IP Library Granted Patent US 7,335,765
Granted Patent B2
US 7,335,765 · App. 09/925,673 · Granted Feb 26, 2008

Nucleoside and oligonucleotide analogues

Assignees: Daiichi Sankyo Company, Limited; Mitsubishi-Kagaku Foods Corporation
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Quick Facts
Patent No.
US 7,335,765
App. No.
09/925,673
Granted
Feb 26, 2008
Kind
B2
Abstract

A compound of the formula (1): wherein R 1 and R 2 are the same or different and represent a hydrogen atom, a hydroxyl protecting group, a phosphate group, or —P(R 3 )R 4 , wherein R 3 and R 4 are the same or different and represent a hydroxyl group, an amino group, an alkoxy group having from 1 to 4 carbon atoms, a cyanoalkoxy group having from 1 to 5 carbon atoms or an amino group substituted by an alkyl group having from 1 to 4 carbon atoms; A represents an alkylene group having from 1 to 4 carbon atoms and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group, a substituted purin-9-yl group or a substituted 2-oxo-pyrimidin-1-yl group having a substituent α selected from the group consisting of a hydroxyl group which may be protected, an alkoxy group having from 1 to 4 carbon atoms, a mercapto group which may be protected, an alkylthio group having from 1 to 4 carbon atoms, an alkoxy group having from 1 to 4 carbon atoms, an amino group which may be protected, a mono- or di-alkylamino group which may be substituted by an alkyl group having from 1 to 4 carbon atoms, an alkyl group having from 1 to 4 carbon atoms and a halogen atom; or a salt thereof.

Claims (99)

1. A compound of formula (1):

wherein:

R 1 and R 2 are the same or different and are selected from the group consisting of hydrogen atoms, hydroxyl protecting groups, phosphate groups, protected phosphate groups and a group of formula —P(R 3 )R 4, wherein R 3 and R 4 are the same or different and are selected from the group consisting of hydroxyl groups, protected hydroxyl groups, mercapto groups, protected mercapto groups, amino groups, alkoxy groups having from 1 to 4 carbon atoms, alkylthio groups having from 1 to 4 carbon atoms, cyanoalkoxy groups having from 1 to 5 carbon atoms and amino groups substituted by an alkyl group having from 1 to 4 carbon atoms;

A represents a methylene group; and

B is selected from the group consisting of unsubstituted purin-9-yl groups, unsubstituted 2-oxo-pyrimidin-1-yl groups, and substituted purin-9-yl groups and substituted 2-oxo-pyrimidin-1-yl groups having at least one substituent α selected from the group consisting of hydroxyl groups, protected hydroxyl groups, alkoxy groups having from 1 to 4 carbon atoms, mercapto groups, protected mercapto groups, alkylthio groups having from 1 to 4 carbon atoms, amino groups, protected amino groups, amino groups substituted by an alkyl group having from 1 to 4 carbon atoms, alkyl groups having from 1 to 4 carbon atoms and halogen atoms;

or a salt thereof.

2. The compound according to claim 1 or a salt thereof, wherein R 1 is selected from the group consisting of hydrogen atoms, aliphatic acyl groups, aromatic acyl groups, methyl groups substituted by from 1 to 3 aryl groups, methyl groups substituted by from 1 to 3 aryl groups the aryl ring of which is substituted by a substituent selected from the group consisting of lower alkyl, lower alkoxy, halogen and cyano groups, and silyl groups.

3. The compound according to claim 1 or a salt thereof, wherein R 1 is selected from the group consisting of hydrogen atoms, acetyl groups, benzoyl groups, benzyl groups, p-methoxybenzyl , dimethoxytrityl , mono-methoxytrityl groups and tert-butyldiphenylsilyl groups.

4. The compound according to claim 1 or a salt thereof, wherein R 2 is selected from the group consisting of hydrogen atoms, aliphatic acyl groups, aromatic acyl groups, methyl groups substituted by from 1 to 3 aryl groups, methyl groups substituted by from 1 to 3 aryl groups the aryl ring of which is substituted by a substituent selected from the group consisting of lower alkyl, lower alkoxy, halogen and cyano groups, silyl groups, phosphoramidite groups, phosphonyl groups, phosphate groups and protected phosphate groups.

5. The compound according to claim 2 or a salt thereof, wherein R 2 is selected from the group consisting of hydrogen atoms, aliphatic acyl groups, aromatic acyl groups, methyl groups substituted by from 1 to 3 aryl groups, methyl groups substituted by from 1 to 3 aryl groups the aryl ring of which is substituted by a substituent selected from the group consisting of lower alkyl, lower alkoxy, halogen and cyano groups, silyl groups, phosphoramidite groups, phosphonyl groups, phosphate groups and protected phosphate groups.

