# US 10,501,423 B2 · Substituted phenyl sulfonyl phenyl triazole thiones and uses thereof

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- Number: US 10,501,423 B2
- Document ID: US10501423B2
- Status: Granted
- Kind: B2
- Application number: 16/366,793
- Filed: 2019-03-27
- Published: 2019-09-26
- Granted: 2019-12-10
- Earliest claimed: 2017-10-30
- Assignees: Neuropore Therapies, Inc.
- Applicants: Neuropore Therapies, Inc.
- Inventors: Wolfgang J. Wrasidlo; Emily M. Stocking; Srinivasa Reddy Natala; Diana Luz Price
- Web page: https://patentgrep.com/patent/US10501423B2

## CPC

- A61P 25/00: Drugs for disorders of the nervous system
- C07D 249/12: Oxygen or sulfur atoms
- A61K 9/10: Dispersions; Emulsions
- A61K 31/18: Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63)
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- 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 243/10: condensed with carbocyclic rings or ring systems
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The present disclosure relates to substituted phenyl sulfonyl phenyl triazole thiones, pharmaceutical compositions containing them, and methods of using them.

## Claims

### Claim 1

A compound of Formula (I):
wherein
R1, R2, and R3 are each independently hydrogen, hydroxy, halogen, optionally substituted C1-4 alkyl, optionally substituted C1-4 alkoxy, —CN, —C(O)Rx, —C(O)ORx, —S(O)2Rx, or —NRyRz;
Rx, Ry, and Rz are each independently H or optionally substituted C1-4 alkyl, or Ry and Rz taken together with the nitrogen to which they are attached form an optionally substituted monocyclic heterocycloalkyl ring;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is hydrogen.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is —OCH2CH2—O—CH2CH3 or —OCH2CH2OCH3.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is —NHCH2CH2OH or —N(CH2CH3)2.

### Claim 5 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is morpholinyl, 4-methyl-piperazin-1-yl, piperidinyl, or pyrrolidinyl.

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen, C1-4 alkyl, or substituted C1-4 alkyl.

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is CF3.

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is methyl.

### Claim 9 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is optionally substituted C1-4 alkoxy, —CN, or —NRyRz.

### Claim 10 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is —N(CH3)2.

### Claim 11 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is morpholinyl.

### Claim 12 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is methoxy, —OCH2CH2—O—CH2CH3, or —OCH2CH2OCH3.

### Claim 13 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3 is halogen.

### Claim 14 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3 is chloro.

### Claim 15 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3 is hydrogen.

### Claim 16 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3 is methyl.

### Claim 17 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3 is —CN.

### Claim 18 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3 is morpholinyl.

### Claim 19 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R3 is C1-4 alkoxy.

### Claim 20 (depends on 1)

The compound of claim 1, wherein the compound is selected from the group consisting of
Compound
No.
Structure
Name
1
4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)phenyl)- 2,4-dihydro-2H-1,2,4-triazole-3-thione;
2
4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2- morpholinophenyl)-2,4-dihydro-3H- 1,2,4-triazole-3-thione;
3
4-(4-(phenylsulfonyl)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione;
4
4-(4-((4-chlorophenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione;
5
4-(4-((4-chloro-3- methylphenyl)sulfonyl)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione;
6
4-((4-(5-thioxo-1,5-dihydro-4H-1,2,4- triazol-4- yl)phenyl)sulfonyl)benzonitrile;
7
4-(4-((4- morpholinophenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione;
8
4-(4-((4- methoxyphenyl)sulfonyl)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione;
9
4-(4-tosylphenyl)-2,4-dihydro-3H-1,2,4- triazole-3-thione;
10
4-(4-((4-fluorophenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione;
11
4-(4-((3- (trifluoromethyl)phenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione;
12
4-(4-((3- methoxyphenyl)sulfonyl)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione;
13
4-(4-((3-(2- ethoxyethoxy)phenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione;
14
3-((4-(5-thioxo-1,5-dihydro-4H-1,2,4- triazol-4- yl)phenyl)sulfonyl)benzonitrile;
15
4-(4-((3- (dimethylamino)phenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione;
16
4-(4-((3- morpholinophenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione;
17
4-(4-(m-tolylsulfonyl)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione;
18
4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2-((2- hydroxyethyl)amino)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione;
19
4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2- (piperidin-1-yl)phenyl)-2,4-dihydro-3H- 1,2,4-triazole-3-thione;
20
4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2-(4- methylpiperazin-1-yl)phenyl)-2,4- dihydro-3H-1,2,4-triazole-3-thione;
21
4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2- (diethylamino)phenyl)-2,4-dihydro-3H- 1,2,4-triaozle-3-thione;
22
4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2-(2- ethoxyethoxy)phenyl)-2,4-dihydro-3H- 1,2,4-triazole-3-thione;
23
4-(4-((4-methyl-3- (trifluoromethyl)phenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione;
24
4-(4-((4-chloro-3- (trifluoromethyl)phenyl)sulfonyl)-2- (pyrrolidin-1-yl)phenyl)-2,4-dihydro- 3H-1,2,4-triazole-3-thione; and
25
4-(4-((3-(2- methoxyethoxy)phenyl)sulfonyl)phenyl)- 2,4-dihydro-3H-1,2,4-triazole-3-thione,
or a pharmaceutically acceptable salt thereof.

### Claim 21 (depends on 1)

The compound of claim 1, wherein the compound is:
or a pharmaceutically acceptable salt thereof.

### Claim 22 (depends on 1)

The compound of claim 1, wherein the compound is:
or a pharmaceutically acceptable salt thereof.

### Claim 23 (depends on 1)

A pharmaceutical composition comprising (a) at least one compound of claim 1, or a pharmaceutically acceptable salt thereof, and (b) a pharmaceutically acceptable excipient.