57606-03-8

Upstream product

• 1477-68-5 3-Methoxytyramine hydrochloride 
• 554-52-9 3-Methoxytyramine 
• 1451411-31-6 2-(3,4-dimethoxyphenyl)-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]acetamide 
• 93-40-3 (3,4-Dimethoxyphenyl)acetic acid 
• 6429-04-5 1,2,3,4-tetrahydro-1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline hydrochloride 
• 22231-63-6 7-benzyloxy-6-methoxy-1-veratryl-3,4-dihydro-isoquinoline; hydrochloride 
• 59444-68-7 (+/-)-7-benzyloxy-6-methoxy-1-(3,4-dimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline 

Downstream Products

• 18783-43-2 pacodine 
• 1451411-40-7 N-benzyl-2-{1-[(3,4-dimethoxyphenyl)methyl]-6-methoxy-7-(3-methylbutoxy)-1,2,3,4-tetrahydroisoquinolin-2-yl}acetamide 
• 1451411-42-9 N-benzyl-2-[7-(cyclohexylmethoxy)-1-[(3,4-dimethoxyphenyl)-methyl]-6-methoxy-1,2,3,4-tetrahydroisoquinolin-2-yl]acetamide 
• 1451411-44-1 N-benzyl-2-{1-[(3,4-dimethoxyphenyl)methyl]-7-[2-(dimethylamino)ethoxy]-6-methoxy-1,2,3,4-tetrahydroisoquinolin-2-yl}acetamide 
• 1451411-46-3 N-benzyl-2-{1-[(3,4-dimethoxyphenyl)methyl]-7-[4-(dimethylamino)butoxy]-6-methoxy-1,2,3,4-tetrahydroisoquinolin-2-yl}acetamide 
• 1451411-48-5 N-benzyl-2-{1-[(3,4-dimethoxyphenyl)methyl]-6-methoxy-7-[2-(piperidin-1-yl)ethoxy]-1,2,3,4-tetrahydroisoquinolin-2-yl}-acetamide 
• 361388-45-6 N-benzyl-2-[7-(benzyloxy)-1-[(3,4-dimethoxyphenyl)methyl]-6-methoxy-1,2,3,4-tetrahydroisoquinolin-2-yl]acetamide 
• 1451411-51-0 N-benzyl-2-{1-[(3,4-dimethoxyphenyl)methyl]-6-methoxy-7-(pyridin-2-ylmethoxy)-1,2,3,4-tetrahydroisoquinolin-2-yl}acetamide 
• 1451411-53-2 N-benzyl-2-{1-[(3,4-dimethoxyphenyl)methyl]-6-methoxy-7-(pyridin-3-ylmethoxy)-1,2,3,4-tetrahydroisoquinolin-2-yl}acetamide 
• 1451411-55-4 N-benzyl-2-{1-[(3,4-dimethoxyphenyl)methyl]-6-methoxy-7-(4-phenoxybutoxy)-1,2,3,4-tetrahydroisoquinolin-2-yl}acetamide 
• 1451411-57-6 2-[(benzylcarbamoyl)methyl]-1-[(3,4-dimethoxyphenyl)methyl]-6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-yl butanoate 
• 1451411-59-8 2-[(benzylcarbamoyl)methyl]-1-[(3,4-dimethoxyphenyl)methyl]-6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-yl methanesulfonate 
• 1451411-61-2 2-[(benzylcarbamoyl)methyl]-1-[(3,4-dimethoxyphenyl)methyl]-6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-yl trifluoromethanesulfonate 
• 1451411-63-4 N-benzyl-2-{1-[(3,4-dimethoxyphenyl)methyl]-6-methoxy-7-(2,2,2-trifluoroethoxy)-1,2,3,4-tetrahydroisoquinolin-2-yl}acetamide 

Relevant academic research and scientific papers

Toward the development of bivalent ligand probes of cannabinoid CB1 and Orexin OX1 receptor heterodimers

Cannabinoid CB1 and orexin OX1 receptors have been suggested to form heterodimers and oligomers. Aimed at studying these complexes, a series of bivalent CB1 and OX1 ligands combining SR141716 and ACT-078573 pharmacophores were designed, synthesized, and tested for activity against CB1 and OX1 individually and in cell lines that coexpress both receptors. Compound 20 showed a robust enhancement in potency at both receptors when coexpressed as compared to individually expressed, suggesting possible interaction with CB1-OX1 dimers. Bivalent ligands targeting CB1-OX1 receptor dimers could be potentially useful as a tool for further exploring the roles of such heterodimers in vitro and in vivo.

Substituted tetrahydroisoquinolines as selective antagonists for the orexin 1 receptor

Increasing evidence implicates the orexin 1 (OX1) receptor in reward processes, suggesting OX1 antagonism could be therapeutic in drug addiction. In a program to develop an OX1 selective antagonist, we designed and synthesized a series of substituted tetrahydroisoquinolines and determined their potency in OX1 and OX2 calcium mobilization assays. Structure-activity relationship (SAR) studies revealed limited steric tolerance and a preference for electron deficiency at the 7-position. Pyridylmethyl groups were shown to be optimal for activity at the acetamide position. Computational studies resulted in a pharmacophore model and confirmed the SAR results. Compound 72 significantly attenuated the development of place preference for cocaine in rats.

Structural analyses of metabolites of phenolic 1- benzyltetrahydroisoquinolines in plant cell cultures by LC/NMR, LC/MS, and LC/CD

The metabolism of the phenolic 1-benzyltetrahydroisoquinoline alkaloids was studied in cell cultures of Macleaya and Corydalis species. The crude alkaloid fraction obtained from feeding experiments was investigated by application of the combined LC/NMR and LC/APCI-MS (/MS) techniques. Several metabolites were detected, and their structures (6 and 8-14) were identified. Bioconversion of the phenolic 1-benzyltetrahydroisoquinoline (2) into the pseudoprotoberberine (8) was demonstrated for the first time. LC/APCI-MS and LC/CD experiments carried out on a chiral column permitted the deduction of the major enantiomeric form of the chiral metabolites. Thus, the combination of NMR, MS, and CD data permitted the structural elucidation and stereochemical analysis of the metabolites in the extract matrix solution, without isolation and sample purification prior to the coupling experiments.