Diaza heterocyclic compounds for phototherapy
View Patent ↗The invention relates generally to optical agents, including phototherapeutic agents, for biomedical applications, including phototherapy. The invention includes optical agents, and related therapeutic methods, comprising alicyclic diaza compounds, including 1,2 diaza heterocyclic compounds, having a photolabile N—N bond directly or indirectly linked to at least one carbocyclic aromatic and/or heterocyclic aromatic group. In some embodiments, for example, the invention provides alicyclic diaza compounds for phototherapeutic methods having a photolabile N—N bond that undergoes photoactivated cleavage to produce reactive species, such as radicals, ions, etc., that achieve a desired therapeutic effect, such as selective and/or localized tissue damage and/or cell death.
1. A method of treating cancer, a cancer-associated disorder, inflammation or an inflammation -associated disorder, the method comprising: (i) administering to a patient a therapeutically effective amount of a phototherapeutic agent to a target tissue of said patient, the phototherapeutic agent comprising a compound being of the formula (FX38); and (ii) exposing the phototherapeutic agent administered to the patient at the target tissue to electromagnetic radiation having wavelengths selected over the range of 350 nm and 1300 nm sufficient to result in injury or death to cells at the target tissue; wherein
each of R 1 and R 6 is independently hydrogen, C 1 -C 20 alkyl, C 3 -C 20 cycloalkyl, C 5 -C 30 aryl, C 5 -C 30 heteroaryl, C 1 -C 20 acyl, C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, C 5 -C 20 alkylaryl, —(CHOH) m R 34 , —(CH 2 CH 2 O) m R 35 , —CH(R 36 )CO 2 H, or —CH(R 37 )NH 2
each of R 34 and R 35 is independently hydrogen or C 1 -C 10 alkyl;
R 37 is independently a side chain residue of a natural α-amino acid and m is independently an integer selected from the range of 1 to 100
wherein the exposing cleaves the N—N bond forming two N radicals; and wherein the method is a Type 1 phototherapy procedure.
2. The method of claim 1 , wherein at least one of R 1 and R 6 is a dye that is excited upon exposure to electromagnetic radiation having wavelengths selected over the range of 350 nm to 1300 nanometers; wherein said dye selected from the group consisting of a pyrazine, a thiazole, a phenylxanthene, a phenothiazine, a phenoselenazine, a cyanine, an indocyanine, a squaraine, a dipyrrolo pyrimidone, an anthraquinone, a tetracene, a quinoline, an acridine, an acridone, a phenanthridine, an azo dye, a rhodamine, a phenoxazine, an azulene, an azaazulene, a triphenyl methane dye, an indole, a benzoindole, an indocarbocyanine, a Nile Red dye, or a benzoindocarbocyanine.
3. The method of claim 1 , wherein the compound is of the formula FX(36):
4. The method of claim 1 , wherein the target tissue is a colon, prostate, gastric, esophageal, uterine, endometrial, pancreatic, breast, cervical, brain, skin, gallbladder, lung, throat, kidney, testicular, prostate, gastric, or ovary tissue.
5. The method of claim 1 , wherein the target tissue is cancerous tissue, or a tumor.
6. The method of claim 1 , wherein said electromagnetic radiation has wavelengths selected over the range of 350 nm to about 900 nm.
7. The method of claim 1 , wherein R 1 and R 6 are each t-Bu or H.