Title: Novel 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine derivatives as non-nucleoside reverse transcriptase inhibitors that inhibit human immunodeficiency virus type 1 replication
Authors: Arranz, E ×
Díaz, J A
Ingate, S T
Witvrouw, Myriam
Pannecouque, Christophe
Balzarini, Jan
De Clercq, Erik
Vega, S #
Issue Date: Oct-1998
Series Title: Journal of Medicinal Chemistry vol:41 issue:21 pages:4109-17
Abstract: The 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazines (TTDs) represent a recently discovered chemical class of non-nucleoside reverse transcriptase inhibitors that selectively block human immunodeficiency virus type 1 replication. In a search for a better understanding of their mode of binding and with the aim of obtaining novel lead compounds, a second series of TTD derivatives was synthesized and evaluated for antiviral activity. The design of the new compounds was based on a variety of chemical modifications which were carried out in the original prototype 20a (QM 96521). Substitution of a halogen at the meta position of the N-2 benzyl group resulted in an improvement of the antiviral activity by 1 order of magnitude. Compounds bearing at the N-4 position a cyanomethyl, propargyl, or benzyl substituent were found to be the most potent of the series. Modifying the thieno[3,4-e] ring fused to the 1,2,4-thiadiazine moiety to other heterocyclic ring systems decreased the potency. The results obtained in this investigation have provided new indications for the design of even more effective TTDs.
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Molecular Virology and Gene Therapy
× corresponding author
# (joint) last author

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