# US 10,478,445 B2 · Boronic acid derivatives of resveratrol for activating deacetylase enzymes > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,478,445 B2 - Document ID: US10478445B2 - Status: Granted - Kind: B2 - Application number: 14/902,783 - Filed: 2014-07-03 - Published: 2016-06-16 - Granted: 2019-11-19 - Earliest claimed: 2013-07-03 - Assignees: Georgetown University - Applicants: Georgetown University - Inventors: Insoo Bae; Yong Weon Yi; Hyo Jin Kang; Hee Jeong Kim - Web page: https://patentgrep.com/patent/US10478445B2 ## CPC - A61K 31/69: Boron compounds - A61P 35/00: Antineoplastic agents - 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 ## Abstract Disclosed herein are compounds, compositions and methods for the treatment of a disease or disorder related to activation of deacetylase enzymes. The compounds and methods are related to boronic acid derivatives of resveratrol. In some forms, the compound, compositions and methods relate to treatment of prostate cancer, colon cancer, or breast cancer, a cardiovascular disease, inflammation, obesity, diabetes, or a neurodegenerative disease. ## Claims ### Claim 1 A method comprising administering a composition to a subject, wherein the composition comprises a compound, or a pharmaceutically acceptable salt, prodrug, clathrate, tautomer or solvate thereof, wherein the compound has the structure: wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently hydrogen, hydroxyl, —B(OH)2, alkyl, alkenyl, alkynyl, halo, alkoxy, amino, alkylamino, dialkylamino, cyano, nitro, formyl, carboxyl, alkoxycarbonyl, alkoxydialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylamino carbonyl, haloalkyl, haloalkloxy, haloalkylamino, or di(haloalkyl)amino; R8 and R9 are optionally cyclized to form cycloalkyl, aryl, heteroaryl or heterocyclyl, optionally substituted with —B(OH)2, mild Lewis acid, strong acid, weak acid, alkyl, alkenyl, alkynyl, halo, alkoxy, amino, alkylamino, dialkylamino, cyano, nitro, formyl, carboxyl, alkoxycarbonyl, alkoxydialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylamino carbonyl, haloalkyl, haloalkloxy, haloalkylamino, di(haloalkyl)amino or sugars; L is or L is absent when R8 and R9 are cyclized; wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 is or includes —B(OH)2, and at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 is or includes alkoxy, alkoxydialkylamino or hydroxyl, wherein the compound is a deacetylase activator, wherein the subject is in need of treatment of a disease or condition, wherein the disease or condition is associated with expression of a deacetylase enzyme, and wherein cells of the subject express mutant p53, under-express SIRT1, have low SIRT1 activity, or combinations thereof. ### Claim 2 (depends on 1) The method of claim 1, wherein: R1, R4, R5, R6, R7, R8, R9, and R10 are independently hydrogen, —B(OH)2, alkyl, alkenyl, alkynyl, halo, alkoxy, amino, alkylamino, dialkylamino, cyano, nitro, formyl, carboxyl, alkoxycarbonyl, alkoxydialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylamino carbonyl, haloalkyl, haloalkloxy, haloalkylamino, or di(haloalkyl)amino; and R8 and R9 are optionally cyclized to form cycloalkyl, aryl, heteroaryl or heterocyclyl, optionally substituted with —B(OH)2, mild Lewis acid, strong acid, weak acid, alkyl, alkenyl, alkynyl, halo, alkoxy, amino, alkylamino, dialkylamino, cyano, nitro, formyl, carboxyl, alkoxycarbonyl, alkoxydialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylamino carbonyl, haloalkyl, haloalkloxy, haloalkylamino, di(haloalkyl)amino or sugars. ### Claim 3 (depends on 1) The method of claim 1, wherein R2 is —B(OH)2, hydroxyl or C1-C3 alkoxy. ### Claim 4 (depends on 1) The method of claim 1, wherein L is present and is: ### Claim 5 (depends on 1) The method of claim 1, wherein L is absent. ### Claim 6 (depends on 1) The method of claim 1, having the structure wherein: R12, R13, R14 and R15 are independently hydrogen, hydroxyl, —B(OH)2, alkyl, alkenyl, alkynyl, halo, alkoxy, amino, alkylamino, dialkylamino, cyano, nitro, formyl, carboxyl, alkoxycarbonyl, alkoxydialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylamino carbonyl, haloalkyl, haloalkloxy, haloalkylamino, or di(haloalkyl)amino. ### Claim 7 (depends on 6) The method of claim 6 wherein, R13 and R15 are hydrogen and R12 and R14 are independently —B(OH)2, hydroxyl, C1-C3 alkoxy or C1-C3 alkoxydialkylamino. ### Claim 8 (depends on 1) The method of claim 1, wherein the compound has the structure: ### Claim 9 (depends on 1) The method of claim 1, wherein the deacetylase enzyme is SIRT1. ### Claim 10 (depends on 1) The method of claim 1, wherein cells of the subject under-express SIRT1. ### Claim 11 (depends on 1) The method of claim 1, wherein the subject has been diagnosed with cancer, wherein cancer cells of the subject express mutant p53, under-express SIRT1, have low SIRT1 activity, or combinations thereof. ### Claim 12 (depends on 1) The method of claim 1, wherein the subject has been diagnosed with prostate cancer, colon cancer, leukemia, non-small cell lung cancer, melanoma, CNS cancer, ovarian cancer, renal cancer, or breast cancer. ### Claim 13 (depends on 12) The method of claim 12, wherein the subject is diagnosed with colon cancer or prostate cancer. ### Claim 14 (depends on 1) The method of claim 1, wherein the subject has been determined to have an increased risk of colon cancer or prostate cancer. ### Claim 15 (depends on 1) The method of claim 1, wherein the disease is prostate cancer. ### Claim 16 (depends on 1) The method of claim 1, wherein the disease or condition is cardiovascular disease, obesity, diabetes, neurodegenerative disease, Alzheimer's disease, Parkinson's disease, or inflammation. ### Claim 17 (depends on 1) The method of claim 1, wherein the disease or condition is other than cancer. ### Claim 18 (depends on 1) The method of claim 1, wherein cells of the subject have low SIRT1 activity. ### Claim 19 (depends on 1) The method of claim 1, wherein the compound has the structure: ### Claim 20 (depends on 1) The method of claim 1, wherein when R2 or R4 is —B(OH)2, R3 is not alkoxy, and wherein when R7 or R9 is —B(OH)2, R8 is not alkoxy. ### Claim 21 (depends on 20) The method of claim 20, wherein the compound has the structure: