Boronated phosphoramidate compounds

Claim 2

A boronated compound according to the formula ##STR3## wherein: R and R 1 are each independently selected from the group consisting of hydrogen, alkyl, and alkylaryl; R 2 and R 3 are each independently selected from the group consisting of hydrogen, alkyl, alkylaryl, aryl, nucleosides and oligonucleotides; and W is polyborane or carborane, and wherein x is an integer from 1 to 20.

Claim 3

A boronated compound according to claim 1 wherein each of R 2 and R 3 is hydrogen, alkyl, alkylaryl, or aryl.

Claim 4

A boronated compound according to claim 1 wherein R 2 is hydrogen, alkyl, alkylaryl, or aryl and R 3 is a nucleoside.

Claim 5

A boronated compound according to claim 1 wherein each of R 2 and R 3 is an oligonucleotide.

Claim 6

A boronated compound according to claim 1 wherein W is a carborane.

Claim 7

A boronated compound according to claim 5 wherein said carborane is selected from the group consisting of 1,2-C 2 B 10 H 12 ; 1,7-C 2 B 10 H 12 ; 1,12-C 2 B 10 H 12 ; 1,2-C 2 B 9 H 13 ; 1,7-C 2 B 9 H 13 ; 1,2-C 2 B 9 H 12 -2 ; 1,7-C 2 B 9 H 12 -2 , 1,2-C 2 B 9 H 11 -2 ; and 1,7-C 2 B 9 H 11 -2 .

Claim 8

A boronated compound according to claim 1 wherein R 1 is hydrogen and X is an integer from 1 to 5.

Claim 9

A boronated compound according to claim 1 wherein R is hydrogen, methyl or ethyl.

Claim 10

A boronated compound according to claim 1 wherein W is a metallopolyborane or a metallocarborane.

Claim 11

A boronated compound according to the formula ##STR4## wherein: R is hydrogen or C 1 to C 5 linear alkyl; R 2 and R 3 are each independently selected from the group consisting of hydrogen, alkyl, alkylaryl, aryl, nucleosides and oligonucleotides; and W is a carborane, and wherein x is an integer from 1 to 5.

Claim 12

A boronated compound according to the formula ##STR4## wherein: R is hydrogen or C 1 to C 5 linear alkyl; R 2 and R 3 are each independently selected from the group consisting of hydrogen, alkyl, alkylaryl, aryl, nucleosides and oligonucleotides; and W is a carborane, and wherein x is an integer from 1 to 5.

Claim 13

A boronated compound according to claim 10 wherein each of R 2 and R 3 is hydrogen, alkyl, alkylaryl, or aryl.

Claim 14

A boronated compound according to claim 10 wherein R 2 is hydrogen, alkyl, alkylaryl, or aryl and R 3 is a nucleoside.

Claim 15

A boronated compound according to claim 10 wherein each of R 2 and R 3 is an oligonucleotide.

Claim 16

A boronated compound according to claim 10 wherein W is a metallocarborane.

Claim 17

A boronated compound selected from the group consisting of: (a) Dimethyl N-methyl-N-(o-carboranylmethyl) phosphoramidate; (b) Diethyl N-methyl-N-(o-carboranylmethyl) phosphoramidate; (c) Diethyl N-methyl-N(m-carboranylmethyl) phosphoramidate; (d) Dimethyl N-methyl-N-(p-carboranylmethyl) phosphoramidate; (e) Diisopropyl N-methyl-N-(p-{1-butyl} carboranylmethyl)-phosphoramidate; (f) Diethyl N-methyl-N-(o-{1-methyl} carboranylethyl)-phosphoramidate; (g) Di-n-propyl N-ethyl-N-(2-(dodecahydrododecaborato}ethyl)-phosphoramidate, disodium salt; (h) Dimethyl N-methyl-N-(2-{decahydrodecaborato}ethyl)-phosphoramidate, diammonium salt; (j) Thymidine-3'-O-[ethyl(N-methyl-N-{2-(o-carboranylethyl)})]-phosphoramidate (k) Guanosine-3'-O-[ethyl(N-methyl-N-{2-(o-carboranylethyl)})]-phosphoramidate; (l) 2'-Deoxycytidine-3'-O-[ethyl(N-methyl-N-{(2-(o-carboranylethyl)})]-phosphoramidate; (m) Thymidine-3'-O-[ethyl(N-methyl-N-{2-(1,2-dicarbonidoundecaboranyl)ethyl)})]-phosphoramidate anion; (n) Adenosine-3'-O-[ethyl(N-methyl-N-{2-(1,2-dicarbonidoundecaboranyl)ethyl)})]-phosphoramidate, tetramethylammonium salt. (o) Dodecathymidylyl-(N-methyl-N-(o-(1-methyl)carboranylethyl)-phosphoramidate; (p) Undecaguanyl-(N-methyl-N-(o-(1-methyl)carboranylethyl)-phosphoramidate; (q) Hexadecacytidylyl-(N-methyl-N-(o-(1-methyl)carboranylethyl)-phosphoramidate; (r) ApTpCpGpTpTpTpAp * T where p=normal phosphate and p * =N-ethyl-N-(1,7-dicarboclosododecaboranyl)methylphosphoramidate (SEQ ID No. 1); (s) Tp * Ap * Tp * Gp * Cp * Ap * Tp * Gp * Ap * Ap * Cp * Cp * Gp * Tp * T where p * =N-butyl-N-(6-[{1-propyl}1,12-dicarboclosododecaboranyl])hexyl-phosphoramidate (SEQ ID No. 2); (t) Tp'Tp'Ap'Ap'Ap'Tp * Tp * Tp * Ap * Ap * where p'=thiophosphate, p * =N-methyl-N-[2-(o-(1-methyl) carboranylethyl)] phosphoramidate (SEQ ID No. 3); (u) Cp * Cp * Cp * Gp * Gp * Gp * CpCpCpGpGpGp where p=normal phosphate and p * =N-ethyl-N-(1,7-dicarboclosododecaboranyl)methyl-phosphoramidate (SEQ ID No. 4); (v) Tp'Tp'Tp'Tp'Tp'Tp'Tp'Tp * Tp * Tp * Tp * Tp * T where p'=N-methyl-N-{2-(1,2-dicarbonidoundecaboranyl) ethyl)})]-phosphoramidate, ammonium salt and p * =N-butyl-N-(6-[{1-propyl} 1,12-dicarboclosododecaboranyl])hexyl-phosphoramidate (SEQ ID No. 5); and (w) Ap'Tp'Cp'Gp'Tp'Gp'Ap * Tp * Ap * Cp * Gp * T where p'=N-ethyl-N-(1,7-dicarboclosododecaboranyl)methyl-phosphoramidate and p * =N-ethyl-N-(2-{dodecahydrododecaborato}ethyl)-phosphoramidate, disodium salt (SEQ ID No. 6).

Claim 18

A boronated compound selected from the group consisting of: (a) Dimethyl N-methyl-N-(o-carboranylmethyl) phosphoramidate; (b) Diethyl N-methyl-N-(o-carboranylmethyl) phosphoramidate; (c) Diethyl N-methyl-N(m-carboranylmethyl) phosphoramidate; (d) Dimethyl N-methyl-N-(p-carboranylmethyl) phosphoramidate; (e) Diisopropyl N-methyl-N-(p-{1-butyl} carboranylmethyl)-phosphoramidate; (f) Diethyl N-methyl-N-(o-{1-methyl} carboranylethyl)-phosphoramidate; (g) Di-n-propyl N-ethyl-N-(2-(dodecahydrododecaborato}ethyl)-phosphoramidate, disodium salt; (h) Dimethyl N-methyl-N-(2-{decahydrodecaborato}ethyl)-phosphoramidate, diammonium salt; (j) Thymidine-3'-O-[ethyl(N-methyl-N-{2-(o-carboranylethyl)})]-phosphoramidate (k) Guanosine-3'-O-[ethyl(N-methyl-N-{2-(o-carboranylethyl)})]-phosphoramidate; (l) 2'-Deoxycytidine-3'-O-[ethyl(N-methyl-N-{(2-(o-carboranylethyl)})]-phosphoramidate; (m) Thymidine-3'-O-[ethyl(N-methyl-N-{2-(1,2-dicarbonidoundecaboranyl)ethyl)})]-phosphoramidate anion; (n) Adenosine-3'-O-[ethyl(N-methyl-N-{2-(1,2-dicarbonidoundecaboranyl)ethyl)})]-phosphoramidate, tetramethylammonium salt. (o) Dodecathymidylyl-(N-methyl-N-(o-(1-methyl)carboranylethyl)-phosphoramidate; (p) Undecaguanyl-(N-methyl-N-(o-(1-methyl)carboranylethyl)-phosphoramidate; (q) Hexadecacytidylyl-(N-methyl-N-(o-(1-methyl)carboranylethyl)-phosphoramidate; (r) ApTpCpGpTpTpTpAp * T where p=normal phosphate and p * =N-ethyl-N-(1,7-dicarboclosododecaboranyl)methylphosphoramidate (SEQ ID No. 1); (s) Tp * Ap * Tp * Gp * Cp * Ap * Tp * Gp * Ap * Ap * Cp * Cp * Gp * Tp * T where p * =N-butyl-N-(6-[{1-propyl}1,12-dicarboclosododecaboranyl])hexyl-phosphoramidate (SEQ ID No. 2); (t) Tp'Tp'Ap'Ap'Ap'Tp * Tp * Tp * Ap * Ap * where p'=thiophosphate, p * =N-methyl-N-[2-(o-(1-methyl) carboranylethyl)] phosphoramidate (SEQ ID No. 3); (u) Cp * Cp * Cp * Gp * Gp * Gp * CpCpCpGpGpGp where p=normal phosphate and p * =N-ethyl-N-(1,7-dicarboclosododecaboranyl)methyl-phosphoramidate (SEQ ID No. 4); (v) Tp'Tp'Tp'Tp'Tp'Tp'Tp'Tp * Tp * Tp * Tp * Tp * T where p'=N-methyl-N-{2-(1,2-dicarbonidoundecaboranyl) ethyl)})]-phosphoramidate, ammonium salt and p * =N-butyl-N-(6-[{1-propyl} 1,12-dicarboclosododecaboranyl])hexyl-phosphoramidate (SEQ ID No. 5); and (w) Ap'Tp'Cp'Gp'Tp'Gp'Ap * Tp * Ap * Cp * Gp * T where p'=N-ethyl-N-(1,7-dicarboclosododecaboranyl)methyl-phosphoramidate and p * =N-ethyl-N-(2-{dodecahydrododecaborato}ethyl)-phosphoramidate, disodium salt (SEQ ID No. 6).

Claim 19

A boronated compound according to claim 15 selected from the group consisting of: (a) Dimethyl N-methyl-N-(o-carboranylmethyl) phosphoramidate; (b) Diethyl N-methyl-N-(o-carboranylmethyl) phosphoramidate; (c) Diethyl N-methyl-N(m-carboranylmethyl) phosphoramidate; (d) Dimethyl N-methyl-N-(p-carboranylmethyl) phosphoramidate; (e) Diisopropyl N-methyl-N-(p-{1-butyl} carboranylmethyl)-phosphoramidate; (f) Diethyl N-methyl-N-(o-{1-methyl} carboranylethyl)-phosphoramidate; (g) Di-n-propyl N-ethyl-N-(2-{dodecahydrododecaborato}ethyl)-phosphoramidate, disodium salt; and (h) Dimethyl N-methyl-N-(2-{decahydrodecaborato}ethyl)-phosphoramidate, diammonium salt;

Claim 20

A boronated compound according to claim 15 selected from the group consisting of: (j) Thymidine-3'-O-[ethyl(N-methyl-N-{2-(o-carboranylethyl)})]-phosphoramidate; (k) Guanosine-3'-O-[ethyl(N-methyl-N-{2-(o-carboranylethyl)})]-phosphoramidate; (l) 2'-Deoxycytidine-3'-O-[ethyl(N-methyl-N-{2-(o-carboranylethyl)})]-phosphoramidate; (m) Thymidine-3'-O-[ethyl(N-methyl-N-{2-(1,2-dicarbonidoundecaboranyl)ethyl)})]-phosphoramidate anion; (n) Adenosine-3'-O-[ethyl(N-methyl-N-{2-(1,2-dicarbonidoundecaboranyl)ethyl)})]-phosphoramidate, tetramethylammonium salt; (o) Dodecathymidylyl-(N-methyl-N-(o-(1-methyl)carboranylethyl)-phosphoramidate; (p) Undecaguanyl-(N-methyl-N-(o-(1-methyl)carboranylethyl)-phosphoramidate; and (q) Hexadecacytidylyl-(N-methyl-N-(o-(1-methyl)carboranylethyl)-phosphoramidate.

Claim 21

A boronated compound according to claim 15 selected from the group consisting of: (r) ApTpCpGpTpTpTpAp * T where p=normal phosphate and p * =N-ethyl-N-(1,7-dicarboclosododecaboranyl)methylphosphoramidate (SEQ ID No. 1); (s) Tp * Ap * Tp * Gp * Cp * Ap * Tp * Gp * Ap * Ap * Cp * Cp * Gp * Tp * T where p * =N-butyl-N-(6-[{1-propyl}1,12-dicarboclosododecaboranyl])hexyl-phosphoramidate (SEQ ID No. 2); (t) Tp'Tp'Ap'Ap'Ap'Tp * Tp * Tp * Ap * Ap * where p'=thiophosphate, p * =N-methyl-N-[2-(o-(1-methyl) carboranylethyl)] phosphoramidate (SEQ ID No. 3); (u) Cp * Cp * Cp * Gp * Gp * Gp * CpCpCpGpGpGp where p=normal phosphate and p * =N-ethyl-N-(1,7-dicarboclosododecaboranyl)methyl-phosphoramidate (SEQ ID No. 4); (v) Tp'Tp'Tp'Tp'Tp'Tp'Tp'Tp * Tp * Tp * Tp * Tp * T where p'=N-methyl-N-{2-(1,2-dicarbonidoundecaboranyl) ethyl)})]-phosphoramidate, ammonium salt and p * =N-butyl-N-(6-[{1-propyl} 1,12-dicarboclosododecaboranyl])hexyl-phosphoramidate (SEQ ID No. 5); and (w) Ap'Tp'Cp'Gp'Tp'Gp'Ap * Tp * Ap * Cp * Gp * T where p'=N-ethyl-N-(1,7-dicarboclosododecaboranyl)methyl-phosphoramidate and p * =N-ethyl-N-(2-(dodecahydrododecaborato}ethyl)-phosphoramidate, disodium salt (SEQ ID No. 6).