39478-63-2Relevant academic research and scientific papers
Structure-Functional-Selectivity Relationship Studies of Novel Apomorphine Analogs to Develop D1R/D2R Biased Ligands
Liu, Chuan,Park, Hyejin,Urs, Aarti N.,Urs, Nikhil M.,Wang, Qiu,Zimmerman, Joseph
, (2020/02/06)
Loss of dopamine neurons is central to the manifestation of Parkinson's disease motor symptoms. The dopamine precursor L-DOPA, the most commonly used therapeutic agent for Parkinson's disease, can restore normal movement yet cause side-effects such as dyskinesias upon prolonged administration. Dopamine D1 and D2 receptors activate G-protein- A nd arrestin-dependent signaling pathways that regulate various dopamine-dependent functions including locomotion. Studies have shown that shifting the balance of dopamine receptor signaling toward the arrestin pathway can be beneficial for inducing normal movement, while reducing dyskinesias. However, simultaneous activation of both D1 and D2Rs is required for robust locomotor activity. Thus, it is desirable to develop ligands targeting both D1 and D2Rs and their functional selectivity. Here, we report structure-functional-selectivity relationship (SFSR) studies of novel apomorphine analogs to identify structural motifs responsible for biased activity at both D1 and D2Rs.
Convenient synthesis of (S)-(+)-apomorphine from (R)-(-)-apomorphine
Davis,Seyhan,Soine,Smith
, p. 1056 - 1058 (2007/10/02)
A method was devised for preparing (S)-(+)-apomorphine from (R)-(-)-apomorphine. Dehydrogenation of the dimethyl ether of (R)-(-)-apomorphine with 10% palladium-on-carbon carbon followed by reduction with sodium cyanoborohydride under acidic conditions resulted in quantitative racemization to given (R,S)-apomorphine dimethyl ether, which then was resolved with (-)-tartaric acid. Ether cleavage of (S)-(+)-apomorphine dimethyl ether (-)-tartrate with hydriodic acid in acetic anhydride yielded (S)-(+)-apomorphine, which was isolated as the hydrochloride salt in 99% enantiomeric excess.
