In:
Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 80, No. 3 ( 2002-03-01), p. 198-204
Abstract:
A series of nine (±)-nantenine derivatives were synthesized and assayed for their pharmacological activities by using tension in aorta and binding experiments in rat brain membrane. Replacing a methyl group with a hydrogen ((±)-nornantenine) and an ethyl group at a nitrogen atom ((±)-ethylnornantenine) or introducing a hydroxyl group at the α/β position of C-4 or displacement of a methoxy moiety at the C-1 position with a hydroxyl ((±)-domesticine) of (±)-nantenine decreased the affinity. Moreover, changing a methyl group of (±)-domesticine to hydrogen at a nitrogen atom ((±)-nordomesticine) caused loss of the activities. These results suggest that a methyl group at a nitrogen atom and a methoxy moiety at C-1 play important roles in the development of the antiserotonergic activity. Molecular modeling analysis of the interaction between the 5-HT 2A receptor and (±)-nantenine suggested that electron lone pairs of N-6 and of the oxygen atom of the methoxy group at C-1 are important in forming a hydrogen bond to Asp155 and Asn343 of the 5-HT 2A receptor, respectively.Key words: antiserotonergic activity, (±)-nantenine derivative, SAR, molecular modeling.
Type of Medium:
Online Resource
ISSN:
0008-4212
,
1205-7541
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
2002
detail.hit.zdb_id:
2004356-9
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