indole,15 pyrrole,16 pyridine,17 isothiazole,18 isoselenoazole,18
quinoline,19 furan,16 benzothiophene,20 or pyridothiophene21 have
been described in the literature. Although the thiophene ring is
considered as a bioisoster of the benzene ring, the synthesis
and chemistry of thiophene analogues of 3,4-dihydrobenzo[1,4]-
diazepine-2,5-diones have been less studied. Nevertheless, the
thieno[1,4]diazepine moiety is found in clotiazepam (Figure 1),
an orally active anxiolytic and tenxiolytic drug.22,23 Tricyclic
structures derived from the later are further described24-26 and
include etizolam (Figure 1), an anticonvulsing and muscle
relaxing agent,27,28 and Y-24180 (Figure 1), a specific antagonist
of platelet activating factor.29,30
Reactivity Study of
1H-Thieno[3,2-d][1,3]oxazine-2,4-dione toward the
Synthesis of Bicyclic
3,4-Dihydro-1H-thieno[3,2-e][1,4]diazepine-2,5-dione
Analogues
Yann Brouillette, Vincent Lisowski,* Pierre Fulcrand, and
Jean Martinez
Laboratoire des Aminoacides, Peptides et Prote´ines (LAPP),
CNRS UMR 5810, UMI-UMII, UFR des Sciences
Pharmaceutiques et Biologiques, 15 AVenue Charles Flahault,
34093 Montpellier Cedex 5, France
Vincent.lisowski@uniV-montp1.fr
ReceiVed NoVember 6, 2006
A series of 10 optically pure 3,4-dihydro-1H-thieno[3,2-e]-
[1,4]diazepine-2,5-dione derivatives has been synthesized in
41-75% yields on treatment of 1H-thieno[3,2-d][1,3]oxazine-
2,4-dione with different natural R-amino acids.
FIGURE 1. Representative examples of bioactive thienodiazepines.
While synthetic routes to bicyclic thieno[2,3-e][1,4]diazepine
have been described,31,32 mainly from (2-aminothiophen-3-yl)-
3,4-Dihydrobenzo[1,4]diazepine-2,5-diones are known as
potential antitumor compounds,1-4 antiamebics,5 antithrombot-
ics,6 bactericides,7 and herbicides.8 3,4-Dihydro[1,4]diazepine-
2,5-diones fused with a heterocycle such as imidazole,9-14
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10.1021/jo0622882 CCC: $37.00 © 2007 American Chemical Society
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