Production and use of purpurins, chlorins and purpurin- and chlorin-containing compositions

Claim 2

A composition consisting essentially of a solution in a solvent of a chlorin having the structure of any of FIGS. 24-28 or a purpurin having the structure of any of FIGS. 14-18 ##STR1## wherein each of R10 through R14 is hydrogen, and each of R1 through R9 is: H or CHO, an alkyl group other than t-butyl having from 1 to 4 carbon atoms, an alkylene group having from 2 to 4 carbon atoms, a group having the formula R 2 N(R 3 ) 2 where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; R 3 is hydrogen or an alkyl group having from 1 to 2 carbon atoms and the two R 3 groups can be the same or different, a group having the formula R 2 N(R 4 ) 3 A where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; A is a physiologically acceptable anion; and R 4 is an alkyl group having from 1 to 2 carbon atoms and the three R 4 groups can be the same or different, a group having the formula R 2 OH were R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond, an amino acid moiety which is a part of an amide produced by reaction between an amine function of a naturally occurring amino acid and a carboxyl function of the purpurin or chlorin, CO 2 R', CH 2 CO 2 R' or CH 2 CH 2 CO 2 R', where R' is hydrogen or an alkyl group other than t-butyl having from 1 to 4 carbon atoms, a monoclonal antibody moiety which is attached to the purpurin or chlorin moiety through a carbonyl which is a part of an amide produced by reaction between an amine function of a monoclonal antibody and a CO 2 R' CH 2 CO 2 R' or CH 2 CH 2 CO 2 R' group of the purpurin or chlorin, and wherein the moiety is of a monoclonal antibody which selectively binds to malignant tumors, or one or both of R1 and R2 can be a bivalent aliphatic hydrocarbon radical having from 2 to 4 carbon atoms wherein both of the valences of the radical are attached to the same carbon atom thereof and to a carbon atom of the chlorin or purpurin, with the proviso that not more than one of the R1 through R9, and R14, is a group having the formula R 2 N(R 3 ) 2 , a group having the formula R 2 N(R 4 ) 3 A, an amino acid moiety or a monoclonal antibody moiety, and wherein the solution comprises an organic liquid, and is one which is physiologically acceptable and of a suitable concentration or dilutable to a suitable concentration for intravenous administration.

Claim 3

As a composition of matter, a chlorin having the structure of any of FIGS. 24, 25, 27 and 28, or a purpurin having the structure of any of FIGS. 14-18, ##STR2## wherein each of R10 through R14 is hydrogen, and each of R1 through R9 is: H or CHO, an alkyl group other than t-butyl having from 1 to 4 carbon atoms, an alkylene group having from 2 to 4 carbon atoms, a group having the formula R 2 N(R 3 ) 2 where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; R 3 is hydrogen or an alkyl group having from 1 to 2 carbon atoms and the two R 3 groups can be the same or different, a group having the formula R 2 N(R 4 ) 3 A where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; A is a physiologically acceptable anion; and R 4 is an alkyl group having from 1 to 2 carbon atoms and the three R 4 groups can be the same or different, a group having the formula R 2 OH were R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond, an amino acid moiety which is a part of an amide produced by reaction between an amine function of a naturally occurring amino acid and a carboxyl function of the purpurin or chlorin, CO 2 R', CH 2 CO 2 R' or CH 2 CH 2 CO 2 R', where R' is hydrogen or an alkyl group other than t-butyl having from 1 to 4 carbon atoms, a monoclonal antibody moiety which is attached to the purpurin or chlorin moiety through a carbonyl which is a part of an amide produced by reaction between an amine function of a monoclonal antibody and a CO 2 R' CH 2 CO 2 R' or CH 2 CH 2 CO 2 R' group of the purpurin or chlorin, and wherein the moiety is of a monoclonal antibody which selectively binds to malignant tumors, or one or both of R1 and R2 can be a bivalent aliphatic hydrocarbon radical having from 2 to 4 carbon atoms wherein both of the valences of the radical are attached to the same carbon atom thereof and to a carbon atom of the chlorin or purpurin, with the proviso that not more than one of the R1 through R9, and R14, is a group having the formula R 2 N(R 3 ) 2 , a group having the formula R 2 N(R 4 ) 3 A, an amino acid moiety or a monoclonal antibody moiety.

