Abstract: Methods of modifying polypyrrolic macrocycles by use of a 1,3-dipolar cycloaddition are described. The methods may be used to produce compounds for further derivatization to produce photosensitizing agents of interest.

Abstract: The invention is generally related to the field of photodynamic therapy by use of photosensitizers and stabilized formulations of the photosensitizers. These formulations may be used to deliver a photosensitizer as a pharmaceutical, agricultural, or industrial agent. The photosensitizer containing formulations and compositions of the invention comprise one or more block copolymers. Furthermore, the invention relates to processes for the production of, and application of, said formulations and compositions as photosensitizer drug delivery systems.

Abstract: A method for the separation of benzoporphyrin derivative mono and diacid (BPD-MA, BPD-DA) enantiomers by Laser-Induced Fluorescence Capillary Electrophoresis has been developed. The limits of detection are 2.06×10−6 M, and the relative standard deviation for the separation was 2.90% to 4.64%. The BPD enantiomers can be quantitatively determined in the range of 10−2 to 10−5 mg mL−1. In comparison with HPLC, CE has better resolution and efficiency. This separation method was successfully applied to the BPD enantiomers obtained from a matrix of bovine serum and from liposomally formulated material as well as from studies with rat, dog and human microsomes.

Abstract: The invention is generally related to the field of formulating medicaments in association with a solid support. Such formulations comprising photosensitizers, and their use in photodynamic therapy, are also provided. Methods for the production of the medicament formulations are also disclosed.

Abstract: A method for the separation of benzoporphyrin derivative mono and diacid (BPD-MA, BPD-DA) enantiomers by Laser-Induced Fluorescence Capillary Electrophoresis has been developed. The limits of detection are 2.06×10−6 M, and the relative standard deviation for the separation was 2.90% to 4.64%. The BPD enantiomers can be quantitatively determined in the range of 10−2 to 10−5 mg mL−1. In comparison with HPLC, CE has better resolution and efficiency. This separation method was successfully applied to the BPD enantiomers obtained from a matrix of bovine serum and from liposomally formulated material as well as from studies with rat, dog and human microsomes.

Abstract: New compounds useful in photodynamic therapy are of the formula ##STR1## and their 1,4-diene isomers and the metallated and/or labeled and/or conjugated forms thereofwherein each R.sup.1 is independently alkyl (1-6C);each n is independently an integer of 0-6; andR.sup.2 is vinyl or a derivative form thereof.

Abstract: The present invention provides for novel therapeutic macrocycle compounds useful in photodynamic therapy that are based on the chlorin ring system. The macrocycle compounds have, in many cases, wavelengths of activation at about 670 nm, characteristics of chlorins, and are stabilized against oxidation by the attachment to the chlorin ring of a structure that comprises one or more exocyclic rings that contribute at least one nitrogen atom. Protonation or covalent modification of this nitrogen atom, or other covalent modification of the one or more exocyclic rings permits optimization of pharmacalogically relevant properties including, for example, solubility.

Abstract: The invention provides for tripyrrane compounds of the formula ##STR1## wherein: each Q represents, typically, an alkyl group, cycloalkyl group, aryl group, or a heteroaryl group; and each R represents hydrogen, an alkyl group, alcohol group, or a carbonyl-containing group.Additionally, there are described methods to prepare such compounds, for example, comprising the steps of:(a) reacting a compound of the formula:Q--CHO or Q--CH(OS)(OS')wherein S and S' are independently lower alkyl, an aryl group containing from 5 to 14 ring atoms, and --(CH.sub.2).sub.n -- where n =2-4;with a stoichiometric excess of a pyrrole having the formula: ##STR2## in the presence of a catalytic amount of an acid; (b) removing the unreacted pyrrole or any other solvents used in (a) by evaporation to form a residue; and(c) treating the residue to remove high molecular weight polymeric materials and the corresponding dipyrromethane by-product, leaving the desired compound.

