48198-89-6

Upstream product

• 41777-53-1 2,2-Dimethyl-propionic acid 4-(2-benzyloxycarbonylamino-ethyl)-2-(2,2-dimethyl-propionyloxy)-phenyl ester 
• 51-61-6 dopamine 
• 67302-25-4 N-t-Butoxycarbonyl-O,O-dipivaloyldopamin 
• 37034-31-4 N-(tert-butoxycarbonyl)dopamine 
• 62-31-7 dopamine hydrochloride 
• 37034-22-3 N-benzyloxycarbonyl-3,4-dihydroxyphenylethylamine 

Downstream Products

• 51-61-6 dopamine 

Relevant academic research and scientific papers

Brain-specific delivery of dopamine mediated by N, N-dimethyl amino group for the treatment of Parkinson's disease

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.

Brain-specific analogues of centrally acting amines

The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are compounds of the formula STR1 and the non-toxic pharmaceutically acceptable salts thereof, wherein D is the residue of a centrally acting primary, secondary or tertiary amine and STR2 is an unsubstituted or substituted dihydropyridyl, dihydroquinolyl or dihydroisoquinolyl radical. The corresponding ionic pyridinium, quinolinium and isoquinolinium salts STR3 X-, wherein X- is the anion of a non-toxic pharmaceutically acceptable acid, are also disclosed.

Synthesis and chemical properties of ibopamine and of related esters of N-substituted dopamines - Synthesis of ibopamine metabolites

The therapeutic usefulness of intravenously infused dopamine in congestive heart failure and in shock prompted us to synthesize a wide series of 3,4-O-diesters of dopamine and N-substituted derivatives to obtain an orally active dopamine-like prodrug having adequate absorption and duration of action. The pharmacological results and in particular, the hemodynamic studies in the dog led to the selection of ibopamine, i.e. the 3,4-diisobutyryl ester of N-methyldopamine and to its development as a useful drug for the chronic treatment of congestive heart failure. The choice of ibopamine from among several analogs was also influenced by other favourable properties such as good chemical stability in pharmaceutical formulations and in the biopharmaceutical phases of the absorption, and fast enzymatic activation of the prodrug by plasma and peripheral tissue esterases; the latter property appeared desirable to avoid any accumulation in the central nervous system and consequent undesired side effects. The isomeric mixture of 3-O- and 4-O- isobutyrates of N-methyldopamine as well as the main conjugated metabolites, i.e. the 3-O- and 4-O-sulphate and 4-O-β-glucuronide of N-methyldopamine were synthesized as analytical references in metabolic studies and for the investigation of their pharmacokinetic and pharmacological properties. Dopamine O-sulphates were also prepared using the methods developed for the corresponding N-methyl derivatives.

tert-Butoxycarbanyl as a convenient protecting group in synthesis of potential centrally active dopamine derivatives.

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.