Inhibitors of oxidized low-density lipoprotein receptor 1 and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11465972-B2
Application number	US-201916721103-A
Country	US
Kind code	B2
Filing date	Dec 19, 2019
Priority date	Oct 30, 2015
Publication date	Oct 11, 2022
Grant date	Oct 11, 2022

Abstract

Inhibitors of oxidized low-density lipoprotein receptor 1 (LOX-1), compositions comprising inhibitors of LOX-1, and methods of using thereof are described.

First claim

What is claimed is:

1. A method of inhibiting oxidized low-density lipoprotein receptor 1 (LOX-1) in a cell, the method comprising contacting the cell with an effective amount of a compound having a structure represented by a formula:

wherein:
X is selected from the group consisting of oxygen, sulfur, sulfoxide, sulfone, and NH;
R 1 is selected from the group consisting of hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, aryl, halogen, aminoalkyl, amino, phosphoro, sulfhydryl, sulfino, sulfo, and cyano;
R 2 is selected from the group consisting of hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, unsubstituted aryl, halogen, aminoalkyl, amino, phosphoro, sulfhydryl, sulfino, sulfo, and cyano;
R 3 is selected from the group consisting of hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, aryl, halogen, aminoalkyl, amino, phosphoro, sulfhydryl, sulfino, sulfo, and cyano;
R 5 is hydroxyl; and
each of R 6 , R 7 , R 8 , R 9 , and R 10 is independently selected from the group consisting of hydrogen, hydroxyl, aldehyde, haloformyl, hydroperoxyl, alkyl, alkenyl, alkynyl, aryl, halogen, phosphoro, sulfhydryl, sulfino, sulfo, and cyano, thereby inhibiting oxidized LOX-1.

2. The method of claim 1 , wherein X is oxygen.

3. The method of claim 1 , wherein R 1 is selected from the group consisting of hydrogen, amino, and C1-C5 alkyl.

4. The method of claim 1 , wherein R 2 is selected from the group consisting of hydrogen and C1-C5 alkyl.

5. The method of claim 1 , wherein R 3 is selected from the group consisting of hydrogen, C1-C5 alkyl, cyano, and halogen.

6. A method of inhibiting oxidized low-density lipoprotein receptor 1 (LOX-1) in a cell, the method comprising contacting the cell with an effective amount of a compound selected from:

thereby inhibiting oxidized LOX-1.

7. The method of claim 1 , wherein the compound is:

8. The method of claim 1 , wherein the cell is human.

9. The method of claim 1 , wherein the cell has been isolated from a subject prior to the administering step.

10. The method of claim 1 , wherein contacting is via administration to a subject.

11. The method of claim 10 , wherein the subject has been diagnosed with a need for treatment of a disorder associated with LOX-1 activity or elevated levels of ox-LDL.

Assignees

• Us Gov Veterans Affairs
• Bioventures Llc
• Us Gov Veterans Affairs

Inventors

• Mehta Jawahar L
• Khaidakov Magomed
• Varughese Kottayil I
• Thakkar Shraddha
• Dai Yao
• Crooks Peter
• Penthala Narsimha Reddy

Classifications

• C07D231/38

  Nitrogen atoms (nitro radicals C07D231/16) · CPC title

• C07D231/14

  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 ring carbon atoms · CPC title

• C07D233/22

  Radicals substituted by oxygen atoms · CPC title

• C07D231/12 Primary

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• A61K31/415

  1,2-Diazoles · CPC title