Abstract: New compounds expanding the repertoire of compounds useful in photodynamic therapy are described. Monohydrobenzoporphyrins can be obtained in the triacid form or as esters with heteroatom-substituted alcohols, or as amides.

Abstract: This invention is a process for the use of a combination of ionizing radiation in conjunction with certain benzoporphyrin derivative compounds (BPD), preferably the compound benzoporphyrin derivative-monoacid ring-A (BPD-MA), to mediate the destruction of diseased or unwanted cells or tissues. Specifically, the invention is a method in which the sensitizer compounds are administered either systemically or locally to the diseased or unwanted tissue and irradiated with ionizing radiation (such as might be produced by a .sup.60 Co or x-ray source). The treatment with benzoporphyrin derivative compounds appears to sensitize the target cells or tissues in that those cells do not readily recover from irradiation exposure. In addition, the process may be used to lower the effective amount of radiation applied to a particular tissue target.

Abstract: New compounds useful in photodynamic therapy are of the formula ##STR1## and their 1,4-diene isomers and the metallated and/or labeled and/or conjugated forms thereofwherein each R.sup.1 is independently alkyl (1-6C);each n is independently an integer of 0-6; andR.sup.2 is vinyl or a derivative form thereof.

Abstract: The invention provides for tripyrrane compounds of the formula ##STR1## wherein: each Q represents, typically, an alkyl group, cycloalkyl group, aryl group, or a heteroaryl group; and each R represents hydrogen, an alkyl group, alcohol group, or a carbonyl-containing group. Additionally, there are described methods to prepare such compounds, for example, comprising the steps of:(a) reacting a compound of the formula:Q--CHO or Q--CH(OS)(OS')wherein S and S' are independently lower alkyl, an aryl group containing from 5 to 14 ring atoms, and --(CH.sub.2).sub.n -- where n=2-4;with a stoichiometric excess of a pyrrole having the formula: ##STR2## in the presence of a catalytic amount of an acid; (b) removing the unreacted pyrrole or any other solvents used in (a) by evaporation to form a residue; and(c) treating the residue to remove high molecular weight polymeric materials and the corresponding dipyrromethane by-product, leaving the desired compound.

Abstract: A compound of Formula I: ##STR1## wherein: Q represents identical alkyl groups, cycloalkyl groups having from 5 to 7 ring atoms, or aryl or heteroaryl groups having from 5 to 12 ring atoms andR represents identical hydrogen, alkyl, alcohol or carbonyl-containing groups;or a composition containing from 5 to 100 mole % by weight of the compound of Formula I. A novel method for synthesizing the compound of Formula I comprises the steps of: (a) reacting a compound of the formula:Q--CHO or Q--CH(OS)(OS')wherein Q is as defined above andS and S' are independently lower alkyl, an aryl group containing from 5 to 14 ring atoms, and --(CH.sub.2).sub.n -- where n=2-4, with an excess amount of a pyrrole in the presence of a catalytic amount of a strong Lewis or Bronsted acid;(b) removing any unreacted pyrrole or other solvents used by evaporation;(c) removing polymeric materials and removing the corresponding dipyrromethane by-product, leaving the compound of Formula I.

Abstract: New compounds expanding the repertoire of compounds useful in photodynamic therapy are described. Monohydrobenzoporphyrins can be obtained in the triacid form or as esters with heteroatom-substituted alcohols, or as amides.

Abstract: A .beta.,.beta.'-dihydroxy meso-substituted chlorin, bacteriochlorin or isobacteriochlorin compound having the formula (I) or (II): ##STR1## wherein M is a metal. A novel method for synthesizing the compound of formula (I) or (II) comprises the steps of:a. osmylating a .beta...beta.'-unsubstituted, meso-substituted porphyrin to form an osmate ester at the .beta.,.beta.'-position, andb. reducing the osmate ester to form the corresponding .beta.,.beta.'-dihydroxy meso-substituted chlorin, bacteriochlorin or isobacteriochlorin of formula (I) or (II).

