Patent ID: 6369109
Filing Date: 2002-04-09
Classification: A61K,C07J

Abstract:
A compound having a structure: whereinR1 is selected from the group consisting of hydrogen, â€”SO3H, â€”PO3H2, â€”C1-C20 straight or branched chain alkyl, â€”C2-C20 straight or branched chain alkenyl, â€”C2-C20 straight or branched chain alkynyl, â€”(CH2CH2O)nH, â€”(CH2CH2O)nCH3, â€”(CH2CH2O)nCH2CH3, â€”C(O)C6H5, â€”C(O)C1-C20 straight or branched chain alkyl, â€”C(O)C2-C20 straight or branched chain alkenyl, â€”C(O)C2-C20 straight or branched chain alkynyl, myo-inosityl, scyllo-inosityl, a cyclitol, conduritol A, quebrachitol, a monosaccharide, a disaccharide and an oligosaccharide; the â€”(CH2CH2O)nH, myo-inosityl, scyllo-inosityl, cyclitol, conduritol A, quebrachitol, monosaccharide, disaccharide and oligosaccharide being optionally substituted with one or more â€”C(O)C1-C20 straight or branched chain alkyl, â€”C(O)C2-C20 straight or branched chain alkenyl, â€”C(O)C2-C20 straight or branched chain alkynyl, sulfate, or mono-, di- or tri-phosphate groups; R2 is selected from the group consisting of â€”CO2H, â€”CO2(C6H5), â€”CO2(C1-C20 straight or branched chain alkyl), â€”CO2(C2-C20 straight or branched chain alkenyl), â€”CO2(C2-C20 straight or branched chain alkynyl), â€”CO2(myo-inosityl), â€”CO2(scyllo-inosityl), â€”CO2(cyclitol), â€”CO2(conduritol A), â€”CO2(quebrachitol), â€”CO2(monosaccharide), â€”CO2(disaccharide), â€”CO2(oligosaccharide), â€”CO(OCH2CH2)nOH, â€”CO(OCH2CH2)nOCH3, â€”CO(OCH2CH2)nOCH2CH3, â€”CH2OH, â€”CH2OSO3H, â€”CH2OPO3H2, â€”CH2O(C6H5), â€”CH2O(C1-C20 straight or branched chain alkyl), â€”CH2O(C2-C20 straight or branched chain alkenyl), â€”CH2O(C2-C20 straight or branched chain alkynyl), â€”CH2O2C(C1-C20 straight or branched chain alkyl), â€”CH2O2C(C2-C20 straight or branched chain alkenyl), â€”CH2O2C(C2-C20 straight or branched chain alkynyl), â€”CH2O(myo-inosityl), â€”CH2O(scyllo-inosityl), â€”CH2O(cyclitol), â€”CH2O(conduritol A), â€”CH2O(quebrachitol), â€”CH2O(monosaccharide), â€”CH2O(disaccharide), â€”CH2O(oligosaccharide), â€”CH2(OCH2CH2)nOH, â€”CH2(OCH2CH2)nOCH3, â€”CH2(OCH2CH2)nOCH2CH3, â€”CH2O2C(OCH2CH2)nOH, â€”CH2O2C(OCH2CH2)nOCH3, and â€”CH2O2C(OCH2CH2)nOCH2CH3; the myo-inosityl, scyllo-inosityl, cyclitol, conduritol A, quebrachitol, monosaccharide, disaccharide, oligosaccharide, â€”CH2(OCH2CH2)nOH and â€”CH2O2C(OCH2CH2)nOH being optionally substituted with one or more â€”C(O)C1-C20 straight