Isis Pharmaceuticals, Inc.

Daniel Peter Claude McGee

Phillip Dan Cook

Charles John Guinosso

Compounds are provided containing purine nucleotides that bear moieties X at the 2' position thereof wherein X is R&#x2014;(R); Ris C-Calkyl, C-Calkenyl or C-Calkynyl; Ris 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.

Oligonucleotides containing 2'-O-modified purines

Processes for preparing 2&prime;-O-alkylated guanosine, uridine, cytidine, and 2,6-diaminopurine 3&prime;-O-phosphoramidites include the steps of alkylating nucleoside precursors, adding suitable blocking groups and phosphitylating. For the guanosine 2&prime;-O-alkylated 3&prime;-O-phosphoramidites, alkylation is effected on 2,6-diamino-9-(&bgr;-D-ribofuranosyl) purine followed by deamination. For uridine 2&prime;-O-alkylated 3&prime;-O-phosphoramidites, alkylation is effect on a dialkyl stannylene derivative of uridine. For cytidine 2&prime;-O-alkylated 3&prime;-O-phosphoramidites, alkylation is effected directly on cytidine. Alkylation is effected directly upon 2,6-diaminopurine.

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Daniel Peter Claude McGee