Cognition-activating properties of 3-(aryloxy)pyridines

Journal of Medicinal Chemistry
1981.0

Abstract

A series of 3-(aryloxy)pyridines was found to possess activity in enhancing retention for passive avoidance learning in mice. This test was used to select compounds with potential therapeutic properties for the treatment of cognitive disorders. Reference drugs that gave positive results in this procedure included d-amphetamine, magnesium pemoline, methyl phenidate, picrotoxin, phenytoin, and ethosuximide. All active compounds gave inverted U-shaped dose-response curves. The most active compounds of the 3-(aryloxy)pyridines included 3-phenoxypyridine (1), 3-(2-fluorophenoxy)pyridine (2), 3-(4-fluorophenoxy)pyridine (4), 3,3'-oxybis(pyridine) (23), and 3,3'-oxybis(pyridine) 1-oxide (24). 3-Phenoxypyridine (1) was clearly superior to all of the analogues tested in terms of the level of retention, grammometric potency, and the breadth of its inverted U-shaped dose-response curve. It was given the designation of CI-844 and after a detailed study of its pharmacological profile was submitted for preclinical toxicology.

Knowledge Graph

Similar Paper

Cognition-activating properties of 3-(aryloxy)pyridines
Journal of Medicinal Chemistry 1981.0
Variation of spacer type and topology of phenyl moiety in 2-pyridone core of 4-oxo-3-N-methylcytisine; effect of synthesized compounds on rat’s behavior in conditioned passive avoidance reflex (CPAR) test
Natural Product Research 2021.0
Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl]-2-oxo-1-pyrrolidineacetamides, including pramiracetam
Journal of Medicinal Chemistry 1984.0
Benzodiazepine receptor binding and anticonflict activity in a series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines devoid of anticonvulsant properties
Journal of Medicinal Chemistry 1985.0
3-Phenylpiperidines. Central dopamine-autoreceptor stimulating activity
Journal of Medicinal Chemistry 1981.0
3-[(2-Ethoxyphenoxy)methyl]piperidine derivatives. Synthesis and antidepressant activity
Journal of Medicinal Chemistry 1987.0
Synthesis, biochemical activity and behavioral effects of a series of 1,4,5,6-tetrahydropyrimidines as novel ligands for M1 receptors
Bioorganic & Medicinal Chemistry Letters 1992.0
Potent anticonflict activity and lessening of memory impairment with a series of novel [1]benzothieno[2,3-c]pyridines and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines
Journal of Medicinal Chemistry 1990.0
3-(Aminoalkyl)-1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones as potential anticholinergic bronchodilators
Journal of Medicinal Chemistry 1989.0
Further exploration of an N-aryl phenoxyethoxy pyridinone-based series of mGlu3 NAMs: Challenging SAR, enantiospecific activity and in vivo efficacy
Bioorganic & Medicinal Chemistry Letters 2019.0