Patent CA-2125129-A1 (CA)
Title: Dinucleotide analogues, intermediates therefor and oligonucleotides derived therefrom
Inventor: BAXTER ANTHONY D
IPC: A61P31/16
Filed: 1994-06-03
Abstract: ABSTRACT OF THE DISCLOSURE             Dinucleotide Analogues, Intermediates Therefor and Oligonucleotides Derived Therefrom A compound of formula                 I where R1 is hydrogen, R1a or a group of formula    II          R1a is R1b or a protecting group Q, R1b is C1-C20 alkyl, C2-C20 alkenyl, C3-C10 cycloalkyl, C6-C15 aryl, C7-C16 aralkyl or a 5-or 6- membered heterocyclic group attached by a carbon atom in the heterocyclic group to the indicated phosphorus atom, R2 is an unsubstituted or substituted C1-C20 alkyl or C2-C20 alkenyl group, an unsubstituted or substituted C3-C10 cycloalkyl group, an unsubstituted or substituted C6-C15 aryl group, an unsubstituted or substituted C7-C16 aralkyl group, or a 5- or 6-membered heterocyclic group attached by a carbon atom in the heterocyclic group to the indicated phosphorus atom, R3 is hydrogen, halogen, hydroxy, R15, -OR15 or -OSO2R15 R4 is R4a or together with R6 denotes a valence bond, R4a is hydrogen, halogen or R16, R5 is hydrogen, halogen, hydroxy, R17, -OR17, -OCOR17 or -OSO2R17, R6 is hydrogen, halogen or R18, or together with R4 denotes a valence bond, R7 is hydrogen, alkyl-N, N-dialkylphosphoramidyl or R7a, or R7O- together with R8a denotes a C1-C15 hydrocarbylidenedioxy group, R7a is R19, -COR19, -SO2R19 or tri(C1-C15 hydrocarbyl)silyl, R8 is R8a or Z, R8a is hydrogen, halogen, hydroxy, R20, -OR20, -OCOR20, -OSO2R20, or tri(C1-C15 hydrocarbyl)silyloxy, or together with R9 denotes a C1-C15 hydrocarbylidenedioxy group, or together with R7O- denotes a C1-C15 hydrocarbylidenedioxy group, R9 is halogen, hydroxy, -OR21, -OCOR21, -OSO2R21, or B2, or together with R8a denotes a C1-C15 hydrocarbylidenedioxy group, R10 is hydrogen or R10a, R10a is R22, -COR22, -SO2R22 or tri(C1-C15 hydrocarbyl)silyl, R11 is hydrogen, halogen, hydroxy, R23, -OR23, -OCOR23, -OSO2R23 or Z, R12 is hydrogen, halogen or R24, R13 is R13a or Z, R13a is hydrogen, halogen, hydroxy, R25, -OR25, -OCOR25, -OSO2R25, or tri(C1-C15 hydrocarbyl)silyloxy, or together with R14 denotes a C1-C15 hydrocarbylidenedioxy group, R14 is halogen, hydroxy, -OR26, -OCOR26, -OSO2R26, or B1, or together with R13a denotes a C1-C15 hydrocarbylidenedioxy group, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25 and R26 are independently a C1 to C10 aliphatic group, a C3 to C10 cycloaliphatic group, a C6 to C15 aromatic group or a C7-C30 araliphatic group, B1 and B2 are independently each a monovalent nucleoside base radical, and Z is substituted or unsubstituted C6-C10 aryloxythiocarbonyloxy; provided that compounds where simultaneously R1, R3, R4 and R6 are hydrogen, R2 is isopropyl, R5 is methoxy, R7 is methyl, R8 and R9 are each hydroxy or each acetoxy or R8 and R9 together denote isopropylidenedioxy, compounds where simultaneously R1, R3, R4 and R6 are hydrogen, R2 is butyl, R5 is methoxy, R7 is benzyl, R8 and R9 are each hydroxy or each acetoxy or R8 and R9 together denote isopropylidenedioxy, and compounds where simultaneously R1, R3, R4, R5, R6 and R7 are hydrogen, R2 is phenyl and R8 and R9 together denote isopropylidenedioxy are excluded.