Abstract: A compound of Formula I: ##STR1## wherein: Q represents identical alkyl groups, cycloalkyl groups having from 5 to 7 ring atoms, or aryl or heteroaryl groups having from 5 to 12 ring atoms andR represents identical hydrogen, alkyl, alcohol or carbonyl-containing groups;or a composition containing from 5 to 100 mole % by weight of the compound of Formula I. A novel method for synthesizing the compound of Formula I comprises the steps of:(a) reacting a compound of the formula:Q--CHO or Q--CH(OS)(OS')wherein Q is as defined above and S and S' are independently lower alkyl, an aryl group containing from 5 to 14 ring atoms, and --(CH.sub.2).sub.n -- where n=2-4, with an excess amount of a pyrrole in the presence of a catalytic amount of a strong Lewis or Bronsted acid;(b) removing any unreacted pyrrole or other solvents used by evaporation;(c) removing polymeric materials and removing the corresponding dipyrromethane by-product, leaving the compound of Formula I.

Abstract: A novel 5,15-diarylbenzochlorin-7-one compound having the formula (I) or (II): ##STR1## wherein M is a metal. A novel method for synthesizing the compound of formula (I) comprises the steps of:a. cyclizing a meso-(formylvinyl) 5,15-diarylporphyrin to form a cyclization reaction mixture, andb. oxidizing said reaction mixture to form the 5,15-diarylbenzochlorin-7-one of formula (I).A novel method for synthesizing the compound of formula (II) comprises the cyclizing and oxidizing steps listed above and, either prior to or after the oxidizing step, adding the step of demetallating the compound.

Abstract: Compounds of the formula ##STR1## and the metalated forms and salts thereof; wherein n is an integer of 1-4; andwherein each P.sub.i is independently a pyrrole residue of the formula ##STR2## wherein each R.sub.ia and R.sub.ib is independently a noninterfering substituent, andwherein each Z.sub.i is independently a covalent bond; or isa meso bridging group of the formula ##STR3## or is an N-meso bridging group of the formula.dbd.N--.revreaction.--N.dbd.; or isa CC linkage of the formula ##STR4## or is a CNCCNC linkage of the formula ##STR5## wherein each R.sub.ic, R.sub.id, R.sub.ie, R.sub.if and R.sub.ig is independently a noninterfering substituent; or isa CNC linkage of the formula--CH.dbd.N--CH.dbd..revreaction..dbd.CH--N.dbd.CH--wherein at least one Z.sub.i is said CNC linkage, are disclosed. These compounds are useful in photodynamic therapy and diagnosis. The metalated forms when the metal is paramagnetic are useful as MRI contrast agents.

Abstract: A meso-monoiodo-substituted tetramacrocyclic compound having the formula (I): ##STR1## wherein: each of A through D is independently a 5-membered, nitrogen-containing ring having the members necessary to complete a porphyrin, chlorin, bacteriochlorin or isobacteriochlorin nucleus;R.sub.1 through R.sub.8 are independently a hydrogen atom, a lower alkyl group, a lower alkyl carboxylic acid or acid ester group, keto, hydroxy, nitro, amino, or a group that, taken together with another ring, ring substituent or meso-substituent, forms a fused 5- or 6-membered ring; andeach of S.sup.1 through S.sup.3 is H, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, a substituted or unsubstituted aromatic ring, or a substituted or unsubstituted heterocyclic ring. A method for synthesizing the compound comprises the step of iodinating a corresponding unhalogenated, de-metallated tetramacrocyclic compound, followed by metallating.

Abstract: A novel 5,15-diarylbenzochlorin-7-one compound having the formula (I) or (II): ##STR1## wherein M is a metal. A novel method for synthesizing the compound of formula (I) comprises the steps of:a. cyclizing a meso-(formylvinyl) 5,15-diarylporphyrin to form a cyclization reaction mixture, andb. oxidizing said reaction mixture to form the 5,15-diarylbenzochlorin-7-one of formula (I).A novel method for synthesizing the compound of formula (II) comprises the cyclizing and oxidizing steps listed above and, either prior to or after the oxidizing step, adding the step of demetallating the compound.