Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1997-01-14
2000-03-21
Kight, John
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 48, 514 51, 536 2623, A61K 3170, C07H 19207
Patent
active
060402970
DESCRIPTION:
BRIEF SUMMARY
This invention relates to dinucleoside-5',5'-P.sup.1,P.sup.2 -pyrophosphates of the formula (I): ##STR1## wherein: the symbols A and B each independently represent a 5'-C' radical of a non-naturally occurring nucleoside selected from thymine-3'-azido-2',3'-dideoxy-D-riboside, 5-fluorouracil-2'-deoxy-D-riboside, uracil-3'-azido-2',3'-dideoxy-D-riboside, guanine-2',3'-dideoxy-D-riboside, hypoxanthine-2',3'-dideoxy-D-riboside, cytosine-2',3'-dideoxy-D-riboside, and adenine-2',3'-dideoxy-D-riboside; group of from 1 to 10 carbon atoms; R.sub.1 represent hydrogen with bases providing biologically acceptable cations.
This invention includes also a process for the preparation of the dinucleoside-5',5'-P.sup.1,P.sup.2 -pyrophosphates of formula (I), a method for their encapsulation into biological carriers, in particular erythrocytes, for targeting the above compounds to specific sites or cell populations which are involved in the development or responsible of pathological disorders such as tumors or viral infections, and compositions containing said biological carriers, in particular erythrocytes, encapsulating the dinucleoside-5',5'-P.sup.1,P.sup.2 -pyrophosphates of formula (I).
Chemical modification of the erythrocytic membrane to encapsulate biologically active molecules is a powerful method to deliver to target cells the encapsulated molecule in a biologically active form. See, for instance; The Year in Immunology, Basel, Karger, (1993), Vol. 7, 168-174. doxorubicin". Eur. J. Cancer, (1991), Vol. 27, No. 7, 947-948. the antineoplastic drug 5-fluoro-2'-deoxyuridine". Advances in Biosciences, (1991), Vol. 81, Pergamon Press plc. 51-57. 5-fluoro-2'-deoxyuridine-5'-monophosphate to the antineoplastic drug 5-fluoro-2'-deoxyuridine in human erythrocytes". Proc. Natl. Acad. Sci. USA, (1988), Vol. 85, 3145-3149. tool for diagnosis and therapy". Biotechnology in Diagnostics, Elsevier Science Publishers B.V., (1985), 223-236.
Further literature in the field is cited in the above mentioned articles and publications.
In the following description and claims the correspondence between chemical names and commonly used acronyms will be maintained, as reported below: adenine-2',3'-dideoxy-D-riboside (DDA), 5-fluorouracil-2'-deoxy-D-riboside (FDU), cytosine-2',3'-dideoxy-D-riboside (DDC), uracil-3'-azido-2',3'-dideoxy-D-riboside (AZDDU), hypoxanthine-2',3'-dideoxy-D-riboside (DDI), and guanine-2',3'-dideoxy-D-riboside (DDG).
Methods of encapsulating biologically active substances, in particular, phosphorylated compounds, into transformed erythrocytes and compositions for their use, as well as methods for inducing animal derived cells, especially erythrocytes to selectively seek out and fuse with other cells, have been disclosed also in patent literature: International Patent Application Publication No. 92/22306, U.S. Pat. No. 4,931,276, U.S. Pat. No. 4,652,449 and European Patent Application Publication No. 298280.
International Patent Application Publication No. WO 91/00867 describes 5'-diphosphohexose nucleosides having biological activity including antiviral activity.
In this description and claims, the expression "5'-C' radical of a non-naturally occurring nucleoside" identifies a radical derived from a non-naturally occurring nucleoside by removal of the hydroxy group in position 5' of the pentose moiety.
The expression "the symbols X each independently represent oxygen or sulfur" means that each of the symbols X may represent an oxygen or sulfur atom independently of the meanings assumed by the others. According to a preferred embodiment of this invention, either all symbols X represent oxygen or only one or two of them represent(s) sulfur and the others represent oxygen. In this latter case, the most preferred compounds of formula (I) are those wherein the symbol(s) X representing sulfur is(are) that(those) directly linked to the phosphorus atom(s) through a double bond or that(those) which is(are) part of the moiety XR or(and) XR.sub.1.
The term "a biologically acceptable cation" means a cation which is suitable for th
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Benatti Umberto
De Flora Antonio
Giovine Marco
Biosearch Italia S.p.A.
Crane L. Eric
Gruppo Lepetit S.p.A.
Kight John
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