Pharmaceutical composition containing a tetrapyrrole compound as active ingredient and process for the production of the tetrapyrrole compound

Claim 2

A process for preparing a porphyrin amino acid adduct which comprises reacting an amino dicarboxylic acid with a tetrapyrrole containing at least one carboxy group in a suitable solvent to form a compound of the structure: wherein Z is the aminodicarboxylic acid residue less the amino group and X is the tetrapyrrole residue less the carboxy group and "n" is an integer from 1 to 4 inclusive, and optionally converting the product to a salt thereof.

Claim 3

The process according to Claim 1 wherein the amino acid is an alpha aminodicarboxylic acid.

Claim 4

The process according to Claim 1 wherein the tetrapyrrole has the formula: or the corresponding di- or tetrahydrotetrapyrroles wherein provided that when R 1 , R 2 , R 3 , R 4 , R 7 and R 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; R6 and R9 , taken together are with the proviso that at least one of R 1 - R 9 includes a free carboxyl group; and optionally converting the product to a salt thereof.

Claim 5

The process according to Claim 1 wherein the tetrapyrrole has the formula: or the corresponding di- or tetrahydrotetrapyrroles wherein R 1 is methyl; R 3 is methyl R 4 is H, vinyl, ethyl, CH 2 CH 2 CO 2 H, =CHCHO; or

Claim 6

The process according to Claim 4 wherein the tetrapyrrole is a porphyrin, a chlorin or a bacteriochlorin.

Claim 7

The process according to Claim 4 wherein the amino acid is an alpha aminodicarboxylic acid, an aspartic acid or a glutamic acid.

Claim 8

The process according to Claim 1 wherein the porphyrin amino acid adduct is selected from the group monoaspartyl transmesochlorin IX, diaspartyl trans- mesochlorin IX, monoglutamyl transmesochlorin IX , diglutamyl transmesochlorin IX , monoaspartyl chlorin e 6 , t rias p ar tyl chlorin e 6 , monoglutamyl chlorin e 6 , diglutamyl protoporphyrin IX, monoaspartyl mesochlorin e 61 monoglutamyl protoporphyrin IX monoaspartyl mesoporphyrin IX, diaspartyl mesoporphyrin IX, diglutamyl mesoporphyrin IX, diaspartyl protoporphyrin IX, monoaspartylbacterio- chlorin e41 diaspartyl deuteroporphyrin IX, monoaspartyl deuteroporphyrin IX r monoglutamylbacteriois- chlor i n e 4 , d ig lu t a myl deuteroporphyrin IX, mono- or diaspartyl photoprotoporphyrin IX, mono- or diglutamyl photoprotoporphyrin IX , mono-, di-, tri- or tetraglutamyl coporphyrin III, mono- or diaspartyl hematoporphyrin IX, mono- or diglutamyl hematoporphyrin IX, mono- or diglutamyl chlorin e 41 mono- or diglutamyl. mesochlorin e 4 , mono- or diaspartyl chlorin e 4 and monoglutamyl deuteroporphyrin IX.

Claim 9

.8. A therapeutic composition for detection and/or treatment of mammalian tumors which comprises a fluorescent mono- or polyamide of an . aminodicarboxylic acid and a tetrapyrrole containing at least one carboxy group of the structure: wherein Z is the aminodicarboxylic acid residue less the amino group and X is the tetrapyrrole residue less the carboxy group and "n" is an integer from 1 to 4 inclusive, and a pharmaceutical carrier therefor.

Claim 10

.8. A therapeutic composition for detection and/or treatment of mammalian tumors which comprises a fluorescent mono- or polyamide of an . aminodicarboxylic acid and a tetrapyrrole containing at least one carboxy group of the structure: wherein Z is the aminodicarboxylic acid residue less the amino group and X is the tetrapyrrole residue less the carboxy group and "n" is an integer from 1 to 4 inclusive, and a pharmaceutical carrier therefor.

Claim 11

The therapeutic composition according to Claim 1 wherein the amino acid is an alpha aminodicarboxylic acid.

Claim 12

A therapeutic composition according to claim 8 which comprises a fluorescent mono- or polyamide of an aminodicarboxylic acid and a tetrapyrrole compound of the formula: or the corresponding di- or tetrahydrotetrapyrroles wherein provided that when R 1 , R 2 , R3, R 4 , R 7 and R 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 6 and R9, taken together are with the proviso that at least one of R 1 -R 9 includes a free carboxyl group; and salts thereof, and a pharmaceutically acceptable carrier therefor.

Claim 13

A therapeutic composition according to claim 8 which comprises a fluorescent mono- or polyamide of an aminodicarboxylic acid and fluorescent tetrapyrrole compound of the formula: or the corresponding di- or tetrahydrotetrapyrroles wherein R 1 is methyl; R 3 is methyl R 4 is H, vinyl, ethyl, CH 2 CH 2 CO 2 H, =CHCHO; or R 5 is methyl; R 6 is H , CH 2 CH 2 CO 2 H, CH 2 CH 2 CO 2 R or CO 2 H; R 8 is methyl or R 9 is H, COOH, CH 2 COOH or methyl; provided that when R 1 , R 2 , R 3 , R 4 , R 7 and R 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 6 and R 9 , taken together are with the proviso that at least one of R 1 -R 9 includes a free carboxyl group; and salts thereof, and a pharmaceutically acceptable carrier therefor.

