# US 10,766,878 B2 · Sulfonylcycloalkyl carboxamide compounds

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- Number: US 10,766,878 B2
- Document ID: US10766878B2
- Status: Granted
- Kind: B2
- Application number: 16/247,995
- Filed: 2019-01-15
- Published: 2019-05-16
- Granted: 2020-09-08
- Earliest claimed: 2017-07-18
- Assignees: Genentech, Inc.
- Applicants: Genentech, Inc.
- Inventors: Baihua Hu; Vishal Verma; Matthew Volgraf; Anthony Estrada; Joseph Lyssikatos
- Web page: https://patentgrep.com/patent/US10766878B2

## CPC

- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 11/14: Antitussive agents
- A61P 13/00: Drugs for disorders of the urinary system
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 17/04: Antipruritics
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 27/16: Otologicals
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 213/61: Halogen atoms or nitro radicals
- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 231/16: Halogen atoms or nitro radicals
- C07D 231/20: One oxygen atom attached in position 3 or 5
- C07D 237/08: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 239/26: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention is concerned with the compounds of formula I: and pharmaceutically acceptable salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

## Claims

### Claim 1

A compound of formula (I) or a pharmaceutically acceptable salt thereof:
wherein:
n is 2 or 3;
R1 is aryl or heteoraryl, each optionally substituted with one or more groups independently selected from halogen, —CN, —C1-6 alkyl and —C1-6 haloalkyl;
m is 0, 1, 2, or 3;
each R2 is independently selected from halogen, —C1-6 alkyl, —C1-6 haloalkyl, —O—C1-6 alkyl, —C3-7 cycloalkyl, and —CN;
R3 is an amide selected from the orientation —NH—C(O)— and —C(O)—NH—;
R4 is a 4, 5, 6 or 7-membered heterocycle, aryl or heteroaryl optionally substituted with one or more groups independently selected from halogen, —C1-6 alkyl, —C1-6 haloalkyl, —O—C1-6 haloalkyl, and —CN;
A is selected from A1, A2 and A3 wherein:
A1 is unsubstituted or substituted 5-membered heteroaryl comprising one or two nitrogen hetero atoms;
A2 is unsubstituted or substituted aryl; and
A3 is unsubstituted or substituted 6-membered heteroaryl comprising one or two hetero nitrogen atoms; and
each * independently denotes a chiral center (i) in an R configuration or in an S configuration or (ii) a mixture of R and S configurations for a plurality of compounds of formula (I).

### Claim 2 (depends on 1)

The compound of claim 1 wherein n is 2.

### Claim 3 (depends on 1)

The compound of claim 1 wherein n is 3.

### Claim 4 (depends on 1)

The compound of claim 1 wherein R1 is aryl substituted with a substituent selected from Br, Cl, F, —CHF2, —CF3, CHCl2 and —CCl3 at any of the ortho, meta or para positions.

### Claim 5 (depends on 4)

The compound of claim 4 wherein R1 is:

### Claim 6 (depends on 1)

The compound of claim 1 wherein m is 0.

### Claim 7 (depends on 1)

The compound of claim 1 wherein m is 1 or 2 and wherein each R2 is independently selected from —CH3, —CH2CH3, —CH2-cyclopropane, —CF3, —CN and F.

### Claim 8 (depends on 1)

The compound of claim 1 wherein R3 is —NH—C(O)—.

### Claim 9 (depends on 1)

The compound of claim 1 wherein R3 is —C(O)—NH—.

### Claim 10 (depends on 1)

The compound of claim 1 wherein A is A1, wherein A1 is selected from:
wherein p is 0 or 1 and wherein R5 is selected from halogen, —O—C1-6 alkyl, —C1-6 haloalkyl and —C3-7 cycloalkyl.

### Claim 11 (depends on 10)

The compound of claim 10 wherein A1 is selected from:

### Claim 12 (depends on 1)

The compound of claim 1 wherein A is A2, wherein A2 is of the structure:
wherein q is 0, 1 or 2, and wherein each R6, when present, is independently selected from halogen, O—C1-6 alkyl and C1-6 haloalkyl.

### Claim 13 (depends on 12)

The compound of claim 12 wherein A2 is:

### Claim 14 (depends on 1)

The compound of claim 1 wherein A is A3, wherein A3 is of the structure:
wherein:
(1) X1, X2 and X3 are independently selected from C and N wherein
(i) one of X1, X2 and X3 is N and r is 0, 1 or 2, or
(ii) X1 and X3 are each N and r is 0 or 1; and
(2) each R7 is independently selected from halogen, O—C1-6 alkyl, and C1-6 haloalkyl.

### Claim 15 (depends on 14)

The compound of claim 14 wherein A3 is selected from:

### Claim 16 (depends on 1)

The compound of claim 1 wherein R4 is:
wherein:
Y1 and Y2 are independently selected from C and N;
s is 0 or 1; and
each R8 is independently selected from halogen, —O—C1-6 haloalkyl, and —C1-6 haloalkyl.

### Claim 17 (depends on 16)

The compound of claim 16 wherein R4 is selected from:

### Claim 18 (depends on 1)

A compound of claim 1 selected from:

### Claim 19 (depends on 1)

A compound of claim 1 selected from:

### Claim 20

A compound selected from:

### Claim 21

A compound selected from:

### Claim 22

A compound selected from:

### Claim 23 (depends on 1)

A pharmaceutical composition, comprising a compound as described in any one of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.