- Anti-cancer drug aldehyde conjugate drugs with enhanced cytotoxicity compounds, compositions and methods
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Monomeric and dimeric anti-cancer drug aldehyde conjugate compounds and pharmaceutically acceptable salts thereof. Specifically, monomeric and dimeric aldehyde conjugates of 1-2, dihetero-substituted anti-cancer drugs, including monomeric and dimeric aldehyde conjugates of anthracyclines, are provided. Also provided are pro-drugs which, after administration, release monomeric aldehyde conjugates. Further provided are pharmaceutical and therapeutic compositions containing anti-cancer drug aldehyde conjugates and methods of treating cancer using the aldehyde conjugates.
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Page/Page column 17; 18; 56
(2010/02/05)
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- Coumarin and related aromatic-based polymeric prodrugs
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The present invention is directed to double prodrugs containing polymeric-based transport forms. These polymeric prodrugs are preferably of the formula: wherein: B is H, OH, OSiR13, a residue of an amine-containing target moiety or a residue of a hydroxyl-containing target moiety, G is or CH2; Y1-2are independently O or S; M is X or Q; where X is an electron withdrawing group and Q is a moiety containing a free electron pair positioned three to six atoms from C(═Y2); R1, R4, R7, R8, R9, R10and R13are independently one of hydrogen, C1-6alkyls, C3-12branched alkyls, C3-8, cycloalkyls, C1-6substituted alkyls, C3-8substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6heteroalkyls, substituted C1-6heteroalkyls, C1-6alkoxy, phenoxy, C1-6heteroalkoxy, except that R1and R4can also be a cyano, nitro, carboxyl, acyl, substituted acyl, carboxyalkyl; Ar is a moiety which when included in Formula (I) forms a multi-substituted aromatic hydrocarbon or a multi-substituted heterocyclic group; (m) is zero or one; (n) is zero or a positive integer; (p) is zero, one or two; (q) is three or four; and R11is a substantially non-antigenic polymer.
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- HEMISYNTHESE DE NOUVEAUX GLICOSIDES ANALOGUES DE LA DAUNORUBICINE
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Seven daunorubicin analogs containing α-L-, α-D-, and β-D-glicosidic linkages, in which the natural occuring sugar (L-daunosamine) was replaced by diastereomeric 3-amino-2,3,6-trideoxyhexoses (3-epi-L-daunosamine, D-acosamine, D-daunosamine, D-ristosamine, and 3-epi-D-daunosamine), were prepared.In all cases, glycosidation with daunomycinone was performed in the presence of p-toluenesulfonic acid starting from 1-O-acetyl-2,3,6-trideoxy-4-O-p-nitrobenzoyl-3-trifluoro-acetamidohexopyranoses (prepared from the corresponding methyl 3-amino-2,3,6-trideoxyhexopyranosides) or from 1,5-anhydro-2,3,6-trideoxy-4-O-p-nitrobenzoyl-3-trifluoroacetamidohex-1-enitols (prepared from glycosals or pseudoglycals, the 3-amino group being introduced by substitution with sodium azide and subsequent reduction).Glycosidation was followed by removal of the protecting groups.
- Boivin, Jean,Montagnac, Alain,Monneret, Claude,Pais, Mary
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p. 223 - 242
(2007/10/02)
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- Process for preparing daunomycin and analogues thereof
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Racemic anthracyclinones of the general formula II STR1 when condensed with 2,3,6-trideoxy-3-trifluoroacetamido-4-0-trifluoroacetyl-α-L-lyxo-pyranosyl chloride in the presence of silver trifluoromethane sulphonate yield an easily separable mixture of equimolar amounts of exclusively the α-glycoside of the 7S : 9S diastereomer and the β-glycoside of the 7R : 9R diastereomer. In this way the biologically important α-glycosides of the 7S : 9S diastereomer of the general formula I (below) are easily prepared from a racemic anthracyclinone.
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- Process for the preparation of daunorubicin by cultivating a streptomyces species
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The antibiotic daunorubicin is prepared by aerobically cultivating the microorganism Streptomyces griseus, var. rubidofaciens, DS 32,041 (NRRL 3383), or a daunorubicin-producing mutant thereof, using an aqueous nutrient medium containing assimilable sources of carbon, nitrogen and inorganic substances, and separating daunorubicin formed during the culture.
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