# US 8,772,343 B2 · Chemical compounds

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- Number: US 8,772,343 B2
- Document ID: US8772343B2
- Status: Granted
- Kind: B2
- Application number: 13/808,658
- Filed: 2011-07-06
- Published: 2013-05-09
- Granted: 2014-07-08
- Earliest claimed: 2010-07-12
- Assignees: Pfizer Inc.
- Applicants: Andrew Simon Bell; Alan Daniel Brown; Russell Andrew Lewthwaite; Manuel Perez-Pacheco; David James Rawson; Robert Ian Storer; Nigel Alan Swain
- Inventors: Andrew Simon Bell; Alan Daniel Brown; Russell Andrew Lewthwaite; Manuel Perez-Pacheco; David James Rawson; Robert Ian Storer; Nigel Alan Swain
- Web page: https://patentgrep.com/patent/US8772343B2

## CPC

- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/18: Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63)
- A61K 31/4164: 1,3-Diazoles
- A61K 31/4418: having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07C 311/13: the carbon skeleton containing six-membered aromatic rings
- C07C 311/51: Y being a hydrogen or a carbon atom
- C07D 213/64: attached in position 2 or 6
- C07D 213/65: attached in position 3 or 5
- C07D 213/69: Two or more oxygen atoms
- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 233/64: with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- C07D 239/26: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 239/42: One nitrogen atom (nitro radicals C07D239/30)
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- 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
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention relates to sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to a new sulfonamide Nav1.7 inhibitors of formula 10 (I):(I) or a pharmaceutically acceptable salt thereof, wherein Z, R1, R2, R3, R4 and R5 are as defined in the description. Nav1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain.

## Claims

### Claim 1

A compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
Z is a group selected from naphthyl, phenyl and Het1, said group being optionally independently substituted by one to three substituents selected from Y1 and Y2;
Y1 and Y2 are independently selected from F; CI; CN; (C1-C8)alkyl, optionally substituted by (C3-C8)cycloalkyl or one to three F; (C3-C8)cycloalkyl, optionally substituted by one to three F; NR7R8; (C1-C8)alkyloxy, optionally independently substituted by one to three R9; (C3-C8)cycloalkyloxy; phenyl, optionally independently substituted by one to three R10; Het2; and Het3; wherein (C3-C8)cycloalkyloxy may be optionally fused to a phenyl ring or may be independently substituted by one to three R10;
R1 is (C1-C6)alkyl or (C3-C8)cycloalkyl, each of which is optionally substituted by one to three F;
R2, R3, R4 are independently H, F, Cl or —OCH3;
R5 is phenyl optionally substituted by one to three substituents independently selected from CN, CI, F and R6; or Het3;
R6 is a group selected from (C1-C6)alkyl and (C1-C6)alkyloxy, wherein each group is optionally substituted, valency permitting, by one to five F;
R7 and R8 are independently H; (C1-C8)alkyl, optionally independently substituted by one to three R11; (C3-C8)cycloalkyl; or ‘C-linked’ Het2; wherein (C3-C8)cycloalkyl may be optionally fused to a phenyl ring or may be independently substituted by one to three R10; or
R7 and R8, taken together with the nitrogen atom to which they are attached, form a saturated, bridged, 7- to 9-membered ring;
R9 is F; (C1-C6)alkyloxy; (C3-C8)cycloalkyl, optionally substituted by one to three F; Het1; or phenyl, optionally independently substituted by one to three R6;
R10 is F, Cl or R6;
R11 is F; (C1-C6)alkyloxy; (C3-C8)cycloalkyl, optionally substituted by one to three F; ‘C-linked’ Het1; or phenyl, optionally independently substituted by one to three R6;
Het1 is a 6-, 9- or 10-membered heteroaryl comprising one to three nitrogen atoms;
Het2 is a 3- to 8-membered saturated monoheterocycloalkyl comprising one or two ring members selected from —NR12— and —O—, said monoheterocycloalkyl being optionally substituted on a ring carbon atom by one to three substituents independently selected from F, (C1-C6)alkyl, (C1-C4)alkyloxy(C0-C4)alkylene and (C3-C8)cycloalkyl;
Het3 is a 5- or 6-membered heteroaryl comprising one to three nitrogen atoms, said heteroaryl being optionally substituted by one to three substituents selected from F, Cl, CN and R6; and
R12 is H, (C1-C6)alkyl or (C3-C8)cycloalkyl, wherein (C1-C6)alkyl and (C3-C8)cycloalkyl are optionally substituted by one to three F; or, when Het2 is ‘N-linked’, is absent.

### Claim 2 (depends on 1)

A compound according to claim 1 wherein Z is phenyl optionally independently substituted by one to three substituents selected from Y1 and Y2.

### Claim 3 (depends on 1)

A compound according to claim 1 wherein wherein Z is phenyl optionally independently substituted by one or two substituents selected from Y1 and Y2.

### Claim 4 (depends on 1)

A compound according to claim 1 wherein Z is phenyl para-substituted by Y2.

### Claim 5 (depends on 1)

A compound according to claim 1 wherein Z is a 6-membered heteroaryl comprising one to three nitrogen atoms, said heteroaryl being optionally independently substituted by one to three substituents selected from Y1 and Y2.

### Claim 6 (depends on 1)

A compound according to claims 1 wherein Z is pyridyl optionally independently substituted by one to three substituents selected from Y1 and Y2.

### Claim 7 (depends on 1)

A compound according to claim 1 wherein Z is pyridyl optionally independently substituted by one or two substituents selected from Y1 and Y2.

### Claim 8 (depends on 1)

A compound according to claim 1 wherein Z is pyridyl optionally independently substituted by one or two substituents selected from Y1 and Y2 and wherein said pyridyl is orientated as below:

### Claim 9 (depends on 8)

A compound according to claim 8 wherein said pyridyl is 2-substituted or, where di-substituted, 2- and 3-substituted.

### Claim 10 (depends on 1)

A compound according to claim 1 wherein R1 is (C1-C4)alkyl or (C3-C6)cycloalkyl.

### Claim 11 (depends on 1)

A compound according to claim 1 wherein R2, R3 and R4 are independently H or F.

### Claim 12 (depends on 1)

A compound according to claim 1 wherein R5 is (i) phenyl optionally substituted by one or two substituents independently selected from CN, Cl, F and R6; or (ii) a 5- or 6-membered heteroaryl comprising one or two nitrogen atoms, said heteroaryl being optionally substituted by one or two substituents selected from F, CI, CN and R6.

### Claim 13 (depends on 1)

A compound according to claim 1 wherein R5 is (i) phenyl optionally substituted by CN, Cl, F or R6; or (ii) a heteroaryl selected from pyrazolyl, pyridyl or pyrimidinyl, said heteroaryl being optionally substituted by (C1-C6)alkyloxy or (C1-C6)alkyloxy substituted, valency permitting, by one to five F.

### Claim 14 (depends on 1)

A compound according to claim 1 wherein R6 is a group selected from CH3, C2H5, CF3, —OCH3, —OC2H5 or —OCF3.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof together, as defined in claim 1, with one or more pharmaceutically acceptable excipients.

### Claim 16 (depends on 15)

A pharmaceutical composition according to claim 15 including one or more additional therapeutic agents.