PYRIDO ANALOGS OF PSYCHOPHARMACOLOGICAL AGENTS
Date
1973
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Doctoral
Abstract
The intramolecular nucleophilic cyclization of 3-pyridyl-alkylamines onto the 2-position of the pyridine ring was invest-igated using a wide variety of experimental conditions. The optimum conditions determined for cyclization were pulverized sodium in toluene at reflux for 72 hours. Two bicyclic products, 6,7,8,9-tetrahydro-5H-pyrido[2,3-b]azepine and 1,2,3,4-tetrahydro- 1,8-naphthyridine, were prepared in good yield.
Aralkylhydrazines are known to be MAO inhibitors. Only one 3-pyridylalkylhydrazine has been previously reported and tested for MAO inhibition. A series of 3-pyridylalkylhydrazines were prepared and their hydrochloride salts were tested for MAO inhibitory activity in both in vivo and in vitro methods. All three showed MAO inhibitory activity. In the in vitro screen 2-(3-pyridyl)ethylhydrazine was as active as the marketed benzene isostere phenelzine.
1,4-Benzodiazepines are marketed as central nervous system depressants. Only one pyrido[2,3-e]-1,4-diazepine has been reported in the literature. It was not clear if this compound was tested for pharmacological activity. A series of pyrido- [2,3-e]-1,4-diazepines was attempted to be synthesized by repeating the literature synthesis from 2-amino-3-benzoylpyridine. However, problems were encountered and no pyrido[2,3-2J-1,4-diazepine was isolated. Presumably hydrolysis occurred in one of the steps resulting in the isolation of the starting material.
The novel intramolecular nucleophilic cyclization of 3-pyridylalkylamines was applied in an attempt to prepare pyrido-[2,3-e]-1,4-diazepines. Side chain imines were prepared from nicotinaldehyde with N-methylethylenediamine and ethylenediamine. Cyclization of the N-methylimine and the saturated N-methyl-ethylenediamine derivatives were attempted, but gave discouraging results. The ethylenediamine derivative was also prepared, but once again the cyclization failed to occur. It was planned to prepare 5-phenylpyrido[2,3-fj-1,4-diazepines by using 3-benzoyl-pyridine as starting material. However, since the above route starting with nicotinaldehyde was unsuccessful only the conden-sation of 3-benzoylpyridine with N-methylethylenediamine is reported in this work. In the attempted cyclization of N-(3-picolyl)ethylenediamine intermediates were suspected and further
work in this area will probably result in the formation of the desired ring system.
The use of 2-amino-3-benzoylpyridine for the synthesis of 3-substituted-2-amino-4-phenyl-1,8-naphthyridines was investigated. Two new derivatives were prepared as analogs of the pteridine diuretic, triamterene.
Description
Keywords
MAO inhibition, 3-pyridyl- alkylamines
Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Pharmacy and Nutrition