Tetrapyrrole polyaminomonocarboxylic acid therapeutic agents
AssigneeNippon Petrochemicals Company, Limited
InventorsJerry C. Bommer, Bruce F. Burnham
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Abstract
This invention relates to new therapeutic compositions which are useful in photodiagnosis and phototherapy, especially in the detection and treatment of tumors and cancerous tissues in the human or animal body. The compounds of the present new therapeutic composition are mono-, di or polyamides of an amino monocarboxylic acid and a tetrapyrrole containing at least one carboxyl group of the structure ##STR1## wherein Z is the aminomonocarboxylic acid residue less the amino group, X is the tetrapyrrole residue less the carboxy group, and "n" is an integer from 1 to 4 inclusive.
Claims46
A therapeutic composition for the detection and treatment of tumors sensitive thereto comprising a therapeutically effective amount of a fluorescent mono, di or polyamide of a aminomonocarboxylic acid and a tetrapyrrole compound of the formula:
- ##STR17## or the corresponding di- or tetrahydrotetrapyrroles wherein R.sub.1 is methyl;
- ##STR18## R.sub.2 is H, vinyl, ethyl, ##STR19## acetyl, ##STR20## CH.sub.2 CH.sub.2 CO.sub.2 H, or .dbd.CHCHO;
- R.sub.3 is methyl ##STR21## R.sub.4 is H, vinyl, ethyl, ##STR22## CH.sub.2 CH.sub.2 CO.sub.2 H, .dbd.CHCHO;
- or ##STR23## R.sub.5 is methyl;
- R.sub.6 is H, CH.sub.2 CH.sub.2 CO.sub.2 H, CH.sub.2 CH.sub.2 CO.sub.2 R or CO.sub.2 H;
- R.sub.7 is CH.sub.2 CH.sub.2 CO.sub.2 H, CH.sub.2 CH.sub.2 CO.sub.2 R, or ##STR24## R.sub.8 is methyl or ##STR25## R.sub.9 is H, COOH, CH.sub.2 COOH or methyl;
- provided that when R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.7 and R.sub.8 represent two substituents or are divalent and attached to the same carbon, the respective pyrrole ring to which attached is a dihydropyrrole;
- R is lower alkyl or benzyl;
- R.sub.6 and R.sub.9, taken together are ##STR26## with the proviso that at least one of R.sub.1 -R.sub.9 includes a free carboxyl group, or salts thereof;
- and a pharmaceutically acceptable carrier therefor.
A method for detecting tumors sensitive thereto in a mammal comprising administering to said mammal a therapeutically effective amount of fluorescent mono, di or polyamide of an aminomonocarboxylic acid and a tetrapyrrole compound of the formula:
- ##STR27## or the corresponding di- or tetrahydrotetrapyrroles wherein R.sub.1 is methyl;
- ##STR28## R.sub.2 is H, vinyl, ethyl, ##STR29## acetyl, ##STR30## CH.sub.2 CH.sub.2 CO.sub.2 H, or .dbd.CHCHO;
- R.sub.3 is methyl ##STR31## R.sub.4 is H, vinyl, ethyl, ##STR32## CH.sub.2 CH.sub.2 CO.sub.2 H, .dbd.CHCHO;
- or ##STR33## R.sub.5 is methyl;
- R.sub.6 is H, CH.sub.2 CH.sub.2 CO.sub.2 H, CH.sub.2 CH.sub.2 CO.sub.2 R or CO.sub.2 H;
- R.sub.7 is CH.sub.2 CH.sub.2 CO.sub.2 H, CH.sub.2 CH.sub.2 CO.sub.2 R, or ##STR34## R.sub.8 is methyl or ##STR35## R.sub.9 is H, COOH, CH.sub.2 COOH or methyl;
- provided that when R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.7 and R.sub.8 represent two substituents or are divalent and attached to the same carbon, the respective pyrrole ring to which attached is a dihydropyrrole;
- R is lower alkyl or benzyl;
- R.sub.6 and R.sub.9, taken together are ##STR36## with the proviso that at least one of R.sub.1 -R.sub.9 includes a free carboxyl group, or salts thereof;
- applying light of sufficient wavelength to activate said mono-, di- or polyamide to the area of the mammal to be examined;
- and observing the emitted fluorescence from said tumor.
A method for treating tumors sensitive thereto in a mammal comprising administering to said mammal a therapeutically effective amount of a fluorescent mono, di or polyamide of an aminomonocarboxylic acid and a tetrapyrrole compound of the formula:
- ##STR37## or the corresponding di- or tetrahydrotetrapyrroles wherein R.sub.1 is methyl;
- ##STR38## R.sub.2 is H, vinyl, ethyl, ##STR39## acetyl, ##STR40## CH.sub.2 CH.sub.2 CO.sub.2 H, or .dbd.CHCHO;
- R.sub.3 is methyl, ##STR41## R.sub.4 is H, vinyl, ethyl, ##STR42## CH.sub.2 CH.sub.2 CO.sub.2 H, .dbd.CHCHO;
- or ##STR43## R.sub.5 is methyl;
- R.sub.6 is H, CH.sub.2 CH.sub.2 CO.sub.2 H, CH.sub.2 CH.sub.2 CO.sub.2 R or CO.sub.2 H;
- R.sub.7 is CH.sub.2 CH.sub.2 CO.sub.2 H, CH.sub.2 CH.sub.2 CO.sub.2 R, or ##STR44## R.sub.8 is methyl or ##STR45## R.sub.9 is H, COOH, CH.sub.2 COOH or methyl;
- provided that when R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.7 and R.sub.8 represent two substituents or are divalent and attached to the same carbon, the respective pyrrole ring to which attached is a dihydropyrrole;
- R is lower alkyl or benzyl;
- R.sub.6 and R.sub.9, taken together are ##STR46## with the proviso that at least one of R.sub.1 -R.sub.9 includes a free carboxyl group, or salts thereof;
- and applying light of sufficient wavelength and intensity to activate said mono-, di- or polyamide, whereby said mono-, di- or polyamide exerts a cell-killing effect on such tumor.
Dependencies are inferred from the claim text.