# US 10,478,513 B2 · Nitroxide containing amyloid binding agents for imaging and therapeutic uses > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,478,513 B2 - Document ID: US10478513B2 - Status: Granted - Kind: B2 - Application number: 15/748,556 - Filed: 2016-08-17 - Published: 2018-08-09 - Granted: 2019-11-19 - Earliest claimed: 2015-08-18 - Assignees: The Regents of the University of Califonia - Applicants: The Regents of the University of California - Inventors: John Voss; Ruiwu Liu - Web page: https://patentgrep.com/patent/US10478513B2 ## CPC - A61K 49/20: containing free radicals {, e.g. trityl radical for overhauser} - A61K 31/015: carbocyclic - A61K 31/05: Phenols {(cannabinoids A61K31/658)} - A61K 31/353: 3,4-Dihydrobenzopyrans, e.g. chroman, catechin - A61K 31/4015: having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide - A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin - A61K 31/4184: condensed with carbocyclic rings, e.g. benzimidazoles - A61K 31/423: condensed with carbocyclic rings - A61K 31/428: condensed with carbocyclic rings - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 31/4709: Non-condensed quinolines and containing further heterocyclic rings - A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) - A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia - C07D 207/14: Nitrogen atoms not forming part of a nitro radical - C07D 207/20: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms - C07D 207/273: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms - C07D 491/052: the oxygen-containing ring being six-membered - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract The present invention provides methods of using nitroxide spin-labeled amyloid beta-binding compounds to image amyloid. The present invention also provides nitroxide spin-labeled amyloid beta-binding compounds. ## Claims ### Claim 1 A method of imaging amyloid, comprising: administering to a subject an effective amount of a compound having the structure of Formula I: X—(Y)n (I) wherein X is an amyloid beta binding compound selected from the group consisting of: wherein Ra and Rb are each independently H or C1-4 alkyl; Z is selected from the group consisting of I, 123I, 125I, 131I, Br, 76Br, 77Br, F, 18F, and —O-tosyl; and q is an integer from 2 to 5; Y is a nitroxide selected from the group consisting of: n is an integer from 1 to 3; such that the compound binds to the amyloid; and detecting the compound bound to the amyloid, thereby imaging the amyloid. ### Claim 2 (depends on 1) The method of claim 1, wherein the detecting occurs at least 60 minutes subsequent to the administering. ### Claim 3 (depends on 1) The method of claim 1, wherein the detecting comprises at least one of magnetic resonance imaging (MRI), electron paramagnetic resonance (EPR), positron emission tomography (PET), or electron spin resonance microscopy (ESRM). ### Claim 4 (depends on 1) The method of claim 1, wherein the amyloid comprises amyloid beta aggregates. ### Claim 5 (depends on 1) The method of claim 1, wherein the compound is selected from the group consisting of: ### Claim 6 (depends on 1) The method of claim 1, wherein the subject is not receiving the compound for therapeutic purposes. ### Claim 7 A compound having the formula: wherein R1 and R2 are each independently H or a nitroxide selected from the group consisting of: wherein at least one of R1 and R2 is a nitroxide. ### Claim 8 (depends on 7) The compound of claim 7, wherein the compound is selected from the group consisting of: ### Claim 9 A compound having the formula: wherein R1 and R2 are each independently H, or a nitroxide selected from the group consisting of: wherein at least one of R1 and R2 is a nitroxide. ### Claim 10 (depends on 9) The compound of claim 9, wherein the compound is selected from the group consisting of: ### Claim 11 A compound having the formula: wherein R1 is selected from the group consisting of: and R2 is selected from the group consisting of OH, OCH3, OCH2CH3, OCH2CH2F, CH3, and (OCH2CH2)3F. ### Claim 12 A compound having the formula: wherein R1 is selected from the group consisting of: and R2 is selected from the group consisting of OH, OCH3, OCH2CH3, OCH2CH2F, CH3, and (OCH2CH2)3F. ### Claim 13 A compound selected from the group consisting of: ### Claim 14 (depends on 1) A diagnostic composition for imaging amyloid, comprising a compound of claim 1. ### Claim 15 A method of treating a disorder, the method comprising administering to a subject in need thereof, a therapeutically effective amount of a Formula I: X—(Y)n (I) wherein X is an amyloid beta binding compound selected from the group consisting of: wherein Ra and Rb each independently H or C1-4 alkyl, Z is selected from the group consisting of I, 123I, 125I, 131I, Br, 76Br, 77Br, F, 18F, and O-tosyl, and q is an integer from 2 to 5; Y is a nitroxide selected from the group consisting of: and n is an integer from 1 to 3; wherein the disorder is selected from the group consisting of Alzheimer's disease, diabetes, Parkinson's disease, spongiform encephalopathy, Huntington's disease, thyroid carcinoma, atrial amyloidosis, atherosclerosis, arthritis, prolactinomas, polyneuropathy, corneal dystrophy, and cerebral amyloid angiopathy.