Jonathan D Abramson

US Patent:

8323977, Dec 4, 2012

Filed:

Aug 9, 2011

Appl. No.:

13/206364

Inventors:

Jonathan J. Abramson - Beaverton OR, US
Benjamin S. Marinov - Portland OR, US

Assignee:

State of Oregon acting by and through the State Board of Higher Education on behalf of Portland State University - Portland OR

International Classification:

G01N 31/00

US Classification:

436 2, 436172, 436164

Abstract:

A method for identifying the redox activity of a subject compound is disclosed. The method can be performed aerobically and can include forming a mixture comprising a free-radical precursor and a compound to be tested, and converting the free-radical precursor into a free-radical anion and a free-radical cation. After the free radical cation and the free radical anion have been formed, the relative redox activity of the subject compound may cause a difference in the rate of photo-bleaching of the mixture and/or the rate of superoxide generation. These differences can be quantified and used to identify the redox activity of the subject compound. This sensitive technique for measuring redox activity can be used to screen compounds for various biological applications. Drugs also can be developed based on the relationship between redox activity and biological activity for particular biological applications.

US Patent:

20060188997, Aug 24, 2006

Filed:

Jan 27, 2006

Appl. No.:

11/340938

Inventors:

Jonathan Abramson - Beaverton OR, US
Rotimi Olojo - Portland OR, US

International Classification:

G01N 31/22

US Classification:

436164000

Abstract:

Two highly sensitive spectrophotometric methods are developed and described for the measurement of superoxide ion radical derived from KOas well as O generated from either the xanthine-xanthine oxidase reaction or by the addition of NADH to skeletal muscle sarcoplasmic reticulum (SR) vesicles. These methods allow quantification of superoxide ion concentration by monitoring its reaction with 4-Chloro-7-nitrobenzo-2-oxa-1,3-diazole, (NBD-Cl), either by recording absorbance of the final reaction product at a wavelength of 470 nm or by measuring its fluorescence emission intensity at 550 nm using an excitation wavelength of 470 nm. The extinction coefficient of the active product was determined to be 4000 Mcm. A lower limit second-order bimolecular rate constant of 1.50.3×10Mswas estimated from kinetic stopped-flow analysis for the reaction between NBD-Cl and KO. A plot of absorbance versus concentration of superoxide was linear over the range 2-200 μM KOwhile higher sensitivities were obtained from fluorometric measurements down into sub-micromolar concentrations with a limit of detection of 100 nM KO. This new spectrophotometric assay showed higher specificity when compared to some other commonly used methods for detection of superoxide (i.e. nitroblue tetrazolium). Results presented showed good experimental agreements with rates obtained for the measurement of superoxide ion when compared to other well known probes such as acetylated ferri cytochrome-C and XTT. A detailed discussion of the advantages and limitations of this new superoxide ion probe is presented.

US Patent:

20080166814, Jul 10, 2008

Filed:

Feb 9, 2006

Appl. No.:

11/884051

Inventors:

Jonathan J. Abramson - Beaverton OR, US
Benjamin S. Marinov - Portland OR, US

International Classification:

G01N 33/68
G01N 33/00

US Classification:

436 86, 436127

Abstract:

A method for identifying the redox activity of a subject compound is disclosed. The method can be performed aerobically and can include forming a mixture comprising a free-radical precursor and a compound to be tested, and converting the free-radical precursor into a free-radical anion and a free-radical cation. After the free radical cation and the free radical anion have been formed, the relative redox activity of the subject compound may cause a difference in the rate of photo-bleaching of the mixture and/or the rate of superoxide generation. These differences can be quantified and used to identify the redox activity of the subject compound. This sensitive technique for measuring redox activity can be used to screen compounds for various biological applications. Drugs also can be developed based on the relationship between redox activity and biological activity for particular biological applications.

US Patent:

20120101085, Apr 26, 2012

Filed:

Apr 15, 2010

Appl. No.:

13/264055

Inventors:

Jonathan J. Abramson - Portland OR, US

Assignee:

State of Oregon By and Through the State Board of Higher Education on Behalf of Portland State Univ. - Portland OR

International Classification:

A61K 31/554
C07D 417/06
A61P 21/00
A61K 31/136
A61P 9/00
C07D 417/14
A61K 31/085

US Classification:

51421109, 540552, 514718, 514646

Abstract:

The present teachings provide compounds of Formulae I and II: and pharmaceutically acceptable salts, hydrates, complexes, esters, and prodrugs thereof, wherein R, R, R, R, R, R, and X are as defined herein. The present teachings also provide methods of making the compounds of formulae I and II, and methods of treating RyR-associated conditions, disorders, and diseases that include administering a therapeutically effective amount of a compound of formula I or II to a subject in need thereof. In addition, the present teachings relate to methods of reducing the open probability of a ryanodine receptor, and methods of reducing Ca release across a ryanodine receptor (e.g., into the cytoplasm of a cell), by contacting a compound of formula I or II with a ryanodine receptor.