6. The compound according to claim 3 or a salt thereof, wherein R 2 is selected from the group consisting of hydrogen atoms, aliphatic acyl groups, aromatic acyl groups, methyl groups substituted by from 1 to 3 aryl groups, methyl groups substituted by from 1 to 3 aryl groups the aryl ring of which is substituted by a substituent selected from the group consisting of lower alkyl, lower alkoxy, halogen and cyano groups, silyl groups, phosphoramidite groups, phosphonyl groups, phosphate groups and protected phosphate groups.

7. The compound according to claim 1 or a salt thereof, wherein R 2 is selected from the group consisting of hydrogen atoms, acetyl groups, benzoyl groups, benzyl groups, p-methoxybenzyl groups, tert-butyldiphenylsilyl groups, —P(OC 2 H 4 CN) (N(CH(CH 3 ) 2 ) 2 ), —P(OCH 3 ) (N(CH(CH 3 ) 2 ) 2 ), phosphonyl groups, 2-chlorophenyl phosphate groups and 4-chlorophenyl phosphate groups.

8. The compound according to claim 1 or a salt thereof, wherein R 2 is selected from the group consisting of hydrogen atoms, acetyl groups, benzoyl groups, benzyl groups, p-methoxybenzyl groups, tert-butyldiphenylsilyl groups, —P(OC 2 H 4 CN) (N(CH(CH 3 ) 2 ) 2 ), —P(OCH 3 ) (N(CH(CH 3 ) 2 ) 2 ), phosphonyl groups, 2-chlorophenyl phosphate groups and 4-chlorophenyl phosphate groups.

9. The compound according to claim 3 or a salt thereof, wherein R 2 is selected from the group consisting of hydrogen atoms, acetyl groups, benzoyl groups, benzyl groups, p-methoxybenzyl groups, tert-butyldiphenylsilyl groups, —P(OC 2 H 4 CN) (N(CH(CH 3 ) 2 ) 2 ), —P(OCH 3 ) (N(CH(CH 3 ) 2 ) 2 ), phosphonyl groups, 2-chlorophenyl phosphate groups and 4-chlorophenyl phosphate groups.

10. The compound according to claim 1 or a salt thereof, wherein B is selected from the group consisting of 6-aminopurin-9-yl; 6-aminopurin-9-yl, the amino group of which is protected; 2,6-diaminopurin-9-yl; 2-amino-6-chloropurin-9-yl; 2-amino-6-chloropurin-9-yl, the amino group of which is protected; 2-amino-6-fluoropurin-9-yl, 2-amino-6-fluoropurin-9-yl, the amino group of which is protected; 2-amino-6-bromopurin-9-yl; 2-amino-6-bromopurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl; 2-amino-6-hydroxypurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl, the amino group and hydroxyl group of which are protected; 6-amino-2-methoxypurin-9-yl; 6-amino-2-chloropurin-9-yl; 6-amino-2-fluoropurin-9-yl; 2,6-dimethoxypurin-9-yl; 2,6-dichloropurin-9-yl; 6-mercaptopurin-9-yl; 2-oxo-4-amino-pyrimidin-1-yl; 2-oxo-4-amino-pyrimidin-1-yl, the amino group of which is protected; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl, the amino group of which is protected; 4-amino-2-oxo-5-chloro-pyrimidin-1-yl; 2-oxo-4-methoxy-pyrimidin-1-yl; 2-oxo-4-mercapto-pyrimidin-1-yl; 2-oxo-4-hydroxy-pyrimidin-1-yl, 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl; 4amino-5-methyl-2-oxo-pyrimidin-1-yl group and 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group, the amino group of which is protected.

11. The compound according to claim 2 or a salt thereof, wherein B is selected from the group consisting of 6-aminopurin-9-yl; 6-aminopurin-9-yl, the amino group of which is protected; 2,6-diaminopurin-9-yl; 2-amino-6-chloropurin-9-yl; 2-amino-6-chloropurin-9-yl, the amino group of which is protected; 2-amino-6-fluoropurin-9-yl; 2-amino-6-fluoropurin-9-yl, the amino group of which is protected; 2-amino-6-bromopurin-9-yl; 2-amino-6-bromopurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl; 2-amino-6-hydroxypurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl, the amino group and hydroxyl group of which are protected; 6-amino-2-methoxypurin-9-yl; 6-amino-2-chloropurin-9-yl; 6-amino-2-fluoropurin-9-yl; 2,6-dimethoxypurin-9-yl; 2,6-dichloropurin-9-yl; 6-mercaptopurin-9-yl; 2-oxo-4-amino-pyrimidin-1-yl; 2-oxo-4-amino-pyrimidin-1-yl, the amino group of which is protected; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl, the amino group of which is protected; 4-amino-2-oxo-5-chloro-pyrimidin-1-yl; 2-oxo-4-methoxy-pyrimidin-1-yl; 2-oxo-4-mercapto-pyrimidin-1-yl; 2-oxo-4-hydroxy-pyrimidin-1-yl; 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl; 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group and 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group, the amino group of which is protected.

12. The compound according to claim 3 or a salt thereof, wherein B is selected from the group consisting of 6-aminopurin-9-yl; 6-aminopurin-9-yl, the amino group of which is protected; 2,6-diaminopurin-9-yl; 2-amino-6-chloropurin-9-yl; 2-amino-6-chloropurin-9-yl, the amino group of which is protected; 2-amino-6-fluoropurin-9-yl; 2-amino-6-fluoropurin-9-yl, the amino group of which is protected; 2-amino-6-bromopurin-9-yl; 2-amino-6-bromopurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl; 2-amino-6-hydroxypurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl, the amino group and hydroxyl group of which are protected; 6-amino-2-methoxypurin-9-yl; 6-amino-2-chloropurin-9-yl; 6-amino-2-fluoropurin-9-yl; 2,6-dimethoxypurin-9-yl; 2,6-dichloropurin-9-yl; 6-mercaptopurin-9-yl; 2-oxo-4-amino-pyrimidin-1-yl; 2-oxo-4-amino-pyrimidin-1-yl, the amino group of which is protected; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl, the amino group of which is protected; 4-amino-2-oxo-5-chloro-pyrimidin-1-yl; 2-oxo-4-methoxy-pyrimidin-1-yl; 2-oxo-4-mercapto-pyrimidin-1-yl; 2-oxo-4-hydroxy-pyrimidin-1-yl; 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl; 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group and 4-amino-5-methyl-2-oxo-pyrimidin-1-yl groups, the amino group of which is protected.

13. The compound according to claim 4 or a salt thereof, wherein B is selected from the group consisting of 6-aminopurin-9-yl; 6-aminopurin-9-yl, the amino group of which is protected; 2,6-diaminopurin-9-yl; 2-amino-6-chloropurin-9-yl; 2-amino-6-chloropurin-9-yl, the amino group of which is protected; 2-amino-6-fluoropurin-9-yl; 2-amino-6-fluoropurin-9-yl, the amino group of which is protected; 2-amino-6-bromopurin-9-yl; 2-amino-6-bromopurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl; 2-amino-6-hydroxypurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl, the amino group and hydroxyl group of which are protected; 6-amino-2-methoxypurin-9-yl; 6-amino-2-chloropurin-9-yl; 6-amino-2-fluoropurin-9-yl; 2,6-dimethoxypurin-9-yl; 2,6-dichloropurin-9-yl; 6-mercaptopurin-9-yl; 2-oxo-4-amino-pyrimidin-1-yl; 2-oxo-4-amino-pyrimidin-1-yl, the amino group of which is protected; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl, the amino group of which is protected; 4-amino-2-oxo-5-chloro-pyrimidin-1-yl; 2-oxo-4-methoxy-pyrimidin-1-yl; 2-oxo-4-mercapto-pyrimidin-1-yl; 2-oxo-4-hydroxy-pyrimidin-1-yl; 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl; 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group and 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group, the amino group of which is protected.

14. The compound according to claim 5 or a salt thereof, wherein B is selected from the group consisting of 6-aminopurin-9-yl; 6-aminopurin-9-yl, the amino group of which is protected; 2,6-diaminopurin-9-yl; 2-amino-6-chloropurin-9-yl; 2-amino-6-chloropurin-9-yl, the amino group of which is protected; 2-amino-6-fluoropurin-9-yl; 2-amino-6-fluoropurin-9-yl, the amino group of which is protected; 2-amino-6-bromopurin-9-yl; 2-amino-6-bromopurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl; 2-amino-6-hydroxypurin9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl, the amino group and hydroxyl group of which are protected; 6-amino-2-methoxypurin-9-yl; 6-amino-2-chloropurin-9-yl; 6-amino-2-fluoropurin-9-yl; 2,6-dimethoxypurin-9-yl; 2,6-dichloropurin-9-yl; 6-mercaptopurin-9-yl; 2-oxo-4-amino-pyrimidin-1-yl; 2-oxo-4-amino-pyrimidin-1-yl, the amino group of which is protected; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl, the amino group of which is protected; 4-amino-2-oxo-5-chloro-pyrimidin-1-yl; 2-oxo-4-methoxy-pyrimidin-1-yl; 2-oxo-4-mercapto-pyrimidin-1-yl; 2-oxo-4-hydroxy-pyrimidin-1-yl; 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl; 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group and 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group, the amino group of which is protected.

