Terpenoid derivatives, pharmaceutical preparations containing these derivatives and their use in neuroprotection

A method of treatment of neurodegenerative disease, comprising the step of administering at least one terpenoid derivative of the general formula Ia,

• wherein,
• is single or double bond;
• X is independently selected from —CH2O—, —C(O)NH—, —C(O)O—
• A, B, and Y are independently on each occurrence selected from the group consisting of CH, C, N, NH, O, S;
• m=1, 2, 3;
• R1 is independently selected from H—, CH3(CH2)nCO— or HOOC(CH2)nCO— and n=0-5;
• R2 is independently selected from —CH2OH, —CH2O(CH2)nCH3, —CH2OC(O)(CH2)nCH3, —COOH, —COO(CH2)nCH3 and COO(CH2)Ph, wherein n=0-5;
• R3 is independently selected on each occurrence from C6-C12 aryl;
• heteroaryl containing 5-8 atoms in the aromatic ring of that at least one is heteroatom selected from N, O, S;
• glucose, galactose, mannose, rhamnose, lactose, ribose, arabinose, 2-deoxyglucose, 2-deoxygalactose, 2-deoxymannose, and their peracetylated derivatives;
• while R3 is not present when Y is O or S;
• provided that if X is C(O)NH or C(O)O, R1 is CH3CO—, R2 is —CH2OC(O)CH3 or COOH, A=B=C=N and m=1;
• then R3 is not phenyl, 4-aminophenyl, 4-thiocyanatophenyl, 2-carboxyphenyl, peracetylglucosyl, peracetylgalactosyl;
• or
• X is —CH2NH—,
• A, B, and Y are independently on each occurrence selected from the group consisting of CH, C, N, NH, O, S;
• m=1, 2, 3;
• R1 is independently selected from H—, CH3(CH2)nCO— or HOOC(CH2)nCO— and n=0-5;
• R2 is independently selected from —CH2OH, —CH2O(CH2)nCH3, —CH2OC(O)(CH2)nCH3, —COOH, —COO(CH2)nCH3 and COO(CH2)Ph, wherein n=0-5;
• R3 is independently selected on each occurrence from heteroaryl containing 5-8 atoms in the aromatic ring of that at least one is heteroatom selected from N, O, S;
• glucose, galactose, mannose, rhamnose, lactose, ribose, arabinose, 2-deoxyglucose, 2-deoxygalactose, 2-deoxymannose, and their peracetylated derivatives;
• while R3 is not present when Y is O or S;
• or their pharmaceutically acceptable salts to a subject in need of such treatment.

A method of treatment of neurodegenerative disease, comprising the step of administering at least one terpenoid derivative to a subject in need of such treatment, wherein the at least one terpenoid derivative is selected from the group consisting of 30-1H-1,2,3-triazol-4-yl-methoxylup-20(29)-en-3,28-diol diacetate, 30-(1-methyl1H-1,2,3-triazol-4-yl)-methoxylup-20(29)-en-3,28-diol diacetate, 30-(1-phenyl1H-1,2,3-triazol-4-yl)-methoxylup-20(29)-en-3,28-diol diacetate, 30-(1-[pyridin-2-yl]-1H-1,2,3-triazol-4-yl)-methoxylup-20(29)-en-3,28-diol diacetate, 30-(1-[peracetyl glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methoxylup-20(29)-en-3,28-diol diacetate, 30-(1-[peracetyl galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methoxylup-20(29)-en-3,28-diol diacetate, 30-(1-[glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methoxylup-20(29)-en-3,28-diol diacetate, 30-(1-[galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methoxylup-20(29)-en-3,28-diol diacetate, 30-1H-1,2,3-triazol-4-yl-methoxylup-20(29)-en-3,28-diol, 30-(1-methyl1H-1,2,3-triazol-4-yl)-methoxylup-20(29)-en-3,28-diol, 30-(1-[peracetyl galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methoxylup-20(29)-en-3,28-diol, 30-(1-[galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methoxylup-20(29)-en-3,28-diol, 30-1H-1,2,3-triazol-4-yl-methylaminolup-20(29)-en-3,28-diol diacetate, 30-(1-methyl1H-1,2,3-triazol-4-yl)-methylaminolup-20(29)-en-3,28-diol diacetate, 30-(1-[peracetyl glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methylaminolup-20(29)-en-3,28-diol diacetate, 30-(1-[peracetyl galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methylaminolup-20(29)-en-3,28-diol diacetate, 30-(1-[glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methylaminolup-20(29)-en-3,28-diol diacetate, 30-(1-[galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methylaminolup-20(29)-en-3,28-diol diacetate, 30-1H-1,2,3-triazol-4-yl-methylaminolup-20(29)-en-3,28-diol, 30-(1-methyl1H-1,2,3-triazol-4-yl)-methylaminolup-20(29)-en-3,28-diol, 30-(1-[peracetyl glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methylaminolup-20(29)-en-3,28-diol, 30-(1-[peracetyl galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methylaminolup-20(29)-en-3,28-diol, 30-(1-[glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methylaminolup-20(29)-en-3,28-diol, 30-(1-[galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methylaminolup-20(29)-en-3,28-diol, 30-(1H-1,2,3-triazol-4-yl-methylamino)-3β-hydroxylup-20(29)-en-28-oic acid, 30-[(1-methyl1H-1,2,3-triazol-4-yl)-methylamino]-3β-hydroxylup-20(29)-en-28-oic acid, 30-{(1-[peracetyl glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino}-3β-hydroxylup-20(29)-en-28-oic acid, 30-{(1-[peracetyl galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino}-3β-hydroxylup-20(29)-en-28-oic acid, 30-{(1-[glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino}-3β-hydroxylup-20(29)-en-28-oic acid, 30-{(1-[galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino}-3β-hydroxylup-20(29)-en-28-oic acid, 30-(1H-1,2,3-triazol-4-yl-methylamino)-3β-hydroxylup-20(29)-en-28-oic acid methyl ester, 30-(1H-1,2,3-triazol-4-yl-methoxy)-3β-hydroxylup-20(29)-en-28-oic acid, 30-{(1-[peracetyl galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methoxy}-3β-hydroxylup-20(29)-en-28-oic acid, 30-{(1-[galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methoxy}-3β-hydroxylup-20(29)-en-28-oic acid, 30-(1H-1,2,3-triazol-4-yl-methoxy)-3β-hydroxylup-20(29)-en-28-oic acid methyl ester, 30-{(1-[peracetyl glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methoxy}-3β-hydroxylup-20(29)-en-28-oic acid methyl ester, 30-{(1-[galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methoxy}-3β-hydroxylup-20(29)-en-28-oic acid methyl ester, 30-1H-1,2,3-triazol-4-yl-methylamino,30-oxolup-20(29)-en-3,28-diol diacetate, 30-(1-[peracetyl glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino,30-oxolup-20(29)-en-3,28-diol diacetate, 30-(1-[glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino,30-oxolup-20(29)-en-3,28-diol diacetate, 30-1H-1,2,3-triazol-4-yl-methylamino,30-oxolup-20(29)-en-3,28-diol, 30-(1-[peracetyl glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino,30-oxolup-20(29)-en-3,28-diol, 30-(1-[glucos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino,30-oxolup-20(29)-en-3,28-diol, 30-(1H-1,2,3-triazol-4-yl-methylamino)-3β-hydroxy,30-oxolup-20(29)-en-28-oic acid, 30-{(1-[peracetyl galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino}-3β-hydroxy,30-oxolup-20(29)-en-28-oic acid, 30-{(1-[galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino}-3β-hydroxy,30-oxolup-20(29)-en-28-oic acid, 30-(1H-1,2,3-triazol-4-yl-methylamino)-3β-hydroxy,30-oxolup-20(29)-en-28-oic acid methyl ester, 30-{(1-[peracetyl galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino}-3β-hydroxy,30-oxolup-20(29)-en-28-oic acid methyl ester, and 30-{(1-[galactos-1-yl]-1H-1,2,3-triazol-4-yl)-methylamino}-3β-hydroxy,30-oxolup-20(29)-en-28-oic acid methyl ester, in the form of optically active stereoisomers, racemates, or mixtures thereof, or in the form of pharmaceutically acceptable salts thereof.