# US 10,246,419 B2 · Liver X receptor (LXR) modulators

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,246,419 B2
- Document ID: US10246419B2
- Status: Granted
- Kind: B2
- Application number: 16/054,884
- Filed: 2018-08-03
- Published: 2018-12-06
- Granted: 2019-04-02
- Earliest claimed: 2013-09-04
- Assignees: Ralexar Therapeutics, Inc.
- Applicants: Ralexar Therapeutics, Inc.
- Inventors: Raju Mohan
- Web page: https://patentgrep.com/patent/US10246419B2

## CPC

- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A61K 31/415: 1,2-Diazoles
- A61K 31/4164: 1,3-Diazoles
- A61K 31/422: not condensed and containing further heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/16: Anti-Parkinson drugs
- 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
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 231/14: 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
- C07D 233/10: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring nitrogen atoms
- C07D 233/64: with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- C07D 409/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Described herein are liver X receptor (LXR) modulators and methods of utilizing LXR modulators in the treatment of LXR-associated diseases, disorders or conditions. Also described herein are pharmaceutical compositions containing such compounds.

## Claims

### Claim 1

A method of treating a disease, disorder, or condition in a mammal that would benefit from LXR modulation comprising administering to the mammal a compound of Formula (IA):
or a pharmaceutically acceptable salt thereof, wherein:
L1 is a bond;
R1 is —OR9, —N(R9)2, C1-C6alkyl, C2-C6alkenyl, C1-C6haloalkyl, C2-C9heterocycloalkyl, —C(═O)R8, or —C(═O)N(R9)2;
R2 is C1-C6alkyl, C2-C6alkenyl, C3-C8cycloalkyl, or —C1-C6alkyl-C3-C8cycloalkyl;
R3 is hydrogen or halogen;
R4 is aryl; wherein aryl is substituted with at least one R11;
each R5 is independently halogen, C1-C6alkyl, or C1-C6haloalkyl;
R8 is C1-C6alkyl, C2-C6alkenyl, C1-C6haloalkyl, —C1-C6alkyl-aryl, aryl, or heteroaryl;
each R9 is independently hydrogen, C1-C6alkyl, or C1-C6haloalkyl;
each R10 is independently hydrogen or C1-C6alkyl;
each R11 is independently halogen, nitro, —OR10, —N(R10)2, —CN, —C(═O)R10, —C(═O)OR10, —C(═O)N(R10)2, —NR10C(═O)R10, —NR10SO2R10, —SOR10, —SO2R10, —SO2N(R10)2, —C(═O)OCH2SCH3, optionally substituted C1-C6alkyl, or optionally substituted C1-C6haloalkyl;
wherein at least one R11 is —NR10SO2R10, —SOR10, —SO2R10, or —SO2N(R10)2; and
n is 0.

### Claim 2 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is C1-C6alkyl.

### Claim 3 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is C2-C6alkenyl.

### Claim 4 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is C1-C6haloalkyl.

### Claim 5 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein -L1-R1 is —C(═CH2)CH3, isopropyl, —C(═O)NHCH2CF3, —CF3, or —C(CH3)2OH.

### Claim 6 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is C1-C6alkyl.

### Claim 7 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is isobutyl, sec-butyl, cyclohexyl, —CH2-cyclohexyl, or —CH2-cyclopropyl.

### Claim 8 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R10 is independently C1-C6alkyl.

### Claim 9 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein R4 is phenyl substituted with one R11, wherein R11 is —SO2R10 and R10 is C1-C6alkyl; or R4 is phenyl substituted with two R11, and one R11 is —SO2R10, and one R11 is optionally substituted C1-C6alkyl.

### Claim 10 (depends on 1)

The method of claim 1, wherein the compound is a compound of Formula (TB):
wherein:
R11a is —NR10SO2R10, —SO2R10, or —SO2(R10)2; and
m is 0 or 1;
or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 1)

The method of claim 1, wherein the compound is a compound of Formula (IC):
wherein m is 0 or 1;
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
R1 is —OR9, —C1-C6alkyl, C2-C6alkenyl, C1-C6haloalkyl, or —C(═O)N(R9)2;
R2 is C1-C6alkyl, C3-C8cycloalkyl, or —C1-C6alkyl-C3-C8cycloalkyl;
R3 is hydrogen;
R4 is phenyl substituted with at least one R11;
each R11 is independently —NR10SO2R10, —SOR10, —SO2R10, —SO2N(R10)2, or C1-C6alkyl, wherein said C1-C6alkyl is optionally substituted by 1 hydroxy;
provided that at least one R11 is —NR10SO2R10, —SOR10, —SO2R10, —SO2N(R10)2, or C1-C6alkyl,
each R10 is independently C1-C6alkyl; and
each R9 is independently hydrogen or C1-C6haloalkyl.

### Claim 13 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
R1 is —OR9, —C1-C6alkyl, C2-C6alkenyl, C1-C6haloalkyl, or —C(═O)N(R9)2;
R2 is C1-C6alkyl, C3-C8Cycloalkyl, or —C1-C6alkyl-C3-C8cycloalkyl;
R3 is hydrogen;
R4 is phenyl substituted with at R11, wherein R11 is —SO2R10 and R10 is C1-C6alkyl; or
R4 is phenyl substituted with two R11, wherein one R11 is —SO2R10 and one R11 is optionally substituted C1-C6alkyl; and
each R9 is independently hydrogen or C1-C6haloalkyl.

### Claim 14 (depends on 1)

The method of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
-L1-R1 is —C(═CH2)CH3, isopropyl, —C(═O)NHCH2CF3, —CF3, or —C(CH3)2OH;
R2 is isobutyl, sec-butyl, cyclohexyl, —CH2-cyclohexyl, or —CH2-cyclopropyl;
R3 is hydrogen; and
R4 is phenyl substituted with two R11, wherein one is —SO2CH3 and one R11 is —CH2OH; or R4 is phenyl substituted with one R11, wherein R11 is —SO2R10 and R10 is CH3.

### Claim 15 (depends on 1)

The method of claim 1, wherein the compound of Formula (IA) is selected from:
or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 1)

The method of claim 1, wherein the disease, disorder, or condition in a mammal is increased lipid levels, increased cholesterol levels, low HDL-cholesterol, high LDL-cholesterol, atherosclerotic diseases, diabetes, non-insulin dependent diabetes mellitus, metabolic syndrome, dyslipidemia, sepsis, inflammatory diseases, skin diseases, colitis, pancreatitis, cholestasis of the liver, fibrosis of the liver, psoriasis, Alzheimer's disease, Parkinson's disease, impaired/improvable cognitive function, HIV, metastatic melanoma, acute macular degeneration, and age related forms of macular degeneration.

### Claim 17 (depends on 16)

The method of claim 16, further comprising administering a second therapeutic agent.

### Claim 18 (depends on 1)

The method of claim 1, wherein the mammal is a human.