Compound of a reverse-turn mimetic and a production method and use therefor
This invention relates to novel compounds of reverse-turn mimetics, having pyrazino-triazinone as a basic framework, and a method of preparing the same, and the use thereof to treat diseases such as cancer, in particular, acute myeloid leukemia.
1. A compound represented by Formula I below or a pharmaceutically acceptable salt thereof:
wherein R a is C 1 -C 6 alkyl group, C 2 -C 6 alkenyl group, or C 2 -C 6 alkynyl group;
wherein R 1 is H, C 1 -C 12 alkyl group or substituted C 1 -C 12 alkyl group;
R 2 is H, C 1 -C 30 alkyl group, C 3 -C 10 cycloalkyl group, amino group, C 1 -C 30 alkoxy group, benzyl group,
and wherein the C 1 -C 30 alkyl group, the C 3 -C 10 cycloalkyl group, the amino group, the C 1 -C 30 alkoxy group, and the benzyl group may be substituted with at least one Rq,
R 1 and R 2 may be joined together to form an aliphatic ring, an aliphatic hetero ring, an aromatic ring, or an aromatic hetero ring or to form a spiro bond, in which the rings may optionally have at least one substituent;
R 3 is C 3 -C 20 acyl group, substituted C 3 -C 20 acyl group, cyano group or sulfonyl group;
R 4 is H, substituted or unsubstituted amino group, C 1 -C 20 acyl group or substituted C 1 -C 20 acyl group; and
R p is H or a prodrug functional group, wherein the prodrug functional group is —PO 3 H 2 , —HPO 3 − Na + , —PO 3 2− Na 2 + , —PO 3 2− K 2 + , —PO 3 2− Mg 2+ , PO 3 2− Ca 2+ ,
wherein Rq is H, at least one C 1 -C 10 alkyl, substituted C 1 -C 10 alkyl, C 1 -C 10 cycloalkyl, substituted C 1 -C 10 cycloalky, amino, substituted amino, C 1 -C 10 alkoxy, substituted C 1 -C 10 alkoxy, halogen, —OH, benzyl, substituted benzyl, acyl, substituted acyl, phenyl, substituted phenyl, butyl oxy carbonyl (BOC),
wherein X is H, at least one C 1 -C 10 alkyl, substituted C 1 -C 10 alkyl, acyl, C 3 -C 10 cycloalkyl, C 1 -C 10 alkoxy, phenyl, substituted phenyl, benzyl, substituted benzyl, a C 1 -C 10 hetero aromatic ring, C 3 -C 10 heterocycloalkyl, substituted C 3 -C 10 heterocycloalkyl, amino, substituted amino, or —OH,
wherein the C 3 -C 10 heterocycloalkyl and the substituted C 3 -C 10 heterocycloalkyl contain one or two heteroatoms wherein each heteroatom is independently selected from N and O, and wherein the substituted C 3 -C 10 heterocycloalkyl is methyl substituted C 3 -C 10 heterocycloalkyl, methoxy substituted C 3 -C 10 heterocycloalkyl, or
substituted C 3 -C 10 heterocycloalkyl.
2. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R a is C 1 -C 6 alkyl group or C 2 -C 6 alkenyl group; and R p is H.
3. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R a is a methyl group.
4. The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein R b is selected from the group consisting of
5. The compound or pharmaceutically acceptable salt thereof of claim 1 ,
wherein R 1 is H or C 1 -C 5 alkyl group, and the C 1 -C 5 alkyl group may be substituted with at least one Rq;
R 2 is H, C 1 -C 10 alkyl group, C 3 -C 10 cycloalkyl group, amino group, C 1 -C 10 alkoxy group, benzyl group,
and the C 1 -C 10 alkyl group, the C 3 -C 10 cycloalkyl group, the amino group, the C 1 -C 10 alkoxy group, and the benzyl group may be substituted with at least one Rq,
R 1 and R 2 may be fused with N, thus forming any one ring selected from the group consisting of
R 3 is
and
R 4 is H, amino group substituted with at least one Rq,
wherein Rq is H, at least one C 1 -C 10 alkyl, substituted C 1 -C 10 alkyl, C 1 -C 10 cycloalkyl, substituted C 1 -C 10 cycloalkyl, amino, substituted amino, C 1 -C 10 alkoxy, substituted C 1 -C 10 alkoxy, halogen, —OH, benzyl, substituted benzyl, acyl, substituted acyl, phenyl, substituted phenyl, butyl oxy carbonyl (BOC),
wherein X is H, at least one C 1 -C 10 alkyl, substituted C 1 -C 10 alkyl, acyl, C 3 -C 10 cycloalkyl, C 1 -C 10 alkoxy, phenyl, substituted phenyl, benzyl, substituted benzyl, a C 1 -C 10 hetero aromatic ring, C 3 -C 10 heterocycloalkyl, substituted C 3 -C 10 heterocycloalkyl, amino, substituted amino, or —OH,
wherein the C 3 -C 10 heterocycloalkyl and the substituted C 3 -C 10 heterocycloalkyl contain one or two heteroatoms wherein each heteroatom is independently selected from N and O, wherein the substituted C 3 -C 10 heterocycloalkyl is methyl substituted C 3 -C 10 heterocycloalkyl, methoxy substituted C 3 -C 10 heterocycloalkyl, or
substituted C 3 -C 10 heterocycloalkyl.
6. The compound or pharmaceutically acceptable salt thereof of claim 1 , which is a compound (Compound E-5) represented by
7. A method of treating cancer comprising administering to a subject in need thereof a pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the cancer is acute myeloid leukemia.
8. A method of treating cancer comprising administering to a subject in need thereof an injectable pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the cancer is acute myeloid leukemia.