15. The compound according to claim 6 or a salt thereof, wherein B is selected from the group consisting of 6-aminopurin-9-yl; 6-aminopurin-9-yl, the amino group of which is protected; 2,6-diaminopurin-9-yl; 2-amino-6-chloropurin-9-yl; 2-amino-6-chloropurin-9-yl, the amino group of which is protected; 2-amino-6-fluoropurin-9-yl; 2-amino-6-fluoropurin-9-yl, the amino group of which is protected; 2-amino-6-bromopurin-9-yl; 2-amino-6-bromopurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl; 2-amino-6-hydroxypurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl, the amino group and hydroxyl group of which are protected; 6-amino-2-methoxypurin-9-yl; 6-amino-2-chloropurin-9-yl; 6-amino-2-fluoropurin-9-yl; 2,6-dimethoxypurin-9-yl; 2,6-dichloropurin-9-yl; 6-mercaptopurin-9-yl; 2-oxo-4-amino-pyrimidin-1-yl; 2-oxo-4-amino-pyrimidin-1-yl, the amino group of which is protected; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl, the amino group of which is protected; 4-amino-2-oxo-5-chloro-pyrimidin-1-yl; 2-oxo-4-methoxy-pyrimidin-1-yl; 2-oxo-4-mercapto-pyrimidin-1-yl; 2-oxo-4-hydroxy-pyrimidin-1-yl; 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl; 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group and 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group, the amino group of which is protected.

16. The compound according to claim 7 or a salt thereof, wherein B is selected from the group consisting of 6-aminopurin-9-yl; 6-aminopurin-9-yl, the amino group of which is protected; 2,6-diaminopurin-9-yl; 2-amino-6-chloropurin-9-yl; 2-amino-6-chloropurin-9-yl, the amino group of which is protected; 2-amino-6-fluoropurin-9-yl; 2-amino-6-fluoropurin-9-yl, the amino group of which is protected; 2-amino-6-bromopurin-9-yl; 2-amino-6-bromopurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl; 2-amino-6-hydroxypurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl, the amino group and hydroxyl group of which are protected; 6-amino-2-methoxypurin-9-yl; 6-amino-2-chloropurin-9-yl; 6-amino-2-fluoropurin-9-yl; 2,6-dimethoxypurin-9-yl; 2,6-dichloropurin-9-yl; 6-mercaptopurin-9-yl; 2-oxo-4-amino-pyrimidin-1-yl; 2-oxo-4-amino-pyrimidin-1-yl, the amino group of which is protected; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl, the amino group of which is protected; 4-amino-2-oxo-5-chloro-pyrimidin-1-yl; 2-oxo-4-methoxy-pyrimidin-1-yl; 2-oxo-4-mercapto-pyrimidin-1-yl; 2-oxo-4-hydroxy-pyrimidin-1-yl; 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl; 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group and 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group, the amino group of which is protected.

17. The compound according to claim 8 or a salt thereof, wherein B is selected from the group consisting of 6-aminopurin-9-yl; 6-aminopurin-9-yl, the amino group of which is protected; 2,6-diaminopurin-9-yl; 2-amino-6-chloropurin-9-yl; 2-amino-6-chloropurin-9-yl, the amino group of which is protected; 2-amino-6-fluoropurin-9-yl; 2-amino-6-fluoropurin-9-yl, the amino group of which is protected; 2-amino-6-bromopurin-9-yl; 2-amino-6-bromopurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl; 2-amino-6-hydroxypurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl, the amino group and hydroxyl group of which are protected; 6-amino-2-methoxypurin-9-yl; 6-amino-2-chloropurin-9-yl; 6-amino-2-fluoropurin-9-yl; 2,6-dimethoxypurin-9-yl; 2,6-dichloropurin-9-yl; 6-mercaptopurin-9-yl; 2-oxo-4-amino-pyrimidin-1-yl; 2-oxo-4-amino-pyrimidin-1-yl, the amino group of which is protected; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl, the amino group of which is protected; 4-amino-2-oxo-5-chloro-pyrimidin-1-yl; 2-oxo-4-methoxy-pyrimidin-1-yl; 2-oxo-4-mercapto-pyrimidin-1-yl; 2-oxo-4-hydroxy-pyrimidin-1-yl; 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl; 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group and 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group, the amino group of which is protected.

18. The compound according to claim 9 or a salt thereof, wherein B is selected from the group consisting of 6-aminopurin-9-yl; 6-aminopurin-9-yl, the amino group of which is protected; 2,6-diaminopurin-9-yl; 2-amino-6-chloropurin-9-yl; 2-amino-6-chloropurin-9-yl, the amino group of which is protected; 2-amino-6-fluoropurin-9-yl; 2-amino-6-fluoropurin-9-yl, the amino group of which is protected; 2-amino-6-bromopurin-9-yl; 2-amino-6-bromopurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl; 2-amino-6-hydroxypurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl, the amino group and hydroxyl group of which are protected; 6-amino-2-methoxypurin-9-yl; 6-amino-2-chloropurin-9-yl; 6-amino-2-fluoropurin-9-yl; 2,6-dimethoxypurin-9-yl; 2,6-dichloropurin-9-yl; 6-mercaptopurin-9-yl; 2-oxo-4-amino-pyrimidin-1-yl; 2-oxo-4-amino-pyrimidin-1-yl, the amino group of which is protected; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl, the amino group of which is protected; 4-amino-2-oxo-5-chloro-pyrimidin-1-yl; 2-oxo-4-methoxy-pyrimidin-1-yl; 2-oxo-4-mercapto-pyrimidin-1-yl; 2-oxo-4-hydroxy-pyrimidin-1-yl; 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl; 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group and 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group, the amino group of which is protected.

19. The compound according to claim 1 or a salt thereof, wherein B is selected from the group consisting of 6-benzoylaminopurin-9-yl, adeninyl, 2-isobutyrylamino-6-hydroxypurin-9-yl, guaninyl, 2-oxo-4-benzoylamino-pyrimidin-1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-pyrimidin-1-yl, 5-methylcytosinyl, uracinyl and thiminyl groups.

20. The compound according to claim 2 or a salt thereof, wherein B is selected from the group consisting of 6-benzoylaminopurin-9-yl, adeninyl, 2-isobutyrylamino-6-hydroxypurin-9-yl, guaninyl, 2-oxo-4-benzoylamino-pyrimidin-1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-pyrimidin-1-yl, 5-methylcytosinyl, uracinyl and thyminyl groups.

21. The compound according to claim 3 or a salt thereof, wherein B is selected from the group consisting of 6-benzoylaminopurin-9-yl, adeninyl, 2-isobutyrylamino-6-hydroxypurin-9-yl, guaninyl, 2-oxo-4-benzoylamino-pyrimidin-1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-pyrimidin-1-yl, 5-methylcytosinyl, uracinyl and thyminyl groups.

22. The compound according to claim 4 or a salt thereof, wherein B is selected from the group consisting of 6-benzoylaminopurin-9-yl, adeninyl, 2-isobutyrylamino-6-hydroxypurin-9-yl, guaninyl, 2-oxo-4-benzoylamino-pyrimidin-1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-pyrimidin-1-yl, 5-methylcytosinyl, uracinyl and thyminyl groups.

23. The compound according to claim 5 or a salt thereof, wherein B is selected from the group consisting of 6-benzoylaminopurin-9-yl, adeninyl, 2-isobutyrylamino-6-hydroxypurin-9-yl, guaninyl, 2-oxo-4-benzoylamino-pyrimidin-1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-pyrimidin-1-yl, 5-methylcytosinyl, uracinyl and thyminyl groups.

24. The compound according to claim 6 or a salt thereof, wherein B is selected from the group consisting of 6-benzoylaminopurin-9-yl, adeninyl, 2-isobutyrylamino-6-hydroxypurin-9-yl, guaninyl, 2-oxo-4-benzoylamino-pyrimidin-1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-pyrimidin-1-yl, 5-methylcytosinyl, uracinyl and thyminyl groups.

25. The compound according to claim 7 or a salt thereof, wherein B is selected from the group consisting of 6-benzoylaminopurin-9-yl, adeninyl, 2-isobutyrylamino-6-hydroxypurin-9-yl, guaninyl, 2-oxo-4-benzoylamino-pyrimidin-1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-pyrimidin-1-yl, 5-methylcytosinyl, uracinyl and thyminyl groups.

26. The compound according to claim 8 or a salt thereof, wherein B is selected from the group consisting of 6-benzoylaminopurin-9-yl, adeninyl, 2-isobutyrylamino-6-hydroxypurin-9-yl, guaninyl, 2-oxo-4-benzoylamino-pyrimidin-1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-pyrimidin-1-yl, 5-methylcytosinyl, uracinyl and thyminyl groups.

27. The compound according to claim 9 or a salt thereof, wherein B is selected from the group consisting of 6-benzoylaminopurin-9-yl, adeninyl, 2-isobutyrylamino-6-hydroxypurin-9-yl, guaninyl, 2-oxo-4-benzoylamino-pyrimidin-1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-pyrimidin-1-yl, 5-methylcytosinyl, uracinyl and thyminyl groups.

28. A compound or a salt thereof selected from the group consisting of

2′-O,4′-C-ethyleneguanosine,

2′-O,4′-C-ethyleneadenosine,

3′,5′-di-O-benzyl-2′-O,4′-C-ethylene-6-N-benzoyladenosine,

3′,5′-di-O-benzyl-2′-O,4′-C-ethylene-2-N-isobutyrylguanosine,

5′-O-dimethoxytrityl-2′-O,4′-C-ethylene-6-N-benzoyladenosine,

5′-O-dimethoxytrityl-2′-O,4′-C-ethylene-2-N-isobutyrylguanosine,

2′-O,4′-C-ethylene-2-N-isobutyrylguanosine,

2′O,4′-C-ethylene-6-N-benzoyladenosine,

5′-O-dimethoxytrityl-2′-O,4′-C-ethylene-6-N-benzoyladenosine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite,

5′-O-dimethoxytrityl-2′-O,4′-C-ethylene-2-N-isobutyrylguanosine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite,

2′-O,4′-C-ethyleneuridine,

2′-O,4′-C-ethylene-5-methyluridine,

2′-O,4′-C-ethylenecytidine,

2′-O,4′-C-ethylene-5-methylcytidine,

3′,5′-di-O-benzyl-2′-O,4′-C-ethyleneuridine,

5′-O-dimethoxytrityl-2′-O,4′-C-ethyleneuridine,

3′,5′-di-O-benzyl-2′-O,4′-C-ethylene-5-methyluridine,

5′-O-dimethoxytrityl-2′-O,4′-C-ethylene-5-methyluridine,

3′,5′-di-O-benzyl-2′-O,4′-C-ethylene-4-N-benzoylcytidine,

5′-O-dimethoxytrityl-2′-O,4′-C-ethylene-4-N-benzoylcytidine,

3′,5′-di-O-benzyl-2′-O,4′-C-ethylene-4-N-benzoyl-5-methylcytidine,

5′-O-dimethoxytrityl-2′-O,4′-C-ethylene-4-N-benzoyl-5-methylcytidine,

2′-O,4′-C-ethylene-4-N-benzoylcytidine,

2′-O,4′-C-ethylene-4-N-benzoyl-5-methylcytidine,

5′-O-dimethoxytrityl-2′-O,4′-C-ethylene-uridine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite,

5′-O-dimethoxytrityl-2′-O,4′-C-ethylene-5-methyluridine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite,

5′-O-dimethoxytrityl-2′-O,4′-C-ethylene-4-N-benzoylcytidine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite, and

5′-O-dimethoxytrityl-2′-O,4′-C-ethylene-4-N-benzoyl-5-methylcytidine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite.

29. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethylene-5-methyluridine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite or a salt thereof.

30. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethylene-6-N-benzoyladenosine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite or a salt thereof.

31. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethylene-2-N-isobutyrylguanosine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite or a salt thereof.

32. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethylene-uridine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite or a salt thereof.

33. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethylene-4-N-benzoylcytidine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite or a salt thereof.

34. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethylene-4-N-benzoyl-5-methylcytidine-3′-O-(2-cyanoethyl N,N-diisopropyl)phosphoramidite or a salt thereof.

35. An oligonucleotide analogue comprising two or more nucleoside units wherein at least one of said nucleoside units is a structure of the formula (2):

wherein:

A represents a methylene group; and

B is selected from the group consisting of an unsubstituted purin-9-yl group, an unsubstituted 2-oxo-pyrimidin-1-yl group, a purin-9-yl group substituted with at least one substituent α and a 2-oxo-pyrimidin-1-yl group substituted with at least one substituent α, said substituent α being selected from the group consisting of an unprotected hydroxyl group, a protected hydroxyl group, an alkoxy group having from 1 to 4 carbon atoms, an unprotected mercapto group, a protected mercapto group, an alkylthio group having from 1 to 4 carbon atoms, an unprotected amino group, a protected amino group, an amino group substituted by an alkyl group having from 1 to 4 carbon atoms, an alkyl group having from 1 to 4 carbon atoms and a halogen atom; or a salt thereof.

