81580-84-9

Upstream product

• 86-51-1 2,3-dimethyoxybenzaldehyde 
• 845519-27-9 2-(2,3-dimethoxyphenyl)-5-oxo-tetrahydrofuran-3-carboxylic acid 
• 51114-94-4 (2-carboxyethyl)triphenylphosphonium bromide 

Downstream Products

• 24039-89-2 5,6-dimethoxy-1-tetralone 
• 59515-92-3 5,6-dihydroxy-3,4-dihydronaphthalen-1(2H)-one 
• 64400-76-6 4-(2',3'-dimethoxyphenyl)-3-butanoic acid 

Relevant academic research and scientific papers

Mapping the catechol binding site in dopamine D1 receptors: Synthesis and evaluation of two parallel series of bicyclic dopamine analogues

A novel class of isochroman dopamine analogues, originally reported by Abbott Laboratories, have >100-fold selectivity for D1-like over D2-like receptors. We synthesized a parallel series of chroman compounds and showed that repositioning the oxygen atom in the heterocyclic ring decreases potency and confers D2-like receptor selectivity to these compounds. Insilico modeling supports the hypothesis that the altered pharmacology for the chroman series is due to potential intramolecular hydrogen bonding between the oxygen in the chroman ring and the meta-hydroxy group of the catechol moiety. This interaction realigns the catechol hydroxy groups and disrupts key interactions between these ligands and critical serine residues in TM5 of the D1-like receptors. This hypothesis was tested by the synthesis and pharmacological evaluation of a parallel series of carbocyclic compounds. Our results suggest that if the potential for intramolecular hydrogen bonding is removed, D1-like receptor potency and selectivity are restored. What a difference an H bond makes: Structurally related chromans, isochromans, and their carbocyclic analogues were assessed for dopamine D1 and D2 receptor affinity. Isochromans and carbocyclic analogues had high D1 receptor affinity. Poor affinity for the chromans was attributed to an intramolecular hydrogen bond, which disrupts the ligand-receptor hydrogen bonding network.

Facile synthesis of octahydrobenzo[h]isoquinolines: Novel and highly potent D1 dopamine agonists

The octahydrobenzo[h]isoquinoline scaffold is of interest as a conformationally-restricted phenethylamine that may be useful for constructing biologically active products. Surprisingly, however, no tractable synthesis of this ring system has been reported

OCTAHYDROBENZOISOQUINOLINE MODULATORS OF DOPAMINE RECEPTORS AND USES THEREFOR

Octahydrobenzoisoquinoline modulators of dopamine receptors are described herein. Methods for using octahydrobenzoisoquinoline modulators of dopamine receptors in the treatment of dopamine dysfunction are also described herein.

Synthesis and reactivity of the catechol metabolites from the equine estrogen, 8,9-dehydroestrone

The risk factors for women developing breast and endometrial cancers are all associated with a lifetime of estrogen exposure. Estrogen replacement therapy in particular has been correlated with an increased cancer risk. Previously, we showed that the equine estrogens equilin and equilenin, which are major components of the widely prescribed estrogen replacement formulation Premarin, are metabolized to highly cytotoxic quinoids which caused oxidative stress and alkylation of DNA in vitro [Bolton, J. L., Pisha, E., Zhang, F., and Qiu, S. Chem. Res. Toxicol. 1998, 11, 1113-1127]. In this study, we have synthesized 8,9-dehydroestrone (a third equine estrogen component of Premarin) and its potential catechol metabolites, 4-hydroxy-8,9-dehydroestrone and 2-hydroxy-8,9-dehydroestrone. Both 2-hydroxy-8,9-dehydroestrone and 4-hydroxy-8,9-dehydroestrone were oxidized by tyrosinase or rat liver microsomes to o-quinones which reacted with GSH to give one mono-GSH conjugate and two di-GSH conjugates. Like endogenous estrogens, 8,9-dehydroestrone was primarily converted by rat liver microsomes to the 2-hydroxylated rather than the 4-hydroxylated o-quinone GSH conjugates; the ratio of 2-hydroxy-8,9-dehydroestrone versus 4-hydroxy-8,9-dehydroestrone was 6:1. Also in contrast to experiments with equilin, 4-hydroxyequilenin was not observed in microsomal incubations with 8,9-dehydroestrone or its catechols. The behavior of 2-hydroxy-8,9-dehydroestrone was found to be more complex than 4-hydroxy-8,9-dehydroestrone as GSH conjugates resulting from 2-hydroxy-8,9-dehydroestrone were detected even without oxidative enzyme catalysis. Under physiological conditions, 2-hydroxy-8,9-dehydroestrone isomerized to 2-hydroxyequilenin to form the very stable 2-hydroxyequilenin catechol; however, 4-hydroxy-8,9-dehydroestrone was found to be stable under similar conditions. Finally, preliminary studies conducted with the human breast tumor S-30 cell lines demonstrated that the catechol metabolites of 8,9-dehydroestrone were much less toxic than 4-hydroxyequilenin (20-40-fold). These results suggest that the catechol metabolites of 8,9-dehydroestrone may have the ability to cause cytotoxicity in vivo primarily through formation of o-quinones; however, most of the adverse effects of Premarin estrogens are likely due to formation of 4-hydroxyequilenin o-quinone from equilin and equilenin.

Inhibitors of Bllod Platelet Aggregation. Activity of Some 1H-Benzisoquinolinecarboximidamides on the in Vivo Blood Platelet Aggregation Induced by Collagen

A series of 33-1H-benzisoquinolinecarboximidamides has been prepared and tested in the rat after intraperitoneal (ip) and/or oral (po) administration for their ability to inhibit the in vivo blood platelet aggregation induced by colagen.In this aggregation test, a considerable number of active compounds were found.Fourteen compounds were active when administred ip , five of which also exhibited significant po activity.One compound was toxic after ip administration but was found to be active after po administration without apparent toxicity.Itis thought that the solubility of the drug in water is an important factor for the resorption after oral administration and, hence, for its oral activity.