# US 10,246,453 B2 · Benzenesulfonamide compounds and their use as therapeutic agents

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

- Number: US 10,246,453 B2
- Document ID: US10246453B2
- Status: Granted
- Kind: B2
- Application number: 15/600,490
- Filed: 2017-05-19
- Published: 2017-11-23
- Granted: 2019-04-02
- Earliest claimed: 2016-05-20
- Assignees: Xenon Pharmaceuticals Inc.
- Applicants: Xenon Pharmaceuticals Inc.
- Inventors: Jean-Christophe Andrez; Kristen Nicole Burford; Sultan Chowdhury; Charles Jay Cohen; Christoph Martin Dehnhardt; Robert Joseph Devita; James Roy Empfield; Thilo Focken; Michael Edward Grimwood; Syed Abid Hasan; James Philip Johnson, Jr.; Alla Yurevna Zenova
- Web page: https://patentgrep.com/patent/US10246453B2

## CPC

- C07D 451/06: Oxygen atoms
- A61P 3/12: for electrolyte homeostasis
- A61P 25/08: Antiepileptics; Anticonvulsants
- C07D 213/76: to which a second hetero atom is attached (nitro radicals C07D213/61)
- C07D 237/20: Nitrogen atoms (nitro radicals C07D237/12)
- C07D 239/69: Benzenesulfonamido-pyrimidines
- C07D 261/16: Benzene-sulfonamido isoxazoles
- C07D 277/52: to sulfur atoms, e.g. sulfonamides
- C07D 285/08: 1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07D 493/10: Spiro-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention is directed to benzenesulfonamide compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment of diseases or conditions associated with voltage-gated sodium channels, such as epilepsy.

## Claims

### Claim 1

A compound of formula (I):
wherein:
n is 1, 2, or 3;
m is 1, 2, 3 or 4;
X is a direct bond or —C(R9)R10—;
Y is a direct bond or —C(R11)R12—;
R1 is hydrogen, alkyl, —R17—OR14, an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted N-heterocyclyl, an optionally substituted N-heteroaryl, an optionally substituted O-heteroaryl or an optionally substituted S-heteroaryl;
R2 is an optionally substituted 5-membered N-heteroaryl or an optionally substituted 6-membered N-heteroaryl;
R3 is —O — or —N(R13)—;
R4 and R5 are each independently hydrogen, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl;
or R4 and R1, together with the carbon to which they are attached, form an optionally substituted cycloalkyl, an optionally substituted heterocyclyl or an optionally substituted aryl, and R5, if present, is hydrogen, alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl;
each R6 is independently hydrogen, alkyl, alkenyl, halo, haloalkyl, cyano, —OR14 or optionally substituted cycloalkyl;
R7 is halo, haloalkyl, cyano or —OR14;
each R8 is independently hydrogen, alkyl, halo, haloalkyl or —OR14;
or two R8's, together with the carbon to which they are both attached, may form an optionally substituted cycloalkyl;
R9,R10, and R12 are each independently hydrogen, alkyl, haloalkyl or —OR14;
or R9 and R11 form an optionally substituted alkylene chain and R10 and R12 are as defined above; and
R13 is hydrogen, alkyl or haloalkyl;
each R14 are each independently hydrogen, alky, haloalkyl, optionally substituted aryl or optionally substituted aralkyl; and
R17 is a direct bond or an optionally substituted alkylene chain;
as an individual stereoisomer, enantiomer or tautomer thereof or a mixture thereof;
or a pharmaceutically acceptable salt, solvate or prodrug thereof;
provided that when R3 is —O—, R2 is not optionally substituted thiadiazolyl.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R3 is —O—, wherein the compound has the following formula (Ia):
wherein m, n, X, Y, R1, R2, R4, R5, R6, R7 and R8 are each as defined above in claim 1;
as an individual stereoisomer, enantiomer or tautomer thereof or a mixture thereof;
or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 3 (depends on 2)

The compound of claim 2, wherein:
n is 1 or 2;
m is 1 or 2;
X is a direct bond or —C(R9)R10—;
Y is a direct bond or —C(R11)R12—;
R1 is hydrogen, alkyl, —R17—OR14, an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted N-heterocyclyl, an optionally substituted N-heteroaryl, an optionally substituted O-heteroaryl or an optionally substituted S-heteroaryl;
R2 is an optionally substituted 5-membered N-heteroaryl or an optionally substituted 6-membered N-heteroaryl;
R4 and R5 are each independently hydrogen, alkyl or haloalkyl;
or R4 and R1, together with the carbon to which they are attached, form an optionally substituted cycloalkyl or an optionally substituted aryl, and R5, if present, if present, is hydrogen, alkyl, haloalkyl or optionally substituted aryl;
each R6 is independently hydrogen, alkyl, alkenyl, halo, haloalkyl, cyano, —OR14 or optionally substituted cycloalkyl;
R7 is halo, haloalkyl, cyano or —OR14;
each R8 is independently hydrogen, alkyl, halo, haloalkyl or —OR14;
or two R8's, together with the carbon to which they are both attached, may form an optionally substituted cycloalkyl;
R9, R10, R11 and R12 are each independently hydrogen, alkyl, haloalkyl, alkyl or —OR14;
or R9 and R11 form an optionally substituted alkylene chain and R10and R12 are as defined above; and
each R14 are each independently hydrogen, alky, haloalkyl, optionally substituted aryl or optionally substituted aralkyl; and
R17 is a direct bond or an optionally substituted alkylene chain.

### Claim 4 (depends on 3)

The compound of claim 3, wherein X and Y are both a direct bond,
wherein the compound has the following formula (Ia1):
wherein m, n, R1, R2, R4, R5, R6, R7 and R8 are each as defined above in claim 3;
as an individual stereoisomer, enantiomer or tautomer thereof or a mixture thereof;
or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 5 (depends on 4)

The compound of claim 4, wherein R2 is an optionally substituted 5-membered N-heteroaryl.

### Claim 6 (depends on 5)

The compound of claim 5, wherein R2 is optionally substituted isoxazolyl, optionally substituted thiazolyl or optionally substituted thiadiazolyl.

### Claim 7 (depends on 6)

The compound of claim 6, which is 4((1-benzylazetidin-3-yl)oxy)-3-chloro-N-(thiazol-2-yl)benzene-sulfonamide.

### Claim 8 (depends on 4)

The compound of claim 4, wherein R2 is an optionally substituted 6-membered N-heteroaryl.

### Claim 9 (depends on 8)

The compound of claim 8, wherein R2 is optionally substituted pyridinyl.

### Claim 10 (depends on 3)

The compound of claim 3, wherein X is —C(R9)R10—and Y is a direct bond, wherein the compound has the following formula (Ia 2):
wherein m, n, R1, R2, R4, R5, R6, R7, R8, R9 and R10are each as defined above in claim 3;
as an individual stereoisomer, enantiomer or tautomer thereof or a mixture thereof;
or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 11 (depends on 10)

The compound of claim 10, wherein R2 is an optionally substituted 5-membered N-heteroaryl.

### Claim 12 (depends on 11)

The compound of claim 11, wherein R2 is optionally substituted isoxazolyl, optionally substituted thiazolyl or optionally substituted thiadiazolyl.

### Claim 13 (depends on 12)

The compound of claim 12, selected from:
(S)-4((1-benzyl-3-methylpyrrolidin-3-yl)oxy)-2,6-difluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)oxy)-3-ethyl-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)oxy)-3-bromo-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzyl-3-methylpyrrolidin-3-yl)oxy)-2,6-difluoro-3-methyl-N-(thiazol-2-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)oxy)-2,6-difluoro-N-(thiazol-4-yl)-3-vinylbenzenesulfonamide;
rac-4-((1-benzyl-3-methylpyrrolidin-3-yl)oxy)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzyl-3-methylpyrrolidin-3-yl)oxy)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(R)-4-((1-benzyl-3-methylpyrrolidin-3-yl)oxy)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)oxy)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzyl-3-methylpyrrolidin-3-yl)oxy)-2-fluoro-5-methyl-N-(thiazol-4)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)oxy)-2,6-difluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide; and
(S)-4((1-benzylpyrrolidin-3-yl)oxy)-3-chloro-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide.

### Claim 14 (depends on 10)

The compound of claim 10, wherein R2 is an optionally substituted 6-membered N-heteroaryl.

### Claim 15 (depends on 14)

The compound of claim 14, wherein R2 is optionally substituted pyridinyl.

### Claim 16 (depends on 3)

The compound of claim 3, wherein X is —C(R9)R10—and Y is —C(R11)R12—, wherein the compound has the following formula (Ia3):
wherein m, n, R1, R2R4, R5, R6R7, R8, R9, R9R10R11and R12 are each as defined above in claim 3;
as an individual stereoisomer, enantiomer or tautomer thereof or a mixture thereof;
or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 17 (depends on 16)

The compound of claim 16, wherein R2 is an optionally substituted 5-membered N-heteroaryl.

### Claim 18 (depends on 17)

The compound of claim 17, wherein R2 is optionally substituted isoxazolyl, optionally substituted thiazolyl or optionally substituted thiadiazolyl.

### Claim 19 (depends on 18)

The compound of claim 18, wherein:
R1 is optionally substituted aryl or optionally substituted aralkyl; and
R9 , R10 , R11 and R12 are each independently hydrogen or alkyl.