36. The oligonucleotide analogue according to claim 35 or a salt thereof, which comprises up to 100 nucleoside units and wherein nucleoside units are bonded to each other through a phosphodiester bond or a phosphorothioate bond.

37. The oligonucleotide analogue according to claim 35 or a salt thereof which comprises 2 to 50 nucleoside units; and when said oligonucleotide analogue contains two or more nucleoside units of the structure of said formula (2), said nucleoside units of the structure of formula (2) are the same or different, and wherein said salt is a pharmaceutically acceptable salt.

38. The oligonucleotide analogue according to claim 37 or a salt thereof which comprises 10 to 30 nucleoside units.

39. The oligonucleotide analogue according to claim 35 or a salt thereof, wherein said nucleoside units are bonded to each other through a phosphoric acid diester bond or a phosphorothioate bond.

40. The oligonucleotide analogue according to claim 35 or a salt thereof, wherein B is selected from the group consisting of 6-aminopurin-9-yl; 6-aminopurin-9-yl, the amino group of which is protected; 2,6-diamino-purin-9-yl; 2-amino-6-chloropurin-9-yl, 2-amino-6-chloropurin-9-yl, the amino group of which is protected; 2-amino-6-fluoropurin-9-yl; 2amino-6-fluoropurin-9-yl, the amino group of which is protected; 2-amino-6-bromopurin-9-yl; 2-amino-6-bromopurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl; 2-amino-6-hydroxypurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl, the amino group and hydroxyl group of which are protected; 6-amino-2-methoxypurin-9-yl; 6-amino-2-chloropurin-9-yl; 6-amino-2-fluoropurin-9-yl; 2,6-dimethoxypurin-9-yl; 2,6-dichloro-purin-9-yl; 6-mercaptopurin-9-yl; 2-oxo-4-amino-pyrimidin-1-yl; 2-oxo-4-amino-pyrimidin-1-yl, the amino group of which is protected; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl, the amino group of which is protected; 4-amino-2-oxo-5-chloro-pyrimidin-1-yl; 2-oxo-4-methoxy-pyrimidin-1-yl; 2-oxo-4-mercapto-pyrimidin-1-yl; 2-oxo-4-hydroxy-pyrimidin-1-yl; 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl; 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group and 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group, the amino group of which is protected.

41. The oligonucleotide analogue according to claim 35 or a salt thereof, wherein B is selected from the group consisting of 6-benzoylaminopurin-9-yl, adeninyl, 2-isobutyrylamino-6-hydroxypurin-9-yl, guaninyl, 2-oxo-4-benzoylamino-pyrimidin-1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-pyrimidin-1yl, 5-methylcytosinyl, uracinyl and thyminyl groups.

42. A pharmaceutical composition comprising a pharmaceutically effective amount of a pharmacologically active compound together with a carrier therefor, wherein said pharmacologically active compound is an oligonucleotide analogue comprising two or more nucleoside units, wherein at least one of said nucleoside units is a structure of the formula (2):

wherein:

A represents a methylene group; and

B is selected from the group consisting of an unsubstituted purin-9-yl group, an unsubstituted 2-oxo-pyrimidin-1-yl group, a purin-9-yl group substituted with at least one substituent α and a 2-oxo-pyrimidin-1-yl group substituted with at least one substituent α, said substituent α being selected from the group consisting of an unprotected hydroxyl group, a protected hydroxyl group, an alkoxy group having from 1 to 4 carbon atoms, an unprotected mercapto group, a protected mercapto group, an alkylthio group having from 1 to 4 carbon atoms, an unprotected amino group, a protected amino group, an amino group substituted by an alkyl group having from 1 to 4 carbon atoms, an alkyl group having from 1 to 4 carbon atoms and a halogen atom; or a pharmacologically acceptable salt thereof.

