Prodrug derivatives of 9.beta.-D-arabinofuranosyl-2-fluoroadenin

Drug – bio-affecting and body treating compositions – Conjugate or complex of monoclonal or polyclonal antibody,... – Conjugated via claimed linking group – bond – chelating agent,...

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536 26, 536 27, A61K 3170, C07H 1918, C07H 1920

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active

043573240

ABSTRACT:
The 5'-formate and the 5'-phosphate derivatives of 9-.beta.-D-arabinofuranosyl-2-fluoroadenine have been prepared as prodrug forms of the anti-cancer agent 9-.beta.-D-arabinofuranosyl-2-fluoroadenine, known as F-ara-A. These derivatives are quite water soluble whereas F-ara-A itself is sparingly soluble in water or in any organic solvents. Delivery of these prodrug forms to mice with L1210 leukemia results in the formation of higher levels of the triphosphate of F-ara-A, the active form of the drug, in the target L1210 leukemia cells. These prodrug forms are much more active chemotherapeutically than 9-.beta.-D-arabinofuranosyladenine, known as ara-A, and equivalent in activity to the combination of ara-A and 2'-deoxycoformycin, known as 2'-dCF, an effective in vivo inhibitor of adenosine deaminase, a ubiquitous enzyme that destroys ara-A in vivo.

REFERENCES:
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patent: 4123609 (1978-10-01), Behnke et al.
patent: 4136175 (1979-01-01), Rideout et al.
patent: 4188378 (1980-02-01), Montgomery
patent: 4210745 (1980-07-01), Montgomery
Repta et al., "Jour. Phar. Science", 64 pp. 392-396, 1975.

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