Claim 14

The therapeutic composition according to Claim 11 wherein the tetrapyrrole is a porphyrin, a chlorin or a bacteriochlorin.

Claim 15

The therapeutic composition according to Claim 7 wherein the amino acid is an alpha aminodicarboxylic acid, an aspartic acid or an glutamic acid.

Claim 16

The therapeutic composition according to Claim 11 wherein the amide is selected from the group of Claim 7.

Claim 17

Use of a compound as described in Claims 8 to 14 for the preparation of a therapeutic composition for detecting and/or treatment of mammalian tumors.

Claim 18

A process for preparing a porphyrin amino acid adduct which comprises reacting an amino dicarboxylic acid with a tetrapyrrole containing at least one carboxy group in a suitable solvent to form a compound of the structure: wherein Z is the aminodicarboxylic acid residue less the amino group and X is the tetrapyrrole residue less the carboxy group and "n" is an integer from 1 to 4 inclusive, and optionally converting the product to a salt thereof.

Claim 19

A process for preparing a porphyrin amino acid adduct which comprises reacting an amino dicarboxylic acid with a tetrapyrrole containing at least one carboxy group in a suitable solvent to form a compound of the structure: wherein Z is the aminodicarboxylic acid residue less the amino group and X is the tetrapyrrole residue less the carboxy group and "n" is an integer from 1 to 4 inclusive, and optionally converting the product to a salt thereof.

Claim 20

The process according to Claim 1 wherein the amino acid is an alpha aminodicarboxylic acid.

Claim 21

The process according to Claim 1 wherein the tetrapyrrole has the formula: or the corresponding di- or tetrahydrotetrapyrroles wherein R 1 is methyl; R 2 is H, vinyl, ethyl, CH 2 CH 2 CO 2 H, or =CHCHO; R 3 is methyl R 4 is H, vinyl, ethyl, CH 2 CH 2 CO 2 H, =CHCHO; or R 5 is methyl; R 6 is H, CH 2 CH 2 CO 2 H, CH 2 CH 2 CO 2 R or CO 2 H; R 7 is CH 2 CH 2 CO 2 H, CH 2 CH 2 CO 2 R, or R 8 is methyl or R 9 is H, COOH, CH 2 COOH or methyl; provided that when R 1 , R 2 , R 3 , R 4 , R 7 and R 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; R6 and R 9 , taken together are with the proviso that at least one of R 1 - R includes a free carboxyl group; and optionally converting the product to a salt thereof.

Claim 22

The process according to Claim 1 wherein the tetrapyrrole has the formula: or the corresponding di- or tetrahydrotetrapyrroles wherein R 1 is methyl; R 2 is H, vinyl, ethyl, CH 2 CH 2 CO 2 H, or =CHCHO; R 3 is methyl R 4 is H, vinyl, ethyl, CH 2 CH 2 CO 2 H, =CHCHO; or

Claim 23

The process according to Claim 4 wherein the tetrapyrrole is a porphyrin, a chlorin or a bacteriochlorin.

Claim 24

The process according to Claim 4 wherein the amino acid is an alpha aminodicarboxylic acid, an aspartic acid or a glutamic acid.

Claim 25

The process according to Claim 1 wherein the porphyrin amino acid adduct is selected from the group monoaspartyl transmesochlorin IX, diaspartyl trans- mesochlorin IX, monoglutamyl transmesochlorin IX , diglutamyl transmesochlorin IX , monoaspartyl chlorin e 6 , triaspartyl chlorin e 6 , monoglutamyl chlorin e 6 , diglutamyl protoporphyrin IX , monoaspartyl mesochlorin e 61 monoglutamyl protoporphyrin IX, monoaspartyl mesoporphyrin IX, diaspartyl mesoporphyrin IX, diglutamyl mesoporphyrin IX, diaspartyl protoporphyrin IX , monoaspartylbacterio- chl or i n e41 diaspartyl deuteroporphyrin IX, monoaspartyl deuteroporphyrin IX r monoglutamylbacteriois- chlorin e 4 , diglutamyl deuteroporphyrin IX, mono- or diaspartyl photo protoporphyrin IX, mono- or diglutamyl photoprotoporphyrin IX , mono-, di-, tri- or tetraglutamyl coporphyrin III, mono- or diaspartyl hematoporphyrin IX, mono- or diglutamyl hematoporphyrin IX, mono- or diglutamyl chlorin e 41 mono- or diglutamyl mesochlorin e 4 , mono- or diaspartyl chlorin e 4 and monoglutamyl deuteroporphyrin IX.

Claim 26

Use of a compound prepared by a process according to Claims 1 to 7 for the preparation of a therapeutic composition for detecting and/or treatment of mammalian tumors.