43. A pharmaceutical composition according to claim 42 , wherein B is selected from the group consisting of 6-aminopurin-9-yl; 6-aminopurin-9-yl, the amino group of which is protected; 2,6-diamino-purin-9-yl; 2-amino-6-chloropurin-9-yl; 2-amino-6-chloropurin-9-yl, the amino group of which is protected; 2-amino-6-fluoropurin-9-yl; 2-amino-6-fluoropurin-9-yl, the amino group of which is protected; 2-amino-6-bromopurin-9-yl; 2-amino-6-bromopurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl; 2-amino-6-hydroxypurin-9-yl, the amino group of which is protected; 2-amino-6-hydroxypurin-9-yl, the amino group and hydroxyl group of which are protected; 6-amino-2-methoxypurin-9-yl; 6-amino-2-chloropurin-9-yl, 6-amino-2-fluoropurin-9-yl; 2,6-dimethoxypurin-9-yl; 2,6-dichloro-purin-9-yl; 6-mercaptopurin-9-yl; 2-oxo-4-amino-pyrimidin-1-yl; 2-oxo-4-amino-pyrimidin-1-yl, the amino group of which is protected; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl; 2-oxo-4-amino-5-fluoro-pyrimidin-1-yl, the amino group of which is protected; 4-amino-2-oxo-5-chloro-pyrimidin-1-yl; 2-oxo-4-methoxy-pyrimidin-1-yl; 2-oxo-4-mercapto-pyrimidin-1-yl; 2-oxo-4-hydroxy-pyrimidin-1-yl; 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl; 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group and 4-amino-5-methyl-2-oxo-pyrimidin-1-yl group, the amino group of which is protected.

44. A pharmaceutical composition according to claim 42 , wherein B is selected from the group consisting of 6-benzoylaminopurin-9-yl, adeninyl, 2-isobutyrylamino-6-hydroxypurin-9-yl, guaninyl, 2-oxo-4-benzoylamino-pyrimidin-1-yl, cytosinyl, 2-oxo-5-methyl-4-benzoylamino-pyrimidin1-yl, 5-methylcytosinyl, uracinyl and thyminyl groups.

45. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethylene-6-N-benzoyladenosine or a salt thereof.

46. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethylene-2-N-isobutyrylguanosine or a salt thereof.

47. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethyleneuridine or a salt thereof.

48. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethylene-5-methyluridine or a salt thereof.

49. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethylene-4-N-benzoylcytidine or a salt thereof.

50. 5′-O-Dimethoxytrityl-2′-O,4′-C-ethylene-4-N-benzoyl-5-methylcytidine or a salt thereof.

51. The oligonucleotide analogue according to claim 35 or a salt thereof, wherein B is a 6-an adeninyl group.

52. The oligonucleotide analogue according to claim 35 or a salt thereof, wherein B is a 2-guaninyl group.

53. The oligonucleotide analogue according to claim 35 or a salt thereof, wherein B is a uracinyl group.

54. The oligonucleotide analogue according to claim 35 or a salt thereof, wherein B is a 2-oxo-4-hydroxy-5-methylpyrimidin-1-yl group.

55. The oligonucleotide analogue according to claim 35 or a salt thereof, wherein B is a 2-oxo-4-cytosinyl group.

56. The oligonucleotide analogue according to claim 35 or a salt thereof, wherein B is a 5-methylcytosinyl group.

57. The compound according to claim 2 or a salt thereof, wherein R 1 is selected from the group consisting of benzyl, 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl and 4-methoxybenzyl.

58. The compound according to claim 4 or a salt thereof, wherein R 2 is selected from the group consisting of benzyl, 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl and 4-methoxybenzyl.

59. The compound according to claim 5 or a salt thereof, wherein R 2 is selected from the group consisting of benzyl, 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl and 4 methoxybenzyl.

60. The compound according to claim 6 or a salt thereof, wherein R 2 is selected from the group consisting of benzyl, 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl and 4-methoxybenzyl.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 15, 2010
From: MITSUBISHI-KAGAKU FOODS CORPORATION
To: DAIICHI SANKYO COMPANY, LIMITED
Reel/Frame 025137/0518 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 12, 2007
From: SANKYO LIFETECH COMPANY, LIMITED
To: MITSUBISHI-KAGAKU FOODS CORPORATION
Reel/Frame 019555/0631 →
MERGER Recorded Jul 9, 2007
From: SANKYO COMPANY, LIMITED
To: DAIICHI SANKYO COMPANY, LIMITED
Reel/Frame 019531/0076 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 9, 2004
From: SANKYO COMPANY, LIMITED
To: SANKYO LIFETECH COMPANY LIMITED; SANKYO COMPANY, LIMITED
Reel/Frame 014856/0158 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 13, 2001
From: KANEKO, MASAKATSU; MORITA, KOJI; IMANISHI, TAKESHI
To: SANKYO COMPANY, LIMITED
Reel/Frame 012415/0995 →
Priority Claims (1)
JP 11-033863 · Feb 12, 1999 · national
Continuity (2)
Continuation In Part PCTJP000072500 · Feb 10, 2000
Related Publication 20020147332A1 · Oct 10, 2002