or branched chain alkyl, â€”C(O)C2-C20 straight or branched chain alkenyl, â€”C(O)C2-C20 straight or branched chain alkynyl, sulfate, or mono-, di- or tri-phosphate groups; R3 is selected from the group consisting of â€”C(CH3)(&boxH;CH2) and â€”CH(CH3)2; each n is independently an integer from 1 to 20; D-enantiomers, L-enantiomers, and racemates thereof; and pharmaceutically acceptable salts thereof;with the proviso that the compound of formula I is not:3&bgr;-3-hydroxylup-20(29)-en-28-oic acid (â€œbetulinic acidâ€ ); 3&bgr;-lup-20(29)-ene-3,28-diol (â€œbetulinâ€ ); 3&bgr;-lup-20(29)-ene-3,28-diol diacetate (â€œ3,28-diacetylbetulinâ€ ); 3&bgr;-3-(acetyloxy)lup-20(29)-en-28-oic acid (â€œ3-acetylbetulinic acidâ€ ); 3&bgr;-3-(1-oxobutoxy)lup-20(29)-en-28-oic acid (â€œ3-butyrylbetulinic acidâ€ ); 3&bgr;-3-(2,3-dihydroxycinnamoyl)lup-20(29)-en-28-oic acid (â€œ3-(2,3-dihydroxycinnamoyl)betulinic acidâ€ ); 3&bgr;-lup-20(29)-ene-3,28-diol 3-acetate (â€œ3-acetylbetulinâ€ ); 3&bgr;-lup-20(29)-ene-3,28-diol 28-acetate (â€œ28-acetylbetulinâ€ ); 3&bgr;-3-hydroxylup-20(29)-en-28-oic acid methyl ester (â€œmethyl betulinateâ€ ); 3&bgr;-3-(acetyloxy)lup-20(29)-en-28-oic acid methyl ester (â€œmethyl 3-acetylbetulinateâ€ ); 3&bgr;-3-hydroxylup-20(29)-en-28-oic acid ethyl ester (â€œethyl betulinateâ€ ); 3&bgr;-3-hydroxylup-20(29)-en-28-oic acid butyl ester (â€œbutyl betulinateâ€ ); 3&bgr;-lupane-3,28-diol (â€œdihydrobetulinâ€ ); 3&bgr;-3-hydroxylupan-28-oic acid (â€œdihydrobetulinic acidâ€ ); 3&bgr;-3-hydroxylupan-28-oic acid methyl ester (â€œmethyl dihydrobetulinateâ€ ); 3&bgr;-3-(acetyloxy)lupan-28-oic acid methyl ester (â€œmethyl 3-acetyldihydrobetulinateâ€ ); 3&bgr;-3-(acetyloxy)-lupan-28-oic acid (â€œ3-acetyldihydrobetulinic acidâ€ ); 3&bgr;-lupan-3,28-diol diacetate (â€œ3,28-diacetyldihydrobetulinâ€ ); 3&bgr;-lupane-3,28-diol dibutanoate (â€œ3,28-dibutyryldihydrobetulinâ€ ); 3&bgr;-3-(3-methyl-1-oxobutoxy)lupan-28-oic acid (â€œ3-(3-methylbutryryl)dihydrobetulinic acidâ€ ); 3&bgr;-3-((1-oxo-2-butenyl)oxy)lup-20(29)-en-28-oic acid (â€œ3-(trans-2-butenyl)betulinic acidâ€ ); 3&bgr;-3-(2,2-dimethyl-1-oxopropoxy)lupan-28-oic acid (â€œ3-(2,2-dimethylpropionyl)dihydrobetulinic acidâ€ ); 3&agr;-28-hydroxylup-20(29)-en-3-yl-6-O-(6-deoxy-&agr;-L-mannopyranosyl)-&bgr;-D-glucopyranoside; 3&agr;-28-hydroxylup-20(29)-en-3-yl-&bgr;-D-glucopyranoside; 3&agr;,4&agr;-3-(&bgr;-D-glucopyranosyloxy)lup-20(29)-en-28-oic acid; 