38291-33-7

Upstream product

• 186581-53-3 diazomethane 
• 314-19-2 apomorphine hydrochloride 
• 58-00-4 apomorphin 
• 65185-58-2 2-(2-bromophenyl)ethanamine 
• 74315-08-5 N-acetyl-2-(2-bromophenyl)ethylamine 
• 2033-89-8 3,4-dimethoxyphenol 
• 18605-42-0 10,11-dimethoxy-6-methyl-aporphane 
• 76-57-3 codeine 
• 641-36-1 Apocodeine 
• 74-88-4 methyl iodide 
• 39478-63-2 10,11-dimethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline 
• 18605-43-1 10,11-dimethoxy-6-methyl-5,6-dihydro-4H-dibenzo[de,g]quinoline 

Downstream Products

• 119597-07-8 N-[2-(5,6-dimethoxy-[1]phenanthryl)-ethyl]-N-methyl-benzamide 
• 18605-43-1 10,11-dimethoxy-6-methyl-5,6-dihydro-4H-dibenzo[de,g]quinoline 
• 58-00-4 apomorphin 
• 41035-30-7 (S)-(+)-apomorphine hydrochloride 
• 61013-20-5 10,11-dimethoxy-6-methyl-6H-dibenzo[de,g]quinoline 

Relevant academic research and scientific papers

Regio- and stereoselective derivatisation of an aporphine scaffold

Treatment of 10,11-dimethoxyaporphine with chromium hexacarbonyl was found to give two diastereoisomeric products on regioselective co-ordination of the chromium tricarbonyl fragment to the A ring. For one of the diastereoisomeric complexes, alkylation was found to proceed with high regio- and diastereoselectivity at C(4), whereas regio- and diastereoselective alkylation was observed at C(6a) for the other diastereoisomer. In the case of the C(4)- and C(6a)-methylated products, these substrates were decomplexed in high yield to give the corresponding enantiopure, C(4)- and C(6a)-methyl substituted aporphines.

PHARMACEUTICAL COMPOSITIONS OF (6AS)-6-METHYL-5,6,6A,7-TETRAHYDRO-4H-DIBENZO[DE,G]QUINOLINE-10,11-DIOL

This invention relates to pharmaceutical compositions for enhancing the solubility of (6aS)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol and salt forms thereof.

PHARMACEUTICAL COMPOSITION FOR USE IN THE TREATMENT OF NEUROLOGICAL DISEASES

The present invention relates to pharmaceutical compositions for administration to mammals that include (6aS)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient that provides pharmacokinetic profiles useful for the treatment of neurodegenerative diseases.

Structure-Functional-Selectivity Relationship Studies of Novel Apomorphine Analogs to Develop D1R/D2R Biased Ligands

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.

Racemization of (S)-(+)-10,11-dimethoxyaporphine and (S)-(+)-aporphine: efficient preparations of (R)-(-)-apomorphine and (R)-(-)-aporphine via a recycle process of resolution

Efficient preparations of (R)-(-)-apomorphine (R)-1 and (R)-(-)-aporphine (R)-2 based on a recycle process of resolution are described. In this recycle process of resolution, (RS)-(±)-10,11-dimethoxyaporphine 3 as the precursor of 1, and (RS)-(±)-aporphine 2 were successfully resolved into both enantiomers with (+)-dibenzoyltartaric acid (DBTA). The desired (R)-3 and (R)-2 were obtained and then, respectively, transformed to compound (R)-1, the hydrochloride salt of (R)-1, diacetate compound 4 and the hydrochloride salt of (R)-2; while the undesired (S)-3 and (S)-2 were racemized to obtain a racemate, which was suitable for further resolution. A method for the racemization of the undesired (S)-3 and (S)-2 was extensively studied, in order to obtain high-yielding racemization conditions. A plausible mechanism for the racemization of (S)-3 and (S)-2 was also proposed.

Convenient synthesis of (S)-(+)-apomorphine from (R)-(-)-apomorphine

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.