Claim 4

As a composition of matter, a chlorin having the structure of any of FIGS. 24, 25, 27 and 28, or a purpurin having the structure of any of FIGS. 14-18, ##STR2## wherein each of R10 through R14 is hydrogen, and each of R1 through R9 is: H or CHO, an alkyl group other than t-butyl having from 1 to 4 carbon atoms, an alkylene group having from 2 to 4 carbon atoms, a group having the formula R 2 N(R 3 ) 2 where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; R 3 is hydrogen or an alkyl group having from 1 to 2 carbon atoms and the two R 3 groups can be the same or different, a group having the formula R 2 N(R 4 ) 3 A where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; A is a physiologically acceptable anion; and R 4 is an alkyl group having from 1 to 2 carbon atoms and the three R 4 groups can be the same or different, a group having the formula R 2 OH were R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond, an amino acid moiety which is a part of an amide produced by reaction between an amine function of a naturally occurring amino acid and a carboxyl function of the purpurin or chlorin, CO 2 R', CH 2 CO 2 R' or CH 2 CH 2 CO 2 R', where R' is hydrogen or an alkyl group other than t-butyl having from 1 to 4 carbon atoms, a monoclonal antibody moiety which is attached to the purpurin or chlorin moiety through a carbonyl which is a part of an amide produced by reaction between an amine function of a monoclonal antibody and a CO 2 R' CH 2 CO 2 R' or CH 2 CH 2 CO 2 R' group of the purpurin or chlorin, and wherein the moiety is of a monoclonal antibody which selectively binds to malignant tumors, or one or both of R1 and R2 can be a bivalent aliphatic hydrocarbon radical having from 2 to 4 carbon atoms wherein both of the valences of the radical are attached to the same carbon atom thereof and to a carbon atom of the chlorin or purpurin, with the proviso that not more than one of the R1 through R9, and R14, is a group having the formula R 2 N(R 3 ) 2 , a group having the formula R 2 N(R 4 ) 3 A, an amino acid moiety or a monoclonal antibody moiety.

Claim 5

As a composition of matter, a chlorin having the structure of any of FIGS. 24-28 or a purpurin having the structure of any of FIGS. 14-18 ##STR3## wherein each of R10 through R14 is hydrogen, and each of R1 through R9 is: H or CHO, an alkyl group other than t-butyl having from 1 to 4 carbon atoms, an alkylene group having from 2 to 4 carbon atoms, a group having the formula R 2 N(R 3 ) 2 where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; R 3 is hydrogen or an alkyl group having from 1 to 2 carbon atoms and the two R 3 groups can be the same or different, a group having the formula R 2 N(R 4 ) 3 A where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; A is a physiologically acceptable anion; and R 4 is an alkyl group having from 1 to 2 carbon atoms and the three R 4 groups can be the same or different, a group having the formula R 2 OH were R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond, an amino acid moiety which is a part of an amide produced by reaction between an amine function of a naturally occurring amino acid and a carboxyl function of the purpurin or chlorin, CO 2 R', CH 2 CO 2 R' or CH 2 CH 2 CO 2 R', where R' is hydrogen or an alkyl group other than t-butyl having from 1 to 4 carbon atoms, a monoclonal antibody moiety which is attached to the purpurin or chlorin moiety through a carbonyl which is a part of an amide produced by reaction between an amine function of a monoclonal antibody and a CO 2 R' CH 2 CO 2 R' or CH 2 CH 2 CO 2 R' group of the purpurin or chlorin, and wherein the moiety is of a monoclonal antibody which selectively binds to malignant tumors, or one or both of R1 and R2 can be a bivalent aliphatic hydrocarbon radical having from 2 to 4 carbon atoms wherein both of the valences of the radical are attached to the same carbon atom thereof and to a carbon atom of the chlorin or purpurin, with the proviso that not more than one of the R1 through R9, and R14 is CHO, a group having the formula R 2 N(R 3 ) 2 , a group having the formula R 2 N(R 4 ) 3 A, an amino acid moiety or a monoclonal antibody moiety, and wherein the purpurin, chlorin or complex has a structure which is enriched in an atom which can be detected by nuclear magnetic resonance, said atom being present in the purpurin, chlorin or complex in a sufficient proportion to enable the use of nuclear magnetic resonance testing to detect small quantities of the purpurin, chlorin or complex.

