67302-25-4Relevant academic research and scientific papers
Brain-specific delivery of dopamine mediated by N, N-dimethyl amino group for the treatment of Parkinson's disease
Li, Yanping,Zhou, Yangyang,Qi, Bowen,Gong, Tao,Sun, Xun,Fu, Yao,Zhang, Zhirong
, p. 3174 - 3185 (2014)
Parkinson's disease (PD) has become one of the most deadly diseases due to a lack of effective treatment. Herein, N-3,4-bis(pivaloyloxy)dopamine-3- (dimethylamino)propanamide (PDDP), a brain-specific derivative of dopamine, was designed and synthesized, which consists of a brain targeted ligand, N,N-dimethyl amino group, and two dipivaloyloxy groups for lipophilic modification. PDDP was investigated both in vitro and in vivo by comparing with L-DOPA and another derivative (BPD) without N,N-dimethyl amino group. PDDP showed a more pronounced accumulation in mouse brain microvascular endothelial cells (bEnd.3) than BPD via an active transport process. The increased cellular uptake of PDDP was proven to be mediated by putative pyrilamine cationic transporters. Following intravenous administration, the concentration of PDDP in the brain was 269.28-fold and 6.41-fold higher than that of L-DOPA and BPD at 5 min, respectively. Additionally, PDDP effectively attenuated the striatum lesion caused by 6-hydroxydopamine (6-OHDA) in rats. More importantly, PDDP presented antioxidant and antiapoptotic effects on 6-OHDA-induced toxicity in human neuroblastoma cells (SH-SY5Y). Thus, N,N-dimethyl amino group-based PDDP represents an effective and safe treatment for PD.
tert-Butoxycarbanyl as a convenient protecting group in synthesis of potential centrally active dopamine derivatives.
Walker,Ayres,Block,Lock
, p. 558 - 559 (2007/10/06)
Several pivaloyl and pivaloyloxy esters and amides of dopamine were synthesized for possible antiparkinson activity. The compounds were synthesized by select O- and N-acylation and N-methylation procedures. The tert-butoxycarbonyl function is an effective and easily removed nitrogen-protecting group for dopamine. Preliminary biological testing results showed that all compounds tested elicited a hypothermic response in mice, while only O,O-dipivaloyl-N,N-dimethyldopamine reversed reserpine-induced motor depression in mice. However, it is difficult to conclude from the preliminary data that the observed biological effects were due to central dopaminergic receptor stimulation.
