RIBOFURANOSYL NUCLEOSIDES

摘要

1,232,661. Ribofuranosyl nucleosides. MERCK & CO. Inc. 5 Aug., 1968 [8 Aug., 1967], No. 37294/68. Heading C2C. Novel compounds I or 21, 31-isopropylidene or 2131-di-O acetyl derivatives thereof in which Y is -S-COCH 3 , -CNS, -NRR1, -N(#O)=CCH 32 , -N 3 , -NHCOR, -NHCOR11, -NHCOOR0, -NHCONRR1, -NHCSNRR1, -NHCN, or -NHC-(=NH)-NRR1; R0 is H or 2-5 C alkyl; R and R1 are H or 1-5C alkyl; R11 is 1- or 2-adamantyl and Z is a purine residue II or a pyrimidine residue III in which J is H, halo, OH, SH, 1-5 C alkylthio, benzylthio, amino or 1-5 C alkyl-substituted amino, isopentenylamino or benzylamino; K is H, halo, OH, SH, 2-5 C alkylthio, benzylthio, amino or 1-5 C alkyl-substituted amino, isopentenylamino or benzylamino; L is 1-5 C alkoxy, OH, NH 2 or 1-5 C alkyl-substituted amino and M is H, 1-5 C alkyl, halo, 1-5 C haloalkyl, amino or 1-5 C alkyl-substituted amino, benzylamino, SH, 1-5 C alkylthio or benzylthio, with the provisos that in the case of the 21,31-dihydroxy compounds, when Y is azido, amino or acetamido Z is not derived from an unsubstituted adenine, guanine or uracil or an N-alkyl or alkenyl-adenine residue as well as the novel compound 51-azido-51-deoxy-N6-(2- isopentenyl)-adenosine are prepared by (1) reacting a compound IV where X is alkylsulphonyl or arylsulphonyl with an alkali metal thioacetate, thiocyanate or azide; amine or acetone oxime to give a product I where Y is -SCOCH 3 , -CNS, -N 3 , -NRR1 or -N(#0)=C(CH 3 ) 2 and when Y is N 3 optionally reducing the product to give one in which Y is NH 2 ; or (2) reacting a compound V with an alkanoyl halide or anhydride, adamantoyl halide, alkyl chloroformate, alkali metal cyanate or thiocyanate or a cyanogen halide to give I where Y is -NHCOR, -NHCOR11, -NHCONRR1, -NHCSNRR1 or -NHCN and when Y is -NHCN optionally reacting the product with NH 3 or an amine to give I where Y is -NHC(=NH)NRR1 followed in either of (1) or (2) by conversion to the 21,31dihydroxy compound if desired. Intermediates isolated are 51-acetylthio-51- deoxy - N6 - formyl - 21,31 - O - isopropylideneadenosine; 51 - deoxy - N6 - formyl - 5 - thiocyanoadenosine; N6 - formyl - 51 - isopropylideneamino - 21,31 - O - isopropylidene - adenosine N - 51 - oxide; N6 - (2 - isopentenyl) - 21, 31 - O - isopropylideneadenosine; N6 - (2 - isopentenyl) - 21,31 - O - isopropylidene - 51 - tosyladenosine and 6 - methylthio - 9 - (2,3 - O - isopropylidene - 5 - tosyl - # - D - ribofuranosyl)- purine. Pharmaceutical compositions useful as antiviral agents, antimetabolites, and cell growth inhibitors comprise a compound I together with a suitable excipient.