3-(&bgr;-D-glucopyranosyloxy)lup-20(29)-en-28-oic acid; 3&bgr;-28-hydroxylup-20(29)-en-3-yl-&bgr;-D-glucopyranoside; 3&bgr;-3-hydroxylup-20(29)-en-28-yl-&bgr;-D-glucopyranoside; 3&bgr;-28(acetyloxy)lup-20(29)-en-3-yl-2-deoxy-&agr;-D-arabinohexopyranoside triacetate; 3&bgr;-28(acetyloxy)lup-20(29)-en-3-yl-2-deoxy-&bgr;-L-arabinohexopyranoside triacetate; 3&bgr;-28(acetyloxy)lup-20(29)-en-3-yl-2,6-dideoxy-&bgr;-L-arabinohexopyranoside diacetate; 3&bgr;-3-(acetyloxy)lup-20(29)-en-28-yl-2-deoxy-&agr;-D-arabinohexopyranoside triacetate; 3&bgr;-3-(acetyloxy)lup-20(29)-en-28-yl-2,6-dideoxy-&bgr;-L-arabinohexopyranoside diacetate; 3&bgr;-28-hydroxylup-20(29)-en-3-yl-2-deoxy-&agr;-D-arabinohexopyranoside; 3&bgr;-28-hydroxylup-20(29)-en-3-yl-2-deoxy-&bgr;-L-arabinohexopyranoside; 3&bgr;-28-hydroxylup-20(29)-en-3-yl-2,6-dideoxy-&bgr;-L-arabinohexopyranoside; 3&bgr;-3-hydroxylup-20(29)-en-28-yl-2-deoxy-&agr;-D-arabinohexopyranoside; 3&bgr;-lup-20(29)-en-3,28-diyl-bis-&bgr;-D-glucopyranoside; 3&bgr;-lup-20(29)-en-3,28-diyl-bis-4-O-&agr;-D-glucopyranosyl-&bgr;-D-glucopyranoside; 3&bgr;-lup-20(29)-en-3,28-diyl-bis-(4-O-(2,3,4,6-tetra-O-acetyl-&agr;-D-glucopyranosyl)-&bgr;-D-glucopyranoside hexaacetate; 3&bgr;-3-((4-O-&agr;-D-glucopyranosyl-&bgr;-D-glucopyranosyl)oxy)lup-20(29)-en-28-oic acid; 3&bgr;-3-((6-O-&bgr;-D-glucopyranosyl-&bgr;-D-glucopyranosyl)oxy)lup-20(29)-en-28-oic acid; 3&bgr;-3-hydroxylup-20(29)-en-28-yl-2,6-dideoxy-&bgr;-L-arabinohexopyranoside; 3&bgr;-3-((2-O-&agr;-L-arabinopyranosyl-6-deoxy-&bgr;-D-glucopyranosyl)oxy)lup-20(29)-en-28-oic acid; 3&bgr;-3-((2-O-&bgr;-D-glucopyranosyl-&bgr;-D-glucopyranosyl)oxy)lup-20(29)-en-28-oic acid; 3&bgr;-3-hydroxylup-20(29)-en-28-oic acid 2,3,4,6-tetra-O-acetyl-&bgr;-D-glucopyranosyl ester; 3&bgr;-3-hydroxylup-20(29)-en-28-oic acid &bgr;-D-galactopyranosyl ester; 3&bgr;-hydroxylup-20(29)-en-28-oic acid 4O-&bgr;-D-galactopyranosyl-&bgr;-D-glucopyranosyl ester; 3&bgr;-3-((2,3,4,6-tetra-O-acetyl-&bgr;-D-glucopyranosyl)oxy)lup-20(29)-en-28-oic acid methyl ester; 3&bgr;-3-(acetyloxy)lup-20(29)-en-28-oic acid 2,3,4,6-tetra-O-acetyl-&bgr;-D-glucopyranosyl ester; 3&bgr;-3-(acetyloxy)lup-20(29)-en-28-oic acid &bgr;-D-glucopyranosyl ester; 3&bgr;-3-((2,3,4,6-tetra-O-acetyl-&bgr;-D-glucopyranosyl)oxy)lup-20(29)-en-28-oic acid 2,3,4,6-tetra-O-acetyl-&bgr;-D-glucopyranosyl ester; 3&bgr;-3-((2,3,4,6-tetra-O-acetyl-&bgr;-D-glucopyranosyl)oxy)lupan-28-oic acid methyl ester; 3&bgr;-3-(acetyloxy)lupan-28-oic