Dihydro(alkylthio)(naphthylmethyl)oxopyrimidines: novel non-nucleoside reverse transcriptase inhibitors of the S-DABO series.
J Med Chem
; 40(10): 1447-54, 1997 May 09.
Article
in En
| MEDLINE
| ID: mdl-9154967
ABSTRACT
Novel compounds related to 2-(cyclohexylthio)-3,4-dihydro-5-methyl-6-(3-methylbenzyl)-4-ox opyrimidine (3c, MC 639) have been synthesized and tested as inhibitors of human immunodeficiency virus type-1 (HIV-1). Reaction of thiourea with ethyl arylmethylacetoacetates furnished 5-alkyl-6-(arylmethyl)-3,4-dihydro-2-mercapto-4-oxopyrimidines which were then alkylated at the sulfur atom to afford the required 2-alkylthio or 2-cycloalkylthio derivatives (S-DABOs). Chemical modifications at N-3, C-4, and C-6 of the pyrimidine ring were attempted with the aim of improving antiretroviral activity. In particular, replacement of the benzyl group with the 1-naphthylmethyl moiety enhanced the activity of S-DABOs, whereas N-3 alkylation and C=O transformation into C=S at position 4 of the pyrimidine ring led to compounds devoid of anti-HIV-1 activity. Lower activity was generally observed when 1-naphthylmethyl was replaced by the isomeric 2-naphthylmethyl moiety. The most active compounds showed activity in the low micromolar range with EC50 values comparable to that of nevirapine.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrimidines
/
Reverse Transcriptase Inhibitors
/
HIV Reverse Transcriptase
Limits:
Humans
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
1997
Type:
Article
Affiliation country:
Italy