Synthesis of 3-deazapurines

• US 5,948,903 A
• Filed: 05/08/1998
• Issued: 09/07/1999
• Est. Priority Date: 01/11/1991
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Andrews, Robert S., Cook, P. Dan, Acevedo, Oscar L.
• Primary Examiner(s): Wilson, James O.
• Application Number:
  US09/074,503
• Time in Patent Office: 487 Days
• Field of Search: 536/27.13, 536/27.3, 536/27.6, 536/27.7, 536/25.34, 536/25.33, 536/26.7, 544/253, 544/242, 544/245, 544/278, 544/279, 546/118
• US Class Current: 536/25.34
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids

Abstract

This invention relates to compounds based on the 3-deazapurines ring system and to methods for making such compounds. The invention also generally relates to the field of "antisense" agents, agents that are capable of specific hybridization with a nucleotide sequence of an RNA. The 3-deazapurine-containing compounds of this invention can be useful for modulating the activity of RNA when incorporated into oligonucleotides. Oligonucleotides and their analogs are used for a variety of therapeutic and diagnostic purposes, such as treating diseases, regulating gene expression in experimental systems, assaying for RNA and for RNA products through the employment of antisense interactions with such RNA, diagnosing diseases, modulating the production of proteins and cleaving RNA in site specific fashions.

Claims

1. A nucleocide having the formula:

##STR7## wherein G is CH or N;

R₁ is NH₂, alkyl having from one to about 12 carbons, substituted alkyl having from one to about 12 carbons, alkenyl having from 2 to about 12 carbons, substituted alkenyl having from 2 to about 12 carbons, aralkyl having from about 6 to about 30 carbons, or amino, R₂ is amino, alkyl having from 1 about 12 carbons, substituted alkyl having from 1 about 12 carbons, alkenyl having from 2 to about 12 carbons, substituted alkenyl having from 2 to about 12 carbons, or aralkyl having from about 6 to about 30 carbons; and

Y is a sugar having an activated phosphate group.

2. The compound of claim 1 wherein said sugar is ribose or deoxyribose.

3. The compound of claim 2 wherein R₂ is amino.

4. The compound of claim 2 wherein said activated phosphorus group is a phosphoramidite group.

5. The compound of claim 1 wherein R₁ is alkenyl having up to about 12 carbon atoms.

6. The compound of claim 1 wherein R₁ is aralkyl having from about 6 to about 30 carbon atoms.

7. The compound of claim 2 wherein R₁ is alkyl having up to about 12 carbon atoms.

8. The compound of claim 2 wherein R₁ is alkenyl having up to about 12 carbon atoms.

9. The compound of claim 2 wherein R₁ is aralkyl having from about 6 to about 30 carbon atoms.

10. The compound of claim 1 wherein G is N;

R₁ is alkyl;

R₂ is amino; and

said sugar is ribose or deoxyribose.

11. The compound of claim 1 wherein G is N;

R₁ is alkenyl;

R₂ is amino; and

said sugar is ribose or deoxyribose.

12. The compound of claim 1 wherein G is N;

R₁ is aralkyl;

R₂ is amino; and

said sugar is ribose or deoxyribose.

13. The compound of claim 1 wherein G is N;

R₁ is 1-methyl octane, 1-propene, phenyl methyl, or naphthylmethyl;

R₂ is amino; and

said sugar is ribose or deoxyribose.

14. A compound having the formula:

##STR8## wherein G is CH or N;

R₃ is H, NH₂, alkyl having 1 to about 12 carbons, substituted alkyl having 1 to about 12 carbons, alkenyl having from 2 to about 12 carbons, substituted alkenyl having from 2 to about 12 carbons, aralkyl having from about 6 to about 30 carbons, or amino;

R₄ is NH₂, alkyl having 1 to about 12 carbons, substituted alkyl having 1 to about 12 carbons, alkenyl having from 2 to about 12 carbons, substituted alkenyl having from 2 to about 12 carbons, aralkyl having from about 6 to about 30 carbons, or amino; and

Y is a sugar having an activated phosphate group;

provided that when R₃ is H, R₄ is not NH₂.

15. The compound of claim 14 wherein said sugar is ribose or deoxyribose.

16. The compound of claim 14 wherein said activated phosphorus group is a phosphoramidite group.

17. The compound of claim 14 wherein R₃ is alkenyl having up to about 12 carbon atoms.

18. The compound of claim 14 wherein R₃ is aralkyl having from about 6 to about 30 carbon atoms.

19. The compound of claim 16 wherein R₃ is alkyl having up to about 12 carbon atoms.

20. The compound of claim 15 wherein R₃ is alkenyl having up to about 12 carbon atoms.

21. The compound of claim 15 wherein R₃ is aralkyl having up to about 6 to 30 carbon atoms.

22. The compound of claim 15 wherein G is N;

R₃ is alkyl;

R₄ is NH₂ ; and

said sugar is ribose or deoxyribose.

23. The compound of claim 14 wherein G is N;

R₃ is alkenyl;

R₄ is NH₂ ; and

said sugar is ribose or deoxyribose.

24. The compound of claim 14 wherein G is N;

R₃ is aralkyl;

R₄ is NH₂ ; and

said sugar is ribose or deoxyribose.

25. The compound of claim 14 wherein G is N;

R₃ is 1-methyl octane, 1-propene, phenyl methyl, or naphthylmethyl;

R₄ is NH₂ ; and

said sugar is ribose or deoxyribose.