Claim 6

As a composition of matter, a chlorin having the structure of any of FIGS. 24-28 or a purpurin having the structure of any of FIGS. 14-18 ##STR3## wherein each of R10 through R14 is hydrogen, and each of R1 through R9 is: H or CHO, an alkyl group other than t-butyl having from 1 to 4 carbon atoms, an alkylene group having from 2 to 4 carbon atoms, a group having the formula R 2 N(R 3 ) 2 where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; R 3 is hydrogen or an alkyl group having from 1 to 2 carbon atoms and the two R 3 groups can be the same or different, a group having the formula R 2 N(R 4 ) 3 A where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; A is a physiologically acceptable anion; and R 4 is an alkyl group having from 1 to 2 carbon atoms and the three R 4 groups can be the same or different, a group having the formula R 2 OH were R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond, an amino acid moiety which is a part of an amide produced by reaction between an amine function of a naturally occurring amino acid and a carboxyl function of the purpurin or chlorin, CO 2 R', CH 2 CO 2 R' or CH 2 CH 2 CO 2 R', where R' is hydrogen or an alkyl group other than t-butyl having from 1 to 4 carbon atoms, a monoclonal antibody moiety which is attached to the purpurin or chlorin moiety through a carbonyl which is a part of an amide produced by reaction between an amine function of a monoclonal antibody and a CO 2 R' CH 2 CO 2 R' or CH 2 CH 2 CO 2 R' group of the purpurin or chlorin, and wherein the moiety is of a monoclonal antibody which selectively binds to malignant tumors, or one or both of R1 and R2 can be a bivalent aliphatic hydrocarbon radical having from 2 to 4 carbon atoms wherein both of the valences of the radical are attached to the same carbon atom thereof and to a carbon atom of the chlorin or purpurin, with the proviso that not more than one of the R1 through R9, and R14 is CHO, a group having the formula R 2 N(R 3 ) 2 , a group having the formula R 2 N(R 4 ) 3 A, an amino acid moiety or a monoclonal antibody moiety, and wherein the purpurin, chlorin or complex has a structure which is enriched in an atom which can be detected by nuclear magnetic resonance, said atom being present in the purpurin, chlorin or complex in a sufficient proportion to enable the use of nuclear magnetic resonance testing to detect small quantities of the purpurin, chlorin or complex.

