# US 10,308,635 B2 · 1-sulfonyl piperidine derivatives as modulators of prokineticin receptors

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- Number: US 10,308,635 B2
- Document ID: US10308635B2
- Status: Granted
- Kind: B2
- Application number: 15/971,330
- Filed: 2018-05-04
- Published: 2018-09-06
- Granted: 2019-06-04
- Earliest claimed: 2013-06-21
- Assignees: Takeda Pharmaceutical Company Limited
- Applicants: Takeda Pharmaceutical Company Limited
- Inventors: Martin Teall
- Web page: https://patentgrep.com/patent/US10308635B2

## CPC

- C07D 401/12: linked by a chain containing hetero atoms as chain links
- A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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: 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

The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof in which m, n, W, X, Y, Z, R1, R2, R3, R4 and R5 are as defined in the specification, compositions containing them and their use in therapy.

## Claims

### Claim 1

A method for the treatment of pain comprising the step:
administering to a patient in need thereof, a therapeutically effective amount of a compound selected from the group consisting of:
Methyl 2-(4-Chlorophenyl)-2-(1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene)acetate,
2-(4-Chlorophenyl)-2-(1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene)acetonitrile,
2-(2,6-Difluorophenyl)-2-(1((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene)acetonitrile,
2-(4-Chloro-2-fluorophenyl)-2-(1((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene)acetonitrile,
2-(4-Chlorophenyl)-2-(1-((3,5-diethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene)acetonitrile,
2-(4-Chlorophenyl)-2-(1-((1,5-dimethyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene)acetonitrile,
2-(2,6-Difluorophenyl)-2-(1-((1,3,5-trimethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene)acetonitrile,
2-(1((3,5-Dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene)-2-(4-(trifluoromethoxy)phenyl)acetonitrile,
2-(4-Chlorophenyl)-2-(1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)-3-methylpiperidin-4-ylidene)acetonitrile,
4-(4-Chloro-2-fluorobenzylidene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine,
4-(4-Chloro-2-fluorobenzylidene)-1-((1,3,5-trimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine,
4-(1-(4-Chlorophenyl)ethylidene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine,
4-(4-Chlorobenzylidene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine,
2-(4-Chlorophenyl)-2-(1-((1,3,5-trimethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene)acetonitrile,
4-((4-Chlorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine,
4-((3-Chloro-4-fluorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine,
4-((2,4-Dichlorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine,
4-((3,4-Dichlorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine,
4-((4-Chloro-3-fluorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine,
4-((4-Chloro-2-fluorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine,
4-((2,4-Difluorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine,
3-((1-((3,5-Dimethyl- 1H-pyrazol-4-yl)sulfonyl)piperidin-4-ylidene)fluoromethyl)quinolone and pharmaceutically acceptable salts of any one thereof.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the compound is 4-((4-chloro-3-fluorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the compound is 4-((4-chloro-2-fluorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the compound is 4-((4-chloro-3-fluorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the compound is 4-((4-chloro-2-fluorophenyl)fluoromethylene)-1-((3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl)piperidine.