# US 5,705,521 A · Use of allosteric hemoglobin modifiers in combination with radiation therapy to treat carcinogenic tumors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,705,521 A - Document ID: US5705521A - Status: Granted - Kind: A - Application number: 08/482,808 - Filed: 1995-06-07 - Granted: 1998-01-06 - Earliest claimed: 1990-02-12 - Assignees: Center for Innovative Technology - Inventors: Donald J. Abraham - Web page: https://patentgrep.com/patent/US5705521A ## CPC - C07D 209/48: with oxygen atoms in positions 1 and 3, e.g. phthalimide - A61K 31/195: having an amino group - A61K 31/215: of carboxylic acids - A61K 31/325: Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof (thiurams A61K31/145) - A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - C07C 233/29: having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings - C07C 233/73: of a carbon skeleton containing six-membered aromatic rings - C07C 235/38: having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring - C07C 235/46: having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms - C07C 271/58: with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring - C07C 2602/08: the other ring being five-membered, e.g. indane - C07C 2603/74: Adamantanes - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS ## Abstract A family of compounds has been found to be useful for right-shifting hemoglobin towards a low oxygen affinity state. The effect has particular application in radiation oncology applications. The compounds are capable of acting on hemoglobin in whole blood. ## Claims ### Claim 1 A method of treating a carcinogenic tumor in a patient, comprising the steps of: administering to a patient a sufficient quantity of an allosteric effector compound to oxygenate a carcinogenic tumor in said patient, said allosteric effector compound having the general structural formula: R.sub.1 --(A)--R.sub.2 where R.sub.1 and R.sub.2 each are a substituted or unsubstituted aromatic or heteroaromatic compound, or a substituted or unsubstituted alkyl or heteroalkyl ring compound, or a substituted or unsubstituted phthalimide compound, and where R.sub.1 and R.sub.2 may be the same or different, where A is a chemical bridge which includes two to four moieties bonded together between R.sub.1 and R.sub.2, wherein said chemical moieties in A are selected from the group consisting of CO, O, S, SO.sub.2, NH, NR.sub.3 where R.sub.3 is a C.sub.1-4 alkyl group, NR.sub.4 where R.sub.4 includes two carbonyls as part of a phthalimide compound formed with R.sub.1 and R.sub.2, CH.sub.2, CH, and C, with the caveat that, except in the case where A contains identical CH and C moieties positioned adjacent one another to form an alkene or alkyne, the chemical moieties in A are each different from one another, and wherein at least on of R.sub.1 and R.sub.2 is substituted with a compound having the chemical formula: ##STR8## where n is zero to five, where R.sub.5 and R.sub.6 are selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C.sub.1-12 alkyl groups, carboxylic acid and ester, substituted or unsubstituted aromatic or heteroaromatic groups, and these moieties may be the same or different, or alkyl moieties of part of an aliphatic ring connecting R.sub.5 and R.sub.6, and where R.sub.7 is a hydrogen, halogen, salt cation, metal, or substituted or unsubstituted C.sub.1-6 alkyl group; and subjecting said carcinogenic tumor to radiation. ### Claim 2 (depends on 1) The method of claim 1 wherein said step of administering is performed intravenously. ### Claim 3 (depends on 1) The method of claim 1 wherein said allosteric effector compound is 2-›4-((((3,5-dimethylphenyl)amino)carbonyl)methyl)phenoxy!-2-methylpropion ic acid. ### Claim 4 (depends on 1) A method as recited in claim 1 wherein said carcinogenic tumor is a tumor of the connective tissue group. ### Claim 5 (depends on 4) A method as recited in claim 4 wherein said carcinogenic tumor is a tumor of the connective tissue group. ### Claim 6 A method of treating a carcinogenic tumor in a patient by increasing tumor oxygenation, comprising the step of: administering to a patient a sufficient quantity of an allosteric effector compound to oxygenate a carcinogenic tumor in said patient, said allosteric effector compound having the general structural formula: R.sub.1 --(A)--R.sub.2 where R.sub.1 and R.sub.2 each are a substituted or unsubstituted aromatic or heteroaromatic compound, or a substituted or unsubstituted alkyl or heteroalkyl ring compound, or a substituted or unsubstituted phthalimide compound, and where R.sub.1 and R.sub.2 may be the same or different, where A is a chemical bridge which includes two to four moieties bonded together between R.sub.1 and R.sub.2, wherein said chemical moieties in A are selected from the group consisting of CO, O, S, SO.sub.2, NH, NR.sub.3 where R.sub.3 is a C.sub.1-6 alkyl group, NR.sub.4 where R.sub.4 includes two carbonyls as part of a phthalimide compound formed with R.sub.1 and R.sub.2, CH.sub.2, CH, and C, with the caveat that, except in the case where A contains identical CH and C moieties positioned adjacent one another to form an alkene or alkyne, the chemical moieties in A are each different from one another, and wherein at least on of R.sub.1 and R.sub.2 is substituted with a compound having the chemical formula: ##STR9## where n is zero to five, where R.sub.5 and R.sub.6 are selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C.sub.1-12 alkyl groups, carboxylic acid and ester, substituted or unsubstituted aromatic or heteroaromatic groups, and these moieties may be the same or different, or alkyl moieties of part of an aliphatic ring connecting R.sub.5 and R.sub.6, and where R.sub.7 is a hydrogen, halogen, salt cation, metal, or substituted or unsubstituted C.sub.1-6 alkyl group. ### Claim 7 (depends on 6) The method of claim 6 wherein said step of administering is performed intravenously. ### Claim 8 (depends on 6) The method of claim 6 wherein said allosteric effector compound is 2-›4-((((3,5-dimethylphenyl)amino)carbonyl)methyl)phenoxy!-2-methylpropion ic acid.