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Synthesis and anti‐HIV‐1 activity of a series of 1‐(alkoxymethyl)‐5‐alkyl‐6‐(arylselenenyl)uracils and ‐2‐thiouracils
Author(s) -
Kim DaeKee,
Kim YoungWoo,
Gam Jongsik,
Kim Ganghyeok,
Lim Jinsoo,
Lee Namkyu,
Kim HunTaek,
Kim Key H.
Publication year - 1996
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570330446
Subject(s) - lithium diisopropylamide , chemistry , uracil , trimethylsilyl , alkyl , amide , diselenide , substituent , hydrolysis , medicinal chemistry , stereochemistry , oxonium ion , nitrosation , organic chemistry , selenium , biochemistry , dna , ion , deprotonation
A series of 1‐(alkoxymethyl)‐5‐alkyl‐6‐(phenylselenenyl)uracils and ‐2‐thiouracils modified at the 3‐ and/or 5‐position of the C‐6 phenylselenenyl ring with methyl or fluoro substituent has been synthesized and tested for their ability to inhibit HIV‐1 replication. Lithiation of the acyclic uracil and 2‐thiouracil derivatives 11‐14 and 27‐32 with lithium diisopropylamide or lithium bis(trimethylsilyl)amide followed by reaction with an appropriate diaryl diselenide afforded 6‐arylselenenyl compounds 18‐26 after removal of the tert ‐butyldimethylsilyl protecting group and 35‐47 . Compounds 48‐54 were prepared from compounds 38‐44 by oxidative hydrolysis of the thione function. Of these compounds, 50 inhibited HIV ‐1 replication in human T 4 lymphoblastoid cells at a 50% effective concentration (EC 50 ) of 0.0047 μ M with a selectivity index of >42600.