Synthesis, renal vasodilator and dopamine-sensitive adenylate cyclase activities of O-Methyl derivatives of 6-chloro-2,3,4,5-tetr ahydro-1-(4-hydroxyphenyl)-1H-3-benzazepin-7,8-diol (SK&F 82526)

doi:10.1002/JHET.5570230641

Paper

Synthesis, renal vasodilator and dopamine-sensitive adenylate cyclase activities of O-Methyl derivatives of 6-chloro-2,3,4,5-tetr ahydro-1-(4-hydroxyphenyl)-1H-3-benzazepin-7,8-diol (SK&F 82526)

Published Nov 1, 1986 · S. Ross, R. G. Franz, J. W. Wilson

Journal of Heterocyclic Chemistry

Q3 SJR score

12

Citations

0

Influential Citations

Full textSemantic Scholar

Abstract

The three possible mono-O-methyl derivatives of 6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepin-7,8-diol (SK&F 82526) (1) have been synthesized to facilitate the isolation and characterization of metabolites of this compound and for biological testing. The syntheses generally involved preparation of appropriately substituted benzaldehydes, conversion of these to phenylacetic acids and use of these to N-acylate arylethanolamines. The phenylacetamides thus formed were reduced to amines and these were deprotected and cyclized to the desired final products. In one case deprotection followed cyclization. These compounds were tested as activators of dopamine-sensitive adenylate cyclase (a measure of DA-1 agonist activity) and as renal vasodilators. All three O-methyl derivatives were much less potent than 1 in cyclase activation and as renal vasodilators. Weak inhibition of adenyl cyclase was also observed for all three compounds and one showed weak renal vasoconstrictor activity. Preliminary investigation of the metabolism of 1 disclosed that two of the three monomethoxy compounds were formed in trace amounts in the rat and the dog. In a related investigation, the trimethoxy derivative of 1 was subjected to acid-catalyzed hydrolysis conditions. The relative ease of cleavage of methoxy groups was 7 > > 4′ > 8.

In Vitro Study

Study Snapshot

O-methyl derivatives of 6-chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepin-7,8-diol show less potent activation of dopamine-sensitive adenylate cyclase and weak

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

Synthesis, renal vasodilator and dopamine-sensitive adenylate cyclase activities of O-Methyl derivatives of 6-chloro-2,3,4,5-tetr ahydro-1-(4-hydroxyphenyl)-1H-3-benzazepin-7,8-diol (SK&F 82526)

Sign up to use Study Snapshot

References

A new oral renal vasodilator, fenoldopam

Fenoldopam is an effective oral renal vasodilator in humans, increasing urine volume, free water clearance, and sodium fractional excretion by stimulating renal dopamine receptors.

Dopamine-sensitive adenylyl cyclase in human caudate nucleus. A study in control subjects and schizophrenic patients.

Dopamine-sensitive adenylyl cyclase activity in the caudate nucleus of the human brain is not different between control subjects and schizophrenic patients.

Adenosine 3',5'-monophosphate concentrations and isoproterenol-induced synthesis of deoxyribonucleic acid in mouse parotid gland.

In mouse parotid gland, cyclic 39,59-AMP plays a role in accelerating DNA synthesis induced by isoproterenol, with increased cyclic 39,59-AMP concentrations preceding DNA synthesis changes.

Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the "dopamine receptor".

Dopamine-sensitive adenylate cyclase may be the receptor for dopamine in the mammalian brain, potentially facilitating the search for new therapeutic agents for treating extrapyramidal diseases.

Herstellung von Mandelaldehyden durch katalytische Hydrierung von Mandelsäurenitrilen mit Raney-Nickel in Gegenwart von Schwefelsäure

Catalytic hydrogenation of Mandelonitriles over Raney nickel in the presence of sulphuric acid allows partial hydrogenation of aromatic cyanohydrins to mandelaldehydes, with an improved method for preparing cyanohydrins.

Citations

Cefiderocol (S-649266), A new siderophore cephalosporin exhibiting potent activities against Pseudomonas aeruginosa and other gram-negative pathogens including multi-drug resistant bacteria: Structure activity relationship.

Cefiderocol (S-649266) is a promising parenteral cephalosporin with potent activities against multi-drug resistant Gram-negative pathogens, including carbapenem resistant bacteria.

Selective esterification of the polyphenol resveratrol at the 4′-position

Selective esterification of resveratrol at the 4′-position using NaH and acid anhydrides allows for the generation of extended 4′-phenolate anion, with minimal formation of 3-monoester, 3,5-diester, and triester products.

Studies on Paraherquamide Biosynthesis: Synthesis of Deuterium-Labeled 7-Hydroxy-Pre-Paraherquamide, a Putative Precursor of Paraherquamides A, E & F.

The synthesis of deuterium-labeled 7-hydroxy-pre-paraherquamide (27) suggests a potential intermediate in paraherquamide biosynthesis, but its biosynthetic intermediacy remains in question.

Stereocontrolled total synthesis of (−)-aspidophytine

The enantioselective stereocontrolled total synthesis of ()-aspidophytine was achieved using a key indole intermediate, cyclic amine precursor, and lactone ring formation.

Enantioselective total synthesis of aspidophytine.

This study presents an enantioselective total synthesis of aspidophytine using radical cyclization, Sonogashira coupling, and functionalized acetylene units, resulting in the aspidosperma skeleton and lactone ring.

Chemical degradation products of lignin and humic substances Part II Synthesis, structure verification and liquid chromatographic separation of chlorinated protocatechualdehydes (3,4-dihydroxy-benzaldehydes), 5-hydroxyvanillins (3,4-dihydroxy-5-methoxy-benzaldehydes) and gallaldehydes (3,4,5-trihydr

Chlorinated protocatechualdehydes, 5-hydroxyvanillins, and gallaldehydes were synthesized and characterized for purity and structure using liquid chromatography and mass spectrometry.

Determination of chlorinated benzaldehydes and acetophenones in pulp bleaching effluents by gas chromatography

Chlorinated benzaldehydes and acetophenones are major compounds in pulp bleaching effluents, and the DB5 column is useful for analyzing these compounds by gas chromatography.

The synthesis of octahydro-7-phenylpyrazino[2,1-b][3]benzazepines

Octahydro-7-phenylpyrazino[2,1-b][3]benzazepines can be synthesized from 1-methyl-3-phenylmethylpiperazine, 1-methyl-3-(3-chloro-4-methoxyphenyl)piperazine, and 2-