Diazepinone nucleosides as inhibitors of cytidine deaminase

Article abstract of DOI:10.1080/07328319608002457

The synthesis of 2'-deoxy and 2',3'-dideoxy derivatives of 1-β-D- ribofuranosyl-1,3,4,7-tetrahydro-2H-1,3-diazepin-2-one (2) was undertaken in order to find new cytidine deaminase (CDA) inhibitors and potential adjuvants in anticancer chemotherapy. Replacement of ribose by a 2-deoxyribose moiety led to compound 9 that appeared slightly more potent than 2 (Ki = 2.5 x 10^{- 8} M). Remarkably, the corresponding α-2'-deoxynucleoside 10 acted as a very potent inhibitor of human placenta CDA, with a Ki = 7.5 x 10^-8 M. Attempt to synthesize the 2',3'-dideoxy derivative of 2 led to N-[4,5-dihydroxy-1- (2-oxo-2,3,4,7-tetrahydro[1,3] diazepin-1-yl)-pentyl]-2,2,2- trifluoroacetamide (13), which is devoid of CDA inhibitory activity.

Full text of DOI:10.1080/07328319608002457

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Nucleosides and Nucleotides
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Diazepinone Nucleosides as Inhibitors of
Cytidine Deaminase.
G. Cristalli a , R. Volpini a , S. Vittori a , E. Camaioni a , G. Rafaiani a
, S. Potenza b & A. Vita a
a Dipartimento di Scienze Chimiche , Università di Camerino , 62032,
Camerino, Italy
b Dipartimento di Biologia Cellulare , Università di Camerino ,
62032, Camerino, Italy
Published online: 20 Aug 2006.
To cite this article: G. Cristalli , R. Volpini , S. Vittori , E. Camaioni , G. Rafaiani , S. Potenza
& A. Vita (1996) Diazepinone Nucleosides as Inhibitors of Cytidine Deaminase., Nucleosides and
Nucleotides, 15:10, 1567-1580, DOI: 10.1080/07328319608002457
To link to this article: http://dx.doi.org/10.1080/07328319608002457
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