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. A cell division inhibitor comprising, as an active ingredient, a compound of formula (II) or an E form thereof, or pharmaceutically acceptable salt thereof:
wherein
R 1 is hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain of R 1 may be branched or cyclized, or may comprise a heteroatom, and further R 1 may be one atom or group, or at most 5 identical or different atoms or groups, and the atoms or groups may mutually form a ring;
R 2 is hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain of R 2 may be branched or cyclized, or may comprise a heteroatom;
each of R 3 and R 4 is independently hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain may be branched or cyclized, or may comprise a heteroatom;
R 5 is hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain of R 5 may be branched or cyclized, or may comprise a heteroatom;
R 6 is hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain of R 6 may be branched or cyclized, or may comprise a heteroatom;
each of R 7 and R 8 is independently hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain may be branched or cyclized, or may comprise a heteroatom;
R 2 and R 3 may form a ring;
R 4 and any of R 5 , R 6 , R 7 and R 8 may form a ring;
the bond depicted by a solid line and dashed line represents a carbon—carbon single bond or a carbon—carbon double bond;
at least one of said groups may have a protecting group capable of decomposing in vivo.
2. The cell division inhibitor according to claim 1 wherein, in said formula (II), the bond depicted by a solid line and dashed line is a carbon—carbon double bond.
3. The cell division inhibitor according to claim 2 wherein, in said formula (II), at least one of R 7 and R 8 is 1,1-dimethyl-2-propenyl.
4. The cell division inhibitor according to claim 1 which is an antitumor agent.
5. A compound of formula (II) or an E form thereof, or pharmaceutically acceptable salt thereof:
wherein
R 1 is hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain of R 1 may be branched or cyclized, or may comprise a heteroatom, and further R 1 may be one atom or group, or at most 5 identical or different atoms or groups, and the atoms or groups may mutually form a ring;
R 2 is hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain of R 2 may be branched or cyclized, or may comprise a heteroatom;
each of R 3 and R 4 is independently hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain may be branched or cyclized, or may comprise a heteroatom;
R 5 is hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain of R 5 may be branched or cyclized, or may comprise a heteroatom;
R 6 is hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain of R 6 may be branched or cyclized, or may comprise a heteroatom;
each of R 7 and R 8 is independently hydrogen, halogen, C 1-25 alkyl, C 2-25 alkenyl, C 2-25 alkynyl, C 1-25 alkoxy, aralkyl, hydroxyl, amino, nitro or aryl, which may be substituted with other substituent(s), and a part of the carbon chain may be branched or cyclized, or may comprise a heteroatom;
R 2 and R 3 may form a ring;
R 4 and any of R 5 , R 6 , R 7 and R 8 may form a ring;
the bond depicted by a solid line and dashed line represents a carbon—carbon single bond or a carbon—carbon double bond;
at least one of said groups may have a protecting group capable of decomposing in vivo.
6. The compound of claim 5 , wherein each of R 2 , R 3 , R 4 , R 5 , R 6 and R 7 is a hydrogen, R 8 is 1,1-dimethyl-2-propenyl, and the bond depicted by a solid line and a dashed line represents a carbon—carbon double bond.
7. The compound of claim 5 , wherein each of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 is a hydrogen and the bond depicted by a solid line and a dashed line represents a carbon—carbon double bond.
8. The cell divisional inhibitor according to claim 1 , wherein each of R 2 , R 3 , R 4 , R 5 , R 6 and R 7 is a hydrogen, R 8 is 1,1-dimethyl-2-propenyl, and the bond depicted by a solid line and a dashed line represents a carbon—carbon double bond.
9. The cell division inhibitor according to claim 1 , wherein each of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 is a hydrogen and the bond depicted by a solid line and a dashed line represents a carbon—carbon double bond.