Derivative of β-apopicropodophyllin and method of preparing thereof
Provided are a novel derivative of β-apopicropodophyllin and a method of preparing the same, and more particularly, a compound represented by Formula 1 below, which is a novel derivative of β-apopicropodophyllin derived from podophyllotoxin, which is an anticancer agent, a method of preparing the same, and a composition for treating cancer, which includes the compound. In Formula 1, R is a C 2 to C 10 alkyl group, a C 2 to C 10 alkyl group containing an allyl- or alkyne, a —[CH 2 ] n —C 3 to C 8 cycloalkyl group, a substituted or unsubstituted —[CH 2 ] n -phenyl group, a substituted or unsubstituted —[CH 2 ] n —C 5 to C 6 heteroaromatic group, a —C(═O)—C 1 to C 8 alkyl group, a substituted or unsubstituted —C(═O)—[CH 2 ] n -phenyl group, or a substituted or unsubstituted —C(═O)—[CH 2 ] n —C 5 to C 6 heteroaromatic group, wherein n is an integer of 0 to 6.
1. A compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof:
In Formula 1, R is a C 2 to C 10 alkyl group containing an allyl- or alkyne, a —[CH 2 ] n —C 3 to C 8 cycloalkyl group, a substituted or unsubstituted —[CH 2 ] n -phenyl group, a substituted or unsubstituted —[CH 2 ] n —C 5 to C 6 heteroaromatic group, a —C(═O)—C 1 to C 8 alkyl group, a substituted or unsubstituted —C(═O)—[CH 2 ] n -phenyl group, or a substituted or unsubstituted —C(═O)—[CH 2 ] n —C 5 to C 6 heteroaromatic group, wherein n is an integer of 0 to 6.
2. The compound of claim 1 , wherein the compound is selected from the group consisting of:
acetic acid (5S)-2,6-dimethoxy-4-(6-oxo-5,6,8,9-tetrahydrofuro[3′,4′:6,7]naphtho[2,3-d] [1,3]dioxol-5-yl)-phenyl ester;
benzoic acid (5S)-2,6-dimethoxy-4-(6-oxo-5,6,8,9-tetrahydrofuro[3′,4′:6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-phenyl ester;
propionic acid (5S)-2,6-dimethoxy-4-(6-oxo-5,6,8,9-tetrahydrofuro[3′,4′:6,7]naphtho [2,3-d] [1,3]dioxol-5-yl)-phenyl ester;
nicotinic acid (5S)-2,6-dimethoxy-4-(6-oxo-5,6,8,9-tetrahydrofuro[3′,4′:6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-phenyl ester;
1 H-pyrrole-2-carboxylic acid (5S)-2,6-dimethoxy-4-(6-oxo-5,6,8,9-tetrahydrofuro [3′,4′:6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-phenyl ester;
3H-imidazole-4-carboxylic acid (5S)-2,6-dimethoxy-4-(6-oxo-5,6,8,9-tetrahydrofuro [3′,4′:6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-phenyl ester;
(5S)-5-(4-but-3-enyloxy-3,5-dimethoxy-phenyl)-5,9-dihydro-8H-furo[3′,4′:6,7]naphtho [2,3-d][1,3]dioxol-6-one;
(5S)-5-(4-cyclohexylmethoxy-3,5-dimethoxy-phenyl)-5,9-dihydro-8H-furo[3′,4′:6,7] naphtho [2,3-d][1,3]dioxol-6-one;
(5S)-5-(4-cyclopentylmethoxy-3,5-dimethoxy-phenyl)-5,9-dihydro-8H-furo[3′,4′:6,7] naphtho[2,3-d][1,3]dioxol-6-one;
(5S)-5-[4-(2-cyclohexyl-ethoxy)-3,5-dimethoxy-phenyl]-5,9-dihydro-8 H-furo[3′,4′:6,7] naphtho[2,3-d][1,3]dioxol-6-one;
(5S)-5-[3,5-dimethoxy-4-(pyridin-4-ylmethoxy)-phenyl]-5,9-dihydro-8H-furo[3′,4′:6,7] naphtho[2,3-d][1,3]dioxol-6-one;
(5S)-5-(4-benzyloxy-3,5-dimethoxy-phenyl)-5,9-dihydro-8H-furo[3′,4′:6,7]naphtho[2,3-d][1,3]dioxol-6-one;
(5S)-5-[3,5-dimethoxy-4-(4-trifluoromethyl-benzyloxy)-phenyl]-5,9-dihydro-8H-furo [3′,4′:6,7]naphtho[2,3-d][1,3]dioxol-6-one;
(5S)-5-[3,5-dimethoxy-4-(4-methyl-benzyloxy)-phenyl]-5,9-dihydro-8H-furo[3′,4′:6,7] naphtho[2,3-d][1,3]dioxol-6-one; and
(5S)-5-[3,5-dimethoxy-4-(4-fluorobenzyloxy)-phenyl]-5,9-dihydro-8H-furo[3′,4′:6,7] naphtho[2,3-d][1,3]dioxol-6-one.
3. A pharmaceutical composition for treating cancer, comprising the compound represented by Formula 1 of claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient.