Nucleosides and oligonucleotides containing boron clusters
First Claim
Patent Images
1. An oligonucleotide that contains at least one uncharged 3′
- ,5′
-O,O-[(carboran-1-yl-methyl)phosphonate] internucleotide linkage.
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Abstract
Carboranyl-containing nucleosides and oligonucleotides are provided for use in boron neutron capture therapy (BNCT) and for other therapeutic and diagnostic purposes.
33 Citations
26 Claims
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1. An oligonucleotide that contains at least one uncharged 3′
- ,5′
-O,O-[(carboran-1-yl-methyl)phosphonate] internucleotide linkage. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 19, 23, 24)
- ,5′
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9. An isolated oligonucleotide that contains at least one carboranyl-containing base of the formula:
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C is a carboranyl group;
R5 is lower alkyl;
G is N or CH;
M is O or S; and
Z is 0 to 5. - View Dependent Claims (10, 11, 12, 13, 20)
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14. A compound selected from the group consisting of:
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wherein R1 is alky, haloalkyl, alkenyl, alkoxyalkyl, aryl, heteroaryl, trifluoromethy, alkylary;
, arlyalkyl, or halogen;
R2 hydrogen, alkyl, acyl, sulfonate ester, a mono-, di- or triphosphate ester, trityl or monomethoxytrity, benzyl, wherein the phenyl group is optionally substituted with one or more substituents selected from the group consisting of hydroxy, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate or phosphonate, either unprotected or protected;
silyl, trialkylsilyl or diphenylmethylsilyl;
lipid;
peptide;
or cholesterol;
R3 is hydroxyl, hydrogen, halogen, —
CN, —
N3, lower alkyl, amino, alkylamino, dialkylamino, alkoxy; and
wherein R3 is in the ribosyl confirmation or down position with respect to the sugar moiety when orienting the ring such that the oxygen is in the back or the arabinosyl conformation or up with respect to the sugar moiety when orienting the ring such that the oxygen is in the back;
B represents the boron moiety of a carboranyl group W is O, S, or Se;
X is O, S, S(O), S(O)2, CH2, CHOH, CHN3 or NH;
Y is OH, SH, SeH, or halogen;
Z is O;
Base is a purine or pyrimidine;
n is 1-5; and
m is 0 or 1. - View Dependent Claims (15, 16, 17, 18, 21, 22)
wherein R1, R2, R3, B, W, X, Y, Z, m and n are as defined in claim 14.
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21. A composition comprising the compound of claim 14 in combination with a pharmaceutically acceptable carrier.
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22. A composition comprising the compound of claim 18 in combination with a pharmaceutically acceptable carrier.
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25. A method for the preparation of a nucleoside containing a 3′
- -O-[(carboran-1-yl-methyl)phosphonate] moiety comprising (i) protecting hydroxyl groups, and optionally other functional groups, on the nucleoside that are not to be phosphonated; and
(ii) reacting the protected nucleoside with a salt of O-methyl-(o-carboran-1-yl)methyl phosphonate.
- -O-[(carboran-1-yl-methyl)phosphonate] moiety comprising (i) protecting hydroxyl groups, and optionally other functional groups, on the nucleoside that are not to be phosphonated; and
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26. O-Methyl(o-carboran-1-yl)methyl phosphonate.
Specification