acid 2,3,4,6-tetra-O-acetyl-&bgr;-D-glucopyranosyl ester; 3&agr;-3-((2,3,4,6-tetra-O-acetyl-&bgr;-D-glucopyranosyl)oxy)lup-20(29)-en-28-oic acid; 3&bgr;-3-((2,3,4,6-tetra-O-acetyl-&bgr;-D-glucopyranosyl)oxy)lup-20(29)-en-28-oic acid; 3&bgr;-3-(acetyloxy)lupan-28-oic acid &bgr;-D-glucopyranosyl ester; 3&bgr;-3-hydroxylup-20(29)-en-28-oic acid &bgr;-D-glucopyranosyl ester; 3&bgr;-3-hydroxylup-20(29)-en-28-oic acid &bgr;-D-xylopyranosyl ester; 3&bgr;-hydroxylup-20(29)-en-28-oic acid &bgr;-D-glucopyranosyl ester 2â€²,3â€²,4â€²,6â€²-tetrabenzoate; 3&bgr;-lup-20(29)-en-28-oic acid (&bgr;-D-glucopyranosyloxy)-&bgr;-D-glucopyranosyl ester octabenzoate; 3&bgr;-lup-20(29)-en-28-oic acid (&agr;-L-arabinopyranosyloxy)-&agr;-L-arabinopyranosyl ester; 3&bgr;-lup-20(29)-en-28-oic acid (&agr;-L-arabinopyranosyloxy)-&agr;-L-arabinopyranosyl ester hexabenzoate; 3&bgr;-3-(&bgr;-D-glucopyranosyloxy)lup-20(29)-en-28-oic acid methyl ester; 3&bgr;-3-(&bgr;-D-glucopyranosyloxy)lupan-28-oic acid methyl ester; 3&bgr;-3-hydroxylupan-28-oic acid &bgr;-D-glucopyranosyl ester; 3&bgr;-17-carboxy-28-norlup-20(29)-en-3-yl-3-O-&bgr;-D-xylopyranosyl-&bgr;-D-glucopyranosiduronic acid; 3&bgr;-17-carboxy-28-norlup-20(29)-en-3-yl-2-O-&bgr;-D-xylopyranosyl-&bgr;-D-glucopyranosiduronic acid; 3&bgr;-3-(&bgr;-D-glucopyranosyloxy)lup-20(29)-en-28-oic acid 6-O-&bgr;-D-glucopyranosyl-&bgr;-D-glucopyranosyl ester; 3&agr;-3-hydroxylup-20(29)-en-28-oic acid O-6-deoxy-&agr;-L-mannopyranosyl-(1â†’4)-O-&bgr;-D-glucopyranosyl-(1â†’6)-O-&bgr;-D-glucopyranosyl ester; 3&agr;-3-(&bgr;-D-glucopyranosyloxy)lup-20(29)-en-28-oic acid O-6-deoxy-&agr;-L-mannopyranosyl-(1â†’4)-O-&bgr;-D-glucopyranosyl-(1â†’6)-O-&bgr;-D-glucopyranosyl ester; 3&bgr;-3-(&bgr;-D-glucopyranosyloxy)lup-20(29)-en-28-oic acid O-6-deoxy-&agr;-L-mannopyranosyl-(1â†’4)-O-&bgr;-D-glucopyranosyl-(1â†’6)-O-&bgr;-D-glucopyranosyl ester; 3&bgr;-28-methoxy-28-oxolup-20(29)-en-3-yl-O-2,3,4-tri-O-acetyl-6-deoxy-&agr;-L-mannopyranosyl-(1â†’2)-O-3,4,6-tri-O-acetyl-&bgr;-D-glucopyranosyl-(1â†’2)-&bgr;-D-glucopyranosiduronic acid methyl ester diacetate; 3&bgr;-17-carboxy-28-norlup-20(29)-en-3-yl-O-6-deoxy-&agr;-L-mannopyranosyl-(1â†’2)-O-&bgr;-D-glucopyranosyl-(1â†’2)-&bgr;-D-glucopyranosiduronic acid; 3&bgr;-17-carboxy-28-norlup-20(29)-en-3-yl-O-6-deoxy-&agr;-L-mannopyranosyl-(1â†’2)-O-&bgr;-D-xylopyranosyl-(1â†’2)-&bgr;-D-glucopyranosiduronic acid; 