Oligoribonucleoside and oligodeoxyribonucleoside boranophosphates

An oligonucleoside boronophosphate, or a salt thereof, having the formula, from 5' to 3' of:

• ##STR10## wherein:
• n is an integer having a value of from 0 to 50;
• W is selected from the group consisting of .dbd.O, .dbd.S, --OR', --SR', and --OCH.sub.2 CH.sub.2 CN, wherein R' is C1 to C3 alkyl;
• X.sub.1 and X.sub.n+1 are each independently selected from the group consisting of --OH, --BH.sub.3, --BH.sub.2 R.sub.1, --BHR.sub.1 R.sub.2 and --BHR.sub.1 R.sub.2 and --BR.sub.1 R.sub.2 R.sub.3, subject to the proviso that at least one of X.sub.1 and X.sub.n+1 is not --OH;
• R.sub.1 is selected from the group consisting of --R.sub.4, --COOH, --COOR.sub.4, --CONHR.sub.4, --CON (R.sub.4).sub.2, --CN.sup.+ R.sub.4 Z.sup.-, --CN, carboxycholesteryl and carboxybenzyl, wherein R.sub.4 is C1 to C18 alkyl and Z.sup.- is an anion;
• R.sub.2 is selected from the group consisting of --R.sub.5, --COOH, --COOR.sub.5, --CONHR.sub.5, --CON (R.sub.5).sub.2, --CN.sup.+ R.sub.5 Z.sup.-, --CN, carboxycholesteryl and carboxybenzyl, wherein R.sub.5 is C1 to C18 alkyl and Z.sup.- is an anion;
• and
• R.sub.3 is selected from the group consisting of C1 to C3 alkyl;
• N.sub.1 and N.sub.n+2 are each independently a nucleoside or deoxynucleoside monomer of the formula:
• ##STR11## wherein Y is selected from the group consisting of --H and --OH;
• and wherein P' is a base of a nucleic acid selected from the group consisting of adenine, thymine, cytosine, guanine, uracil, xanthine, hypoxanthine, 5-methylcytosine, 5-bromouracil, 8-azidoadenine, and 2,6-diaminopurine.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier in combination with a therapeutically effective amount of an oligonucleoside boranophosphate comprising a chain of up to 51 ribonucleosides or deoxyribonucleosides, or a pharmaceutically acceptable salt thereof, containing at least one boronated internucleotide phosphodiester linkage of the formula:

• ##STR12## wherein:
• W is selected from the group consisting of .dbd.O, .dbd.S, --OR', and --SR' wherein R' is C1 to C3 alkyl;
• X is selected from the group consisting of --BH.sub.3, --BH.sub.2 R.sub.1, --BHR.sub.1 R.sub.2 and --BR.sub.1 R.sub.2 R.sub.3 ;
• R.sub.1 is selected from the group consisting of --R.sub.4, --COOH, --COOR.sub.4, --CONHR.sub.4, --CON (R.sub.4).sub.2, --CN.sup.+ R.sub.4 Z.sup.-, --CN, carboxycholesteryl and carboxybenzyl, wherein R.sub.4 is C1 to C18 alkyl and Z.sup.- is an anion;
• R.sub.2 is selected from the group consisting of --R.sub.5, --COOH, COOR.sub.5, --CONHR.sub.5, --CON (R.sub.5).sub.2, --CN.sup.+ R.sub.5 Z.sup.-, --CN, carboxycholesteryl and carboxybenzyl, wherein R.sub.5 is C1 to C18 alkyl and Z.sup.- is an anion;
• and
• R.sub.3 is selected from the group consisting of C1 to C3 alkyl.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier in combination with an effective anti-hyperlipidemic or anti-inflammatory amount of an oligonucleoside boranophosphate comprising a chain of up to 51 ribonucleosides or deoxyribonucleosides, or a pharmaceutically acceptable salt thereof, containing at least one boronated internucleotide phosphodiester linkage of the formula:

• ##STR13## wherein:
• W is selected from the group consisting of .dbd.O, .dbd.S, --OR', and --SR' wherein R' is C1 to C3 alkyl;
• X is selected from the group consisting of --BH.sub.3, --BH.sub.2 R.sub.1, --BHR.sub.1 R.sub.2 and --BR.sub.1 R.sub.2 R.sub.3 ;
• R.sub.1 is selected from the group consisting of --R.sub.4, --COOH, --COOR.sub.4, --CONHR.sub.4, --CON(R.sub.4).sub.2, --CN.sup.+ R.sub.4 Z.sup.-, --CN, carboxycholesteryl and carboxybenzyl, wherein R.sub.4 is C1 to C18 alkyl and Z.sup.- is an anion;
• R.sub.2 is selected from the group consisting of --R.sub.5, --COOH, --COOR.sub.5, --CONHR.sub.5, --CON (R.sub.5).sub.2, --CN.sup.+ R.sub.5 Z.sup.-, --CN, carboxycholesteryl and carboxybenzyl, wherein R.sub.5 is C1 to C18 alkyl and Z.sup.- is an anion;
• and
• R.sub.3 is selected from the group consisting of C1 to C3 alkyl.

An oligonucleoside boranophosphate comprising a chain of up to three ribonucleosides or deoxyribonucleosides, or a salt thereof, containing at least one boronated internucleotide phosphodiester linkage of the formula:

• ##STR14## wherein:
• W is selected from the group consisting of .dbd.O, .dbd.S, --OR', --SR', or --OCH.sub.2 CH.sub.2 CN, wherein R' is C1 to C3 alkyl;
• X is selected from the group consisting of --BH.sub.3, --BH.sub.2 R.sub.1, --BHR.sub.1 R.sub.2 and --BR.sub.1 R.sub.2 R.sub.3 ;
• R.sub.1 is selected from the group consisting of --R.sub.4, --COOH, --COOR.sub.4 , --CONHR.sub.4, --CON (R.sub.4).sub.2, --CN.sup.+ R.sub.4 Z.sup.-, --CN, carboxycholesteryl and carboxybenzyl, wherein R.sub.4 is C1 to C18 alkyl and Z.sup.- is an anion;
• R.sub.2 is selected from the group consisting of --R.sub.5, --COOH, --COOR.sub.5, --CONHR.sub.5, --CON (R.sub.5).sub.2, --CN.sup.+ R.sub.5 Z.sup.-, --CN, carboxycholesteryl and carboxybenzyl, wherein R.sub.5 is C1 to C18 alkyl and Z.sup.- is an anion;
• and
• R.sub.3 is selected from the group consisting of C1 to C3 alkyl.

An oligonucleoside boranophosphate selected from the group consisting of thymidylyl[3'-5']-(3'-acetylthymidylyl) (borane) phosphonate methyl ester (or 3'-0[thymidylyl ]-5'0- [3'-acetylthymidylyl ]methyl phosphite-borane;

• thymidylyl [3'-5']-(3'-acetylthymidylyl) (cyanoborane)phosphonate methyl ester;
• thymidylyl [3'-5']-(3'-acetylthymidylyl ) (carbomethoxyborane) phosphonate methyl ester;
• thymidylyl [3'-5'](3'-acetylthymidylyl ) (N-ethylcarbamoylborane) phosphonate methyl ester;
• thymidylyl[3'-5']-(3'-acetylthymidylyl) (carboxyborane) phosphonate methyl ester;
• thymidylyl [3'-5']-(3'-acetylthymidylyl)(N-ethylcarbamoyl)methylborane phosphonate methyl ester;
• thymidylyl[3'-5']-thymidylyl(borane)-phosphonate ammonium salt;
• thymidylyl[3'-5']-thymidylyl(cyanoborane)-phosphonate ammonium salt;
• thymidylyl[3'-.ident.]-thymidylyl(carbomethoxy)-phosphonate ammonium salt;
• thymidylyl[3'-5']-thymidylyl(methylborane)-phosphonate ammonium salt;
• thymidylyl[3'-5']-thymidylyl(N-ethyl-carbamoyl)methylborane phosphonate ammonium salt;
• 2'deoxycytidylyl[3'-5']-2'deoxycytidylyl-(borane)phosphonate ammonium salt;
• 2'deoxycytidylyl[3'-5']-2'deoxycytidylyl-(cyanoborane)phosphonate ammonium salt;
• thymidylyl[3'-5']thymidylyl[3'-5'](3'-acetylthymidylyl) boranephosphonate dimethyl ester;
• and thymidylyl[3'-5']thymidylylboranephosphonate[3'-540 ](3'-acetylthymidylyl) cyanoboranephosphonate dimethyl ester.