Claims
- 1. A method of reducing the cardiotoxicity of an anti-tumor agent administered to a human or non-human animal body, said method comprising administering to said body an anti-tumor agent and simultaneously, separately or sequentially a compound of formula I: ##STR5## or a metal chelate thereof or salt of a metal chelate thereof wherein in formula I
- each R.sup.1 independently represents hydrogen or --CH.sub.2 COR.sup.5 ;
- R.sup.5 represents hydroxy, optionally hydroxylated alkoxy, amino or alkylamido;
- each R.sup.2 independently represents a group XYR.sup.6 ;
- X represents a bond, or a C.sub.1-3 alkylene or oxoalkylene group optionally substituted by a group R.sup.7 ;
- Y represents a bond, an oxygen atom or a group NR.sup.6 ;
- R.sup.6 is a hydrogen atom, a group COOR.sup.8, an alkyl, alkenyl, cycloalkyl, aryl or aralkyl group optionally substituted by one or more groups selected from COOR.sup.8, CONR.sup.8.sub.2, NR.sup.8.sub.2, OR.sup.8, =NR.sup.8, =O, OP(O)(OR.sup.8)R.sup.7 and OSO.sub.3 M;
- R.sup.7 is hydroxy, an optionally hydroxylated, optionally alkoxylated alkyl or aminoalkyl group;
- R.sup.8 is a hydrogen atom or an optionally hydroxylated, optionally alkoxylated alkyl group;
- M is a hydrogen atom or one equivalent of a physiologically tolerable cation;
- R.sup.3 represents a C.sub.1-8 alkylene group, a 1,2-cycloalkylene group, or a 1,2-arylene group; and
- each R.sup.4 independently represents hydrogen or C.sub.1-3 alkyl.
- 2. The method as claimed in claim 1 wherein said metal chelate comprises a metal ion selected from the group consisting of alkali and alkaline earth metals and metals having an atomic number of from 22-31, 42, 44 and 58-70.
- 3. The method as claimed in claim 2 wherein said metal ion is selected from the group consisting of Na.sup.+, Mn.sup.2+, Cu.sup.+, Cu.sup.2+, Mg.sup.2+, Gd.sup.3+, Ca.sup.2+ and Zn.sup.2+.
- 4. The method as claimed in claim 1 wherein said anti-tumor agent is an anthracycline drug and/or paclitaxel.
- 5. The method as claimed in claim 4 wherein said anthracycline drug is doxorubicin or daunomycin.
- 6. The method as claimed in claim 1 wherein said chelate is manganese chelate and has a K.sub.a in the range of from 10.sup.9 to 10.sup.25.
- 7. The method as claimed in claim 6 wherein said manganese chelate has a K.sub.a in the range of from 10.sup.12 to 10.sup.22.
- 8. The method as claimed in claim 1 wherein said chelate is manganese chelate and has a K.sub.a value smaller by a factor of at least 10.sup.3 than the K.sub.a value of the corresponding iron (Fe.sup.3+) chelate.
Priority Claims (1)
Number |
Date |
Country |
Kind |
9613182 |
Jun 1997 |
GBX |
|
Parent Case Info
This application is a continuation application of international application No. PCT/GB97/01721 filed Jun. 24, 1997, of which the entire disclosure of the prior application is hereby incorporated by reference.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4138480 |
Gosalvez |
Feb 1979 |
|
Non-Patent Literature Citations (3)
Entry |
Lee et al., Diss. Abst. Int(Sci.), 46(10):3396 (1986). |
Carswell, JAMA, 248(31):814-819 (1982). |
Brurok, Invest. Radiol., 30(3):159-167 (1995). |
Continuations (1)
|
Number |
Date |
Country |
Parent |
PCTGB9701721 |
Jun 1997 |
|