Claims for Patent: 7,101,993

Summary for Patent: 7,101,993

Title:	Oligonucleotides containing 2'-O-modified purines
Abstract:	Compounds are provided containing purine nucleotides that bear moieties X at the 2' position thereof wherein X is R.sub.1--(R.sub.2).sub.n; R.sub.1 is C.sub.3-C.sub.20 alkyl, C.sub.4-C.sub.20 alkenyl or C.sub.2-C.sub.20 alkynyl; R.sub.2 is halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides; and n is an integer from 0 to about 6. Such compounds are useful for modulating the synthesis of proteins.
Inventor(s):	Cook; Phillip Dan (San Marcos, CA), McGee; Daniel Peter Claude (Boulder, CA), Guinosso; Charles John (Visia, CA)
Assignee:	ISIS Pharmaceuticals, Inc. (Carlsbad, CA)
Application Number:	07/967,267
Patent Claims:	1. A compound having the structure: ##STR00013## wherein X is R.sub.1--(R.sub.2).sub.n; R.sub.1 is C.sub.2-C.sub.20 alkyl, C.sub.2-C.sub.20 alkenyl, or C.sub.2-C.sub.20 alkynyl and n is 1 to 6; R.sub.2 is halogen, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, imidazole, N-phthalimido, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, or polyether; and either one of T.sub.3 and T.sub.5 is OH, a hydroxyl blocking group, phosphate or an activated phosphate group and the other of T.sub.3 and T.sub.5 is a nucleotide or both T.sub.3 and T.sub.5 are nucleotides. 2. A compound having the structure: ##STR00014## wherein X is R.sub.1--(R.sub.2).sub.n; R.sub.1 is C.sub.1-C.sub.20 alkyl, C.sub.4-C.sub.20 alkenyl, or C.sub.2-C.sub.20 alkynyl; R.sub.2 is halogen, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, imidazole, N-phthalimido, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, or polyether; either one of T.sub.3 and T.sub.5 is OH, a hydroxyl blocking group, phosphate or an activated phosphate group and the other of T.sub.3 and T.sub.5 is a nucleotide, or both T.sub.3 and T.sub.5 are nucleotides; and n is an integer from 1 to 6. 3. The compound of claim 1 wherein R.sub.1 is C.sub.4-C.sub.20 alkyl. 4. The compound of claim 1 wherein R.sub.1 is C.sub.5-C.sub.20 alkyl. 5. The compound of claim 1 wherein R.sub.1 is C.sub.3-C.sub.20 alkyl and n is 1. 6. The compound of claim 1 wherein R.sub.1 is C.sub.4-C.sub.20 alkenyl and n is 1. 7. The compound of claim 1 wherein R.sub.1 is C.sub.2-C.sub.20 alkynyl and n is 1. 8. The compound of claim 1 wherein R.sub.1 is C.sub.2-C.sub.20 alkyl and n is 1 to 6. 9. The compound of claim 1 wherein R.sub.1 is C.sub.2-C.sub.20 alkenyl and n is 1 to 6. 10. The compound of claim wherein R.sub.1 is C.sub.2-C.sub.20 alkynyl and n is 1 to 6. 11. The compound of claim 2 wherein R.sub.1 is C.sub.1-C.sub.20 alkyl. 12. The compound of claim 2 wherein R.sub.1 is C.sub.4-C.sub.20 alkenyl. 13. The compound of claim 2 wherein R.sub.1 is C.sub.2-C.sub.20 alkynyl. ##STR00015## 14. A compound having the structure: wherein X is R.sub.1--(R.sub.2).sub.n; R.sub.1 is C.sub.4-C.sub.20 alkyl, C.sub.4-C.sub.20 alkenyl, or C.sub.2-C.sub.20 alkynyl and n is 0; or R.sub.1 is C.sub.1-C.sub.20 alkyl, C.sub.2-C.sub.20 alkenyl, or C.sub.2-C.sub.20 alkynyl and n is 1 to 6; R.sub.2 is hydroxyl, thiol, keto, carboxyl, or amino; and either one of T.sub.3 and T.sub.5 is OH, a hydroxyl blocking group, phosphate or an activated phosphate group and the other of T.sub.3 and T.sub.5 is a nucleotide or both T.sub.3 and T.sub.5 are nucleotides. 15. A compound having the structure: ##STR00016## wherein X is R.sub.1--(R.sub.2).sub.n; R.sub.1 is C.sub.1-C.sub.20 alkyl, C.sub.4-C.sub.20 alkenyl, or C.sub.2-C.sub.20 alkynyl; R.sub.2 is hydroxyl, thiol, keto, carboxyl, or amino; either one of T.sub.3 and T.sub.5 is OH, a hydroxyl blocking group, phosphate or an activated phosphate group and the other of T.sub.3 and T.sub.5 is a nucleotide, or both T.sub.3 and T.sub.5 are nucleotides; and n is an integer from 0 to 6.