3&bgr;-17-carboxy-28-norlup-20(29)-en-3-yl-O-2,3,4-tri-O-acetyl-6-deoxy-&agr;-L-mannopyranosyl-(1â†’2)-O-3,4,6-tri-O-acetyl-&bgr;-D-glucopyranosyl-(1â†’2)-&bgr;-D-glucopyranosiduronic acid diacetate; 3&bgr;-17-carboxy-28-norlup-20(29)-en-3-yl-O-2,3,4-tri-O-acetyl-6-deoxy-&agr;-L-mannopyranosyl-(1â†’2)-O-3,4-di-O-acetyl-&bgr;-D-xylopyranosyl-(1â†’2)-&bgr;-D-glucopyranosiduronic acid diacetate; 3&bgr;-28-methoxy-28-oxolup-20(29)-en-3-yl-O-2,3,4-tri-O-acetyl-6-deoxy-&agr;-L-mannopyranosyl-(1â†’2)-O-3,4,6-tri-O-acetyl-&bgr;-D-glucopyranosyl-(1â†’2)-&bgr;-D-glucopyranosiduronic acid methyl ester diacetate; 3&bgr;-28-methoxy-28-oxolup-20(29)-en-3-yl-O-2,3,4-tri-O-acetyl-6-deoxy-&agr;-L-mannopyranosyl-(1â†’2)-O-3,4-di-O-acetyl-&bgr;-D-xylopyranosyl-(1â†’2)-&bgr;-D-glucopyranosiduronic acid methyl ester diacetate; 3&bgr;-3-((O-&agr;-L-arabinofuranosyl-(1â†’2)-O-6-deoxy-&agr;-L-mannopyranosyl-(1â†’4)-&bgr;-D-glucopyranosyl)oxy)-lup-20(29)-en-28-oic acid; 3&bgr;-3-((O-&agr;-L-arabinofuranosyl-(1â†’2)-O-6-deoxy-&agr;-L-mannopyranosyl-(1â†’4)-&bgr;-D-glucopyranosyl)oxy)-lup-20(29)-en-28-oic acid methyl ester; 3&bgr;-28-hydroxylup-20(29)-en-3-yl-4-O-&bgr;-D-glucopyranosyl-&bgr;-D-glucopyranoside; 3&bgr;-28-hydroxylup-20(29)-en-3-yl-4-O-&agr;-D-glucopyranosyl-&bgr;-D-glucopyranoside; 3&bgr;-3-hydroxylup-20(29)-en-28-yl-4-O-&agr;-D-glucopyranosyl-&bgr;-D-glucopyranoside; 3&bgr;-28-hydroxylup-20(29)-en-3-yl-&bgr;-D-xylopyranoside; 3-(&bgr;-D-glucopyranosyloxy)lup-20(29)-en-28-oic acid O-6-deoxy-&agr;-L-mannopyranosyl-(1â†’4)-O-&bgr;-D-glucopyranosyl-(1â†’6)-O-&bgr;-D-glucopyranosyl ester; 3&agr;-lup-20(29)-en-28-oic acid 3-(&bgr;-D-glucopyranosyloxy)-O-6-deoxy-&agr;-L-mannopyranosyl-(1â†’4)-O-&bgr;-D-glucopyranosyl-(1â†’6)-O-&bgr;-D-glucopyranosyl ester; 3&agr;,4-&agr;-3-(&bgr;-D-glucopyranosyloxy)lup-20(29)-en-28-oic acid; 3&agr;-lup-20(29)-en-28-oic acid 3-((O-6-acetyl-&bgr;-D-glucopyranosyl)oxy)-O-6-deoxy-&agr;-L-mannopyranosyl-(1â†’4)-O-&bgr;-D-glucopyranosyl-(1â†’6)-O-&bgr;-D-glucopyranosyl ester; 3&bgr;-28-hydroxylup-20(29)-en-3-yl-O-&agr;-D-glucopyranosyl-(1â†’4)-O-&agr;-D-glucopyranosyl-(1â†’4)-O-&bgr;D-glucopyranosyl-(1â†’4)-&bgr;-D-glucopyranoside; 3&agr;-3-(sulfooxy)lup-20(29)-en-28-oic acid 28-O-6-deoxy-&agr;-L-mannopyranosyl-(1â†’4)-O-&agr;-D-glucopyranosyl-(1â†’6)-&bgr;-D-glucopyranosyl ester; 3-(sulfooxy)lup-20(29)-en-28-oic acid 28-(O-2,3,4-tri-O-acetyl-6-deoxy-&agr;-L-mannopyranosyl-(1â†’4)-O-2,3,6-tri-O-acetyl-&bgr;-D-glucopyranosyl-(1â†’6)-2,3,4-tri-O-acetyl-&bgr;-D-glucopyranosyl) ester; 