Cell division inhibitor and a production method thereof
The present invention relates to a cell division inhibitor comprising various dehydrodiketopiperazines such as dehydrophenylahistin, or analogs thereof as an active ingredient, and a dehydrogenase and a method for producing the same inhibitor.
1 - 14 . (canceled)
15 . A compound of formula (I) or pharmaceutically acceptable salt thereof:
wherein:
each of X 1 and X 2 is independently oxygen or sulfur;
Y 3 is oxygen, sulfur, —NR 3 —, or —CR 31 R 32 —;
Y 4 is oxygen, sulfur, —NR 4 —, or —CR 41 R 42 —;
R 10 is an aryl or aralkyl and is optionally substituted with other substituent(s) and optionally comprises one or more heteroatoms;
R 20 is an aryl or aralkyl and is optionally substituted with other substituent(s) and optionally comprises one or more heteroatoms, with the proviso that R 20 does not include a phenyl group;
each of R 3 and R 4 is independently selected from the group consisting of hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro, and aryl, each of which is optionally substituted with other substituent(s), wherein any part of a carbon chain in R 3 and R 4 may be branched or cyclized, and may comprise one or more heteroatoms;
each of R 31 , R 32 , R 41 , and R 42 is independently selected from the group consisting of hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro, and aryl, each of which is optionally substituted with other substituent(s), wherein any part of a carbon chain in R 31 , R 32 , R 41 , and R 42 may be branched or cyclized, and may comprise one or more heteroatoms;
R 10 and any of R 3 , R 31 , or R 32 may together from a ring;
R 20 and any of R 4 , R 41 , or R 42 may together from a ring;
each bond depicted by a solid line and dashed line represents a carbon-carbon single bond or a carbon-carbon double bond with E or Z configurations; and
at least one of said groups may have a protecting group capable of decomposing in vivo;
with the proviso that the compound of formula I does not include the compound having the following structure:
16 . The compound of claim 15 , wherein each bond depicted by a solid line and dashed line represents a carbon-carbon double bond.
17 . The compound of claim 16 , wherein each of X 1 and X 2 is oxygen, Y 3 is —NR 3 —, and Y 4 is —NR 4 —.
18 . The compound of claim 17 , wherein each of Y 3 and Y 4 is —NH—.
19 . The compound of claim 15 , wherein at least one of R 10 and R 20 is substituted with 1,1-dimethyl-2-propenyl.
20 . The compound of claim 15 , wherein at least one of R 10 and R 20 has the following structure:
and is optionally substituted with other substituent(s).
21 . The compound of claim 15 , wherein:
R 10 is a phenyl or phenylalkyl and is optionally substituted with other substituent(s); and
R 20 is an imidazolyl or imidazolylalkyl and is optionally substituted with other substituent(s).
22 . The compound of claim 15 selected from the group consisting of:
3-(imidazole-4-ylmethylene)-6-(phenylmethylene)piperazine-2,5-dione;
3-[(5-methylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione;
3-[(5-ethylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione;
3-[(5-butylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione;
3-[(5-pentylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione; and
3-{[5-(1, 1-dimethyl-2-propenyl)imidazole-4-yl]methylene}-6-(phenylmethylene) piperazine-2,5-dione.
23 . A method of inhibiting cell division in a subject, comprising administering to the subject a compound of claim 15 .
24 . The method of claim 23 , wherein the compound is selected from the group consisting of:
3-(imidazole-4-ylmethylene)-6-(phenylmethylene)piperazine-2,5-dione;
3-[(5-methylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione;
3-[(5-ethylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione;
3-[(5-butylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione; and
3-[(5-pentylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione.
25 . The method of claim 23 , wherein the compound is 3-{[5-(1,1-dimethyl-2-propenyl)imidazole-4-yl]methylene}-6-(phenylmethylene)piperazine-2,5-dione.
26 . A method of treating a subject having a tumor, comprising administering to the subject a compound of claim 15 .
27 . The method of claim 26 , wherein the compound is selected from the group consisting of:
3-(imidazole-4-ylmethylene)-6-(phenylmethylene)piperazine-2,5-dione;
3-[(5-methylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione;
3-[(5-ethylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione;
3-[(5-butylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione; and
3-[(5-pentylimidazole-4-yl)methylene]-6-(phenylmethylene)piperazine-2,5-dione.
28 . The method of claim 26 , wherein the compound is 3-{[5-(1,1-dimethyl-2-propenyl)imidazole-4-yl]methylene}-6-(phenylmethylene)piperazine-2,5-dione.