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US 5,405,598 AGranted
Sensitizing agents for use in boron neutron capture therapy
OwnerRaymond F. Schinazi, Dennis C. Liottainventors
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Abstract
Compounds of formula I and II ##STR1## in which B contains a carboranyl group and one of R.sub.3 and R.sub.4 is a carboranyl group or a boronic acid or ester are useful sensitizing agents for boron neutron capture therapy.
Claims19
A compound having the formula I:
- ##STR15## wherein:
- Z is OH, --OP(.dbd.O) (OH).sub.2, --OP(.dbd.O) (OH)OP(.dbd.O) (OH).sub.2, --OP(.dbd.O) (OH) OP(.dbd.O) (OH) OP(.dbd.O) (OH).sub.2, OR.sub.5 (wherein R.sub.5 is a hydroxy protecting group selected from the group consisting of tri-C.sub.1-4 -alkylsilyl, di-C.sub.1-4 -alkyl-phenylsilyl, C.sub.1-4 -alkyl-diphenylsilyl, and trityl) , --P (.dbd.O) (OH).sub.2, --P(.dbd.O) (OR.sub.6).sub.2 (wherein R.sub.6 is C.sub.1-4 -alkyl), --OR.sub.6 (wherein R.sub.6 is C.sub.1-4 -alkyl), R.sub.6 NH-- (wherein R.sub.6 is C.sub.1-4 -alkyl , R.sub.6 R.sub.6 N--, (wherein R.sub.6 is C.sub.1-4 -alkyl), R.sub.6 C (.dbd.C) O-- (wherein R.sub.6 is C.sub.1-4 -alkyl), --SH, or --SR.sub.6 (wherein R.sub.6 is C.sub.1-4 -alkyl);
- X is O, S, NR' (wherein R' is H or C.sub.1-4 -alkyl) or CHR' (wherein R' is H or C.sub.1-4 -alkyl);
- Y is O, S, NR' (wherein R' is H or C.sub.1-4 -alkyl) or CHR' (wherein R' is H or C.sub.1-4 -alkyl);
- R.sub.1 and R.sub.2 are each, independently, H, C.sub.1-4 -alkyl, --CF.sub.3, or --F;
- A is a purine or pyrimidine base selected from the group consisting of:
- ##STR16## wherein D is a carboranyl group having the formula --B.sub.10 H.sub.10 C.sub.2 R.sub.8, wherein R.sub.8 is --H, --OH, --CH.sub.2 OH, --CH.sub.2 X (wherein X is F, Cl, Br, I);
- R.sub.7 is C.sub.1-4 -alkyl or H;
- and
- W is N or CH;
- or pharmaceutically acceptable salts thereof.
8 more elements
A method of boron neutron capture therapy, comprising administering to a patient in need thereof an effective amount of a sensitizing agent which has the formula I:
- ##STR18## wherein:
- Z is OH, --OP(.dbd.O) (OH).sub.2, --OP(.dbd.O) (OH) OP(.dbd.O) (OH).sub.2, --OP(.dbd.O) (OH) OP(.dbd.O) (OH) OP(.dbd.O) (OH).sub.2, OR.sub.5 (wherein R.sub.5 is a hydroxy protecting group selected from the group consisting of tri-C.sub.1-4 -alkylsilyl, di-C.sub.1-4 -alkyl-phenylsilyl, C.sub.1-4 -alkyl-diphenylsilyl, and trityl), --P(.dbd.O) (OH).sub.2, --P(.dbd.O) (OR.sub.6).sub.2 (wherein R.sub.6 is C.sub.1-4 -alkyl), --OR.sub.6 (wherein R.sub.6 is C.sub.1-4 -alkyl) , R.sub.6 NH-- (wherein R.sub.6 is C.sub.1-4 -alkyl), R.sub.6 R.sub.6 N-- (wherein R.sub.6 is C.sub.1-4 -alkyl), R.sub.6 C(.dbd.O)O-- (wherein R.sub.6 is C.sub.1-4 -alkyl), --SH, or --SR.sub.6 (wherein R.sub.6 is C.sub.1-4 -alkyl);
- X is O, S, NR' (wherein R' is H or CC.sub.1-4 -alkyl) or CHR' (wherein R' is H or C.sub.1-4 -alkyl);
- Y is O, S, NR' (wherein R' is H or C.sub.1-4 -alkyl) or CHR' (wherein R' is H or C.sub.1-4 -alkyl);
- R.sub.1 and R.sub.2 are each, independently, H, C.sub.1-4 -alkyl, --CF.sub.3, or --F;
- A is a purine or pyrimidine base selected from the group consisting of:
- ##STR19## wherein D is a carboranyl group having the formula --B.sub.10 H.sub.10 C.sub.2 R.sub.8, wherein R.sub.8 is --H, --OH, --CH.sub.2 OH, --CH.sub.2 X (wherein X is F, Cl, Br, I);
- R.sub.7 is C.sub.1-4 -alkyl or H;
- and
- W is N or CH;
- or
- pharmaceutically acceptable salts thereof, wherein said patient is suffering from a brain glioma or a brain melanoma.
9 more elements
A pharmaceutical composition, comprising a compound having formula I:
- ##STR21## wherein:
- Z is OH, --OP(.dbd.O) (OH).sub.2, --OP(.dbd.O) (OH) OP(.dbd.O) (OH).sub.2, --OP(.dbd.O) (OH) OP(.dbd.O) (OH) OP(.dbd.O) (OH).sub.2, OR.sub.5 (wherein R.sub.5 is a hydroxy protecting group selected from the group consisting of tri-C.sub.1-4 -alkylsilyl, di-C.sub.1-4 -alkyl-phenylsilyl, C.sub.1-4 -alkyl-diphenylsilyl, and trityl), --P(.dbd.O) (OH).sub.2, --P(.dbd.O) (OR.sub.6).sub.2 (wherein R.sub.6 is C.sub.1-4 -alkyl), --OR.sub.6 (wherein R.sub.6 is C.sub.1-4 -alkyl) , R.sub.6 NH-- (wherein R.sub.6 is C.sub.1-4 -alkyl), R.sub.6 R.sub.6 N-- (wherein R.sub.6 is C.sub.1-4 -alkyl), R.sub.6 C(.dbd.O)O-- (wherein R.sub.6 is C.sub.1-4 -alkyl), --SH, or --SR.sub.6 (wherein R.sub.6 is C.sub.1-4 -alkyl);
- X is O, S, NR' (wherein R' is H or C.sub.1-4 -alkyl) or CHR' (wherein R' is H or C.sub.1-4 -alkyl);
- Y is O, S, NR' (wherein R' is H or C.sub.1-4 -alkyl) or CHR' (wherein R' is H or C.sub.1-4 -alkyl);
- R.sub.1 and R.sub.2 are each, independently, H, C.sub.1-4 -alkyl, --CF.sub.3, or --F;
- A is a purine or pyrimidine base selected from the group consisting of:
- ##STR22## wherein D is a carboranyl group having the formula --B.sub.10 H.sub.10 C.sub.2 R.sub.8, wherein R.sub.8 is --H, --OH, --CH.sub.2 OH, --CH.sub.2 X (wherein X is F, Cl, Br, I);
- R.sub.7 is C.sub.1-4 -alkyl or H;
- and
- W is N or CH;
- or acceptable salts thereof;
- and a pharmaceutically acceptable carrier.
9 more elements
Dependencies are inferred from the claim text.