, Kristoffer,Jacome, Daniel A.,Griffin, Suzy,Taylor, Michelle,Weng, Chi-Chang,Xu, Kuiying,Kirschner, Nathan,Luedtke, Robert R.,Parry, Christopher,Malhotra, Shipra,Karanicolas, John,Mach, Robert H.
, p. 5132 - 5147 (2019/05/28)
Previously, we reported a 3-(2-methoxyphenyl)-9-(3-((4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)thio)propyl)-3,9-diazaspiro[5.5]undecane (1) compound with excellent dopamine D3 receptor (D3R) affinity (D3R Ki = 12.0 nM) and selectivity (D2R/D3R ratio = 905). Herein, we present derivatives of 1 with comparable D3R affinity (32, D3R Ki = 3.2 nM, D2R/D3R ratio = 60) and selectivity (30, D3R Ki = 21.0 nM, D2R/D3R ratio = 934). Fragmentation of 1 revealed orthosteric fragment 5a to express an unusually low D3R affinity (Ki = 2.7 μM). Compared to piperazine congener 31, which retains a high-affinity orthosteric fragment (5d, D3R Ki = 23.9 nM), 1 was found to be more selective for the D3R among D1- and D2-like receptors and exhibited negligible off-target interactions at serotoninergic and adrenergic G-protein-coupled receptors (GPCRs), common off-target sites for piperazine-containing D3R scaffolds. This study provides a unique rationale for implementing weakly potent orthosteric fragments into D3R ligand systems to minimize drug promiscuity at other aminergic GPCR sites.