Anti-tumor compounds, pharmaceutical compositions, methods for preparation thereof and for treatment
AssigneeThe Research Foundation of State University of New York
InventorsIwao Ojima, Ezio Bombardelli
Life of this patent
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Abstract
The present invention is directed to novel taxanes useful as chemotherapeutic agents or their precursors. Processes for preparing the novel taxanes include coupling reactions, in the presence of a base, of baccatin of formula (III) or (IV) ##STR1## with .beta.-lactams of formula (V). ##STR2## The invention also provides pharmaceutical compositions including the novel taxanes and method for treatment of certain cancers with these new compounds.
Claims8
A compound of the formula (I) ##STR15## wherein R.sup.1 is an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl radical, an unsubstituted or substituted aryl or heteroaryl radical, an unsubstituted or substituted cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocycloalkenyl radical;
- R.sup.2 is an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl radical;
- or R.sup.2 is an RO--, RS-- or RR'N-- wherein R is an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl radical;
- R' is a hydrogen or R as defined above;
- R and R' can be connected to form a cyclic structure;
- R.sup.3 is a hydrogen or an acyl or an alkyl or an alkenyl or an alkynyl or an unsubstituted or substituted cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocycloalkenyl radical, or an unsubstituted or substituted aryl or heteroaryl radical or a hydroxyl protecting group;
- R.sup.4 is a hydrogen or an acyl radical or an alkyl, alkenyl or alkynyl radical, an unsubstituted or substituted cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocycloalkenyl radical, an unsubstituted or substituted aryl or heteroaryl radical, or a hydroxyl protecting group;
- R.sup.5 is a hydrogen or an acyl radical or an alkyl, alkenyl or alkynyl radical, an unsubstituted or substituted cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocycloalkenyl radical, an unsubstituted or substituted aryl or heteroaryl radical, or a hydroxyl protecting group;
- R.sup.6 is a hydrogen or an acyl radical or an alkyl, alkenyl or alkynyl radical, an unsubstituted or substituted cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocycloalkenyl radical, an unsubstituted or substituted aryl or heteroaryl radical, or a hydroxyl protecting group;
- R.sup.5 and R.sup.6 can be connected to form a cyclic structure;
- R.sup.7 is an acyl group;
- R.sup.8 is an hydrogen or a hydroxyl protecting group;
- wherein, whenever R.sup.1 is a phenyl radical, said phenyl radical is substituted with at least one halogen, hydroxyl, amino, mercapto, cyano, carboxyl group;
- alkoxy, alkylamino, dialkylamino, alkylthio, alkoxycarboxyl group wherein said alkyl portion has 1 to 15 carbon atoms;
- aryloxy, arylthio, aryloxycarbonyl, wherein said aryl portion has 6 to 20 carbon atoms;
- or heteroarylthio, heteroaryloxy carbonyl wherein said heteroaryl portion has 3 to 15 carbon atoms.
A compound of the formula (I) ##STR16## wherein R.sup.1 is an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl radical, an unsubstituted or substituted aryl or heteroaryl radical, an unsubstituted or substituted cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocycloalkenyl radical;
- R.sup.2 is an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl radical;
- or R.sup.2 is an RO--, RS-- or RR'N-- wherein R is an unsubstituted or substituted straight chain or branched alkyl, alkenyl or alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl radical;
- R' is a hydrogen or R as defined above;
- R and R' can be connected to form a cyclic structure;
- R.sup.3 is a hydrogen or an acyl or an alkyl or an alkenyl or an alkynyl or an unsubstituted or substituted cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocycloalkenyl radical, or an unsubstituted or substituted aryl or heteroaryl radical or a hydroxyl protecting group;
- R.sup.4 is a hydrogen or an acyl radical or an alkyl, alkenyl or alkynyl radical, an unsubstituted or substituted cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocycloalkenyl radical, an unsubstituted or substituted aryl or heteroaryl radical, or a hydroxyl protecting group;
- R.sup.5 is a hydrogen or an acyl radical or an alkyl, alkenyl or alkynyl radical, an unsubstituted or substituted cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocycloalkenyl radical, an unsubstituted or substituted aryl or heteroaryl radical, or a hydroxyl protecting group;
- R.sup.6 is a hydrogen or an acyl radical or an alkyl, alkenyl or alkynyl radical, an unsubstituted or substituted cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocycloalkenyl radical, an unsubstituted or substituted aryl or heteroaryl radical, or a hydroxyl protecting group;
- R.sup.5 and R.sup.6 can be connected to form a cyclic structure;
- R.sup.7 is an acyl group;
- R.sup.8 is an hydrogen or a hydroxyl protecting group;
- wherein R.sup.1 is a radical selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, isohexyl, heptyl, isoheptyl, octyl, isoctyl, cyclohexylmethyl, cyclohexylethyl, benzyl, phenylethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and adamantyl, vinyl, allyl, 2-phenylethenyl, 2-furylethenyl, 2-pyrrolyl-ethenyl, 2-pyridylethenyl, 2-thienylethyl, ethynyl, propargyl, tolyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-chlorophenyl, naphthyl, furyl, pyrrolyl, pyridyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, oxiranyl, pyrrolidinyl, piperidinyl, tetrahydrofuryl, tetrahydropyranyl, dihydrofuryl, dihydropyrrolyl, dihydropiranyl, and dihydropyridyl.
Dependencies are inferred from the claim text.