3&agr;-3-(acetyloxy)lup-20(29)-en-28-oic acid O-2,3,4-tri-O-acetyl-6-deoxy-&agr;-L-mannopyranosyl-(1â†’4)-O-2,3,6-tri-O-acetyl-&bgr;-D-glucopyranosyl-(1â†’6)-2,3,4-tri-O-acetyl-&bgr;-D-glucopyranosyl) ester; 28-(acetyloxy)lup-20(29)-en-3-yl-4-O-(2,3,4,6-teta-O-acetyl-&agr;-D-glucopyranosyl)-&bgr;-D-glucopyranoside triacetate; 3&bgr;-28-(acetyloxy)lup-20(29)-en-3-yl-4-O-(2,3,4,6-tetra-O-acetyl-&bgr;-D-glucopyranosyl)-&bgr;-D-glucopyranoside triacetate; 3&bgr;-3-(acetyloxy)lup-20(29)-en-28-yl-4-O-(2,3,4,6-tetra-O-acetyl-&agr;-D-glucopyranosyl)-&bgr;-D-glucopyranoside triacetate; 3&bgr;-3-((2,3,4,6-tetra-O-acetyl-&bgr;D-glucopyranosyl)oxy)lup-20(29)-en-28-yl-&bgr;-D-glucopyranoside tetraacetate; 3&bgr;-28-(acetyloxy)lup-20(29)-en-3-yl-&bgr;-D-glucopyranoside tetraacetate; 3&bgr;-3-(acetyloxy)lup-20(29)-en-28-yl-&bgr;-D-glucopyranoside tetraacetate; 3&bgr;-lup-20(29)-en-3-yl-&bgr;-D-glucopyranoside tetraacetate; 3&bgr;-lup-20(29)-en-3-yl-6-deoxy-&agr;-L-mannopyranoside; 3&bgr;-3-((6-deoxy-2-O-&bgr;-D-glucopyranosyl-&agr;-L-mannopyranosyl)oxy)lup-20(29)-en-28-oic acid; 3&bgr;-3-((6-deoxy-&agr;-L-mannopyranosyl)oxy)lup-20(29)-en-28-oic acid; 3&bgr;-lup-20(29)-en-3-yl-4-O-&bgr;-D-xylopyranosyl-&bgr;-D-glucopyranoside; 3&bgr;-28-(acetyloxy)lup-20(29)-en-3-yl-&agr;-D-glucopyranoside tetraacetate; 3&bgr;-3-hydroxylup-20(29)-en-28-yl-&bgr;-D-glucopyranoside 2,3,4,6-tetraacetate; 3&bgr;-28-((6-O-D-apio-&bgr;-D-furanosyl-&bgr;-D-glucopyranosyl)oxy)-28-oxolup-20(29)-en-3-yl-4-O-&bgr;-D-galactopyranosyl-&bgr;-D-glucopyranosiduronic acid; 3&bgr;-3-((2-propenyl)oxy)lup-20(29)-en-28-oic acid (â€œ3-O-allylbetulinic acidâ€ ); 3&bgr;-3,28-dimethoxylup-20(29)-ene (â€œ3,28-di-O-methylbetulinâ€ ); 3&bgr;-3,28-dimethoxylupane (â€œ3,28-di-O-methyldihydrobetulinâ€ ); 3&bgr;-28-methoxylupan-3-ol (â€œ28-methyldihydrobetulinâ€ ); 3&bgr;-3-methoxylup-20(29)-en-28-oic acid (â€œ3-O-methylbetulinic acidâ€ ); 3&bgr;-3-methoxylup-20(29)-en-28-oic acid methyl ester (â€œmethyl 3-O-methylbetulinateâ€ ); 8&xgr;-2,6-anhydro-9-O-((3&bgr;,18&bgr;)-17-carboxy-28-norlupan-3-yl)-1,7,8-trideoxy-8-methyl-3,4,5-tris-O-(phenylmethyl)-L-glycero-D-galactononitol; 2,6-anhydro-9-O-((3&bgr;,18&bgr;)-17-carboxy-28-norlup-20(29)-en-3-yl)-1,7,8-trideoxy-8-methylene-3,4,5-tris-O-(phenylmethyl)-L-glycero-D-galactononitol; 3&agr;-3-methoxylup-20(29)-en-28-oic acid; or 3&agr;-3-methoxylup-20(29)-en-28-oic acid methyl ester.