Claim 7

As a composition of matter, a chlorin having the structure of any of FIGS. 24-28 or a purpurin having the structure of any of FIGS. 14-18 ##STR4## wherein each of R10 through R14 is hydrogen, and each of R1 through R9 is: H or CHO, an alkyl group other than t-butyl having from 1 to 4 carbon atoms, an alkylene group having from 2 to 4 carbon atoms, a group having the formula R 2 N(R 3 ) 2 where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; R 3 is hydrogen or an alkyl group having from 1 to 2 carbon atoms and the two R 3 groups can be the same or different, a group having the formula R 2 N(R 4 ) 3 A where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; A is a physiologically acceptable anion; and R 4 is an alkyl group having from 1 to 2 carbon atoms and the three R 4 groups can be the same or different, a group having the formula R 2 OH were R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond, an amino acid moiety which is a part of an amide produced by reaction between an amine function of a naturally occurring amino acid and a carboxyl function of the purpurin or chlorin, CO 2 R', CH 2 CO 2 R' or CH 2 CH 2 CO 2 R', where R' is hydrogen or an alkyl group other than t-butyl having from 1 to 4 carbon atoms, a monoclonal antibody moiety which is attached to the purpurin or chlorin moiety through a carbonyl which is a part of an amide produced by reaction between an amine function of a monoclonal antibody and a CO 2 R' CH 2 CO 2 R' or CH 2 CH 2 CO 2 R' group of the purpurin or chlorin, and wherein the moiety is of a monoclonal antibody which selectively binds to malignant tumors, or one or both of R1 and R2 can be a bivalent aliphatic hydrocarbon radical having from 2 to 4 carbon atoms wherein both of the valences of the radical are attached to the same carbon atom thereof and to a carbon atom of the chlorin or purpurin, with the proviso that not more than one of the R1 through R9, and R14 is CHO, a group having the formula R 2 N(R 3 ) 2 , a group having the formula R 2 N(R 4 ) 3 A, an amino acid moiety or a monoclonal antibody moiety, and wherein the purpurin, chlorin or complex has a structure which is enriched in an atom which emits ionizing radiation, said atom being present in the purpurin, chlorin or complex in a sufficient proportion to enable the use of an instrument which detects the presence of ionizing radiation to detect small quantities of the purpurin, chlorin or complex.

Claim 8

As a composition of matter, a chlorin having the structure of any of FIGS. 24-28 or a purpurin having the structure of any of FIGS. 14-18 ##STR4## wherein each of R10 through R14 is hydrogen, and each of R1 through R9 is: H or CHO, an alkyl group other than t-butyl having from 1 to 4 carbon atoms, an alkylene group having from 2 to 4 carbon atoms, a group having the formula R 2 N(R 3 ) 2 where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; R 3 is hydrogen or an alkyl group having from 1 to 2 carbon atoms and the two R 3 groups can be the same or different, a group having the formula R 2 N(R 4 ) 3 A where R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond; A is a physiologically acceptable anion; and R 4 is an alkyl group having from 1 to 2 carbon atoms and the three R 4 groups can be the same or different, a group having the formula R 2 OH were R 2 is a bivalent aliphatic hydrocarbon radical having from 1 to 4 carbon atoms, wherein any carbon to carbon bond is either a single or a double bond, and not more than one is a double bond, an amino acid moiety which is a part of an amide produced by reaction between an amine function of a naturally occurring amino acid and a carboxyl function of the purpurin or chlorin, CO 2 R', CH 2 CO 2 R' or CH 2 CH 2 CO 2 R', where R' is hydrogen or an alkyl group other than t-butyl having from 1 to 4 carbon atoms, a monoclonal antibody moiety which is attached to the purpurin or chlorin moiety through a carbonyl which is a part of an amide produced by reaction between an amine function of a monoclonal antibody and a CO 2 R' CH 2 CO 2 R' or CH 2 CH 2 CO 2 R' group of the purpurin or chlorin, and wherein the moiety is of a monoclonal antibody which selectively binds to malignant tumors, or one or both of R1 and R2 can be a bivalent aliphatic hydrocarbon radical having from 2 to 4 carbon atoms wherein both of the valences of the radical are attached to the same carbon atom thereof and to a carbon atom of the chlorin or purpurin, with the proviso that not more than one of the R1 through R9, and R14 is CHO, a group having the formula R 2 N(R 3 ) 2 , a group having the formula R 2 N(R 4 ) 3 A, an amino acid moiety or a monoclonal antibody moiety, and wherein the purpurin, chlorin or complex has a structure which is enriched in an atom which emits ionizing radiation, said atom being present in the purpurin, chlorin or complex in a sufficient proportion to enable the use of an instrument which detects the presence of ionizing radiation to detect small quantities of the purpurin, chlorin or complex.