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.

Abstract:

:Novel derivatives of 4-oxo-3-methylcytisine with phenyl moiety bonded to starting molecule through various spacers were obtained from the 9-amino, -halo, -formyl and 11-halo precursors by reductive alkylation of amines, generation of amide, as well as thio- and carboxamide functions, cross-coupling reactions, aldehyde condensation and reduction of unsaturated 'C-C' bonds. Ability of synthesized compounds to influence the learning and memory was preliminary assessed in conditioned passive avoidance reflex (CPAR) test in rats. It was shown, that derivatives with phenyl group at 11 carbon atom influence the learning and memory in CPAR test more effectively than other compounds. The hit-compound (3-methyl-11-(2-phenylvinyl)-3,5,6-trihydro-2H-1,5-methanopyrido[1,2-a][1,5]diazocine-4,8(1H)-dione) with the best values of 'latency' and 'time spent in the dark compartment' has been identified as a perspective scaffold for synthesis of novel derivatives of (-)-cytisine with potential neuropharmacological activity.

journal_name

Nat Prod Res

journal_title

Natural product research

authors

Tsypysheva I,Petrova P,Koval'skaya A,Lobov A,Sapozhnikova T,Makara N,Gabdrakhmanova S,Zarudii F

doi

10.1080/14786419.2019.1622106

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

207-215

issue

2

eissn

1478-6419

issn

1478-6427

journal_volume

35

pub_type

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