### Claim 20 (depends on 19)

The compound of claim 19 selected from:
5-chloro-2-fluoro-4-(1-(1-phenylethyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(1-phenylethyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(3-fluorobenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(3-(difluoromethyl)benzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(3-(difluoromethoxy)benzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-((6-methylpyridin-2-yl)methyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(3-methoxybenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(3-chlorobenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(2-fluorobenzyl)-3-methylpiperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(3-methyl-1-(3-methylbenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
4-(1-benzyl-3-methylpiperidin-4-yloxy)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(2-fluorobenzyl)-3-methylpiperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(3-methyl-1-(3-methylbenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
4-(1-benzyl-3-methylpiperidin-4-yloxy)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(naphthalen-2-ylmethyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(2-fluorobenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(2-methylbenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(3-methylbenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(pyridin-2-ylmethyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(pyridin-3-ylmethyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(pyridin-4-ylmethyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(4-methoxybenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(3,4-dimethylbenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(3,5-dimethylbenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(1-(4-methylbenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
4-(1-benzylpiperidin-4-yloxy)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-N-(thiazol-2-yl)-4-(1-(4-(trifluoromethyl)benzyl)piperidin-4-yloxy)benzenesulfonamide;
3-chloro-4-(1-(4-fluorobenzyl)piperidin-4-yloxy)-N-(thiazol-2-yl)benzenesulfonamide;
4-(1-benzylpiperidin-4-yloxy)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4((1-(cyclohexylmethyl)piperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4((1-cyclohexylpiperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-N-(thiazol-2-yl)-4((1-(2-(trifluoromethyl)benzyl)piperidin-4-yl)oxy)benzenesulfonamide;
3-chloro-4((1-(2-chlorobenzyl)piperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4((14(4-methylpyridin-2-ylmethyl)piperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
4-((1-benzyl-4-methylpiperidin-4-yl)oxy)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-((1-(3-chlorobenzyl)-4-methylpiperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-((1-(3-(difluoromethyl)benzyl)-4-methylpiperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-((1-(2,3-dihydro-1H-inden-1yl)piperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
(R)-3-chloro-4((1-(1-phenylethyl)piperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
(R)-5-chloro-2-fluoro-4((1-(1-phenylethyl)piperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
(R)-3-chloro-4((1-(1-phenylethyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-3-chloro-4-((1-(1-phenylethyl)piperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4((1-(2-phenylpropan-2-yl)piperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
5-chloro-2-fluoro-4((1-(2-phenylpropan-2-yl)piperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
(R)-2,3-difluoro-4((1-(1-phenylethyl)piperidin-4yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
(R)-3-chloro-2-fluoro-4((1-(1-phenylethyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
4-((1-benzylpiperidin-4yl)oxy)-2-fluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
4-((1-benzylpiperidin-4-yl)oxy)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
3-chloro-4((1-(1-phenylcyclopropyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
5-chloro-4-(((3R,4S)-1-(3-(difluoromethyl)benzyl)-3-fluoropiperidin-4-yl)oxy)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(R)-5-chloro-2-fluoro-4((1-(1-phenylethyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
(R)-3-chloro-4-((1-(1-(5-chloro-2-fluorophenyl)ethyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
(R)-2,6-difluoro-4((1-(1-phenylethyl)piperidin-4yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
(R)-3-chloro-N-(isoxazol-3-yl)-4((1-(1-phenylethyl)piperidin-4-yl)oxy)benzenesulfonamide;
3-chloro-4((1-phenethylpiperidin-4-yl)oxy)-N-(thiazol-2-yl)benzenesulfonamide;
(R)-3-chloro-4-((1-(1-(2-fluoro-5-(trifluoromethyl)phenyl)ethyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
4-((1-benzylpiperidin-4-yl)oxy)-2,6-difluoro-3-methyl-N-(thiazol-2-yl)benzenesulfonamide;
4-((1-benzylpiperidin-4-yl)oxy)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide;
4-((cis-1-benzyl-2-methylpiperidin-4-yl)oxy)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide; and
4-((trans-1-benzyl-2-methylpiperidin-4-yl)oxy)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide;
(R)-3-chloro-4((1-(1-(5-cyclopropyl-2-fluorophenyl)ethyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
(R)-3-chloro-4((1-(1-(5-(difluoromethyl)-2-fluorophenyl)ethyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
(R)-3-chloro-2,6-difluoro-4-((1-(1-phenylethyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
3-chloro-4-((1-(3-(difluoromethyl)benzyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
(R)-5-chloro-2-fluoro-4-((1-(1-(2-fluoro-5-(trifluoromethyl)phenyl)ethyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
4-((1-benzylpiperidin-4yl)oxy)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(R)-2,6-difluoro-3-methyl-4-((1-(1-phenylethyl)piperidin-4-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
4-((1-benzylpiperidin-4-yl)oxy)-3-chloro-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide; and
4-((1-benzylpiperidin-4-yl)oxy)-2,6-difluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide.

### Claim 21 (depends on 18)

The compound of claim 18, wherein:
R1 is optionally substituted aryl or optionally substituted aralkyl;
R9 and R11 form an optionally substituted alkylene chain; and
R11 and R12 are each independently hydrogen or alkyl.

### Claim 22 (depends on 21)

The compound of claim 21 selected from:
4-((1R,3s,5S)-8-benzyl-8-azabicyclo[3.2.1]octan-3-yloxy)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide;
4-((1R,3r,5S)-8-benzyl-8-azabicyclo[3.2.1]octan-3-yloxy)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide;
4-(((1 R, 3s, 5S)-8-benzyl-8-azabicyclo[3.2.1]octan-3-yl)oxy)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;
5-chloro-4-(((1R,3s,5S)-8-(3-chlorobenzyl)-8-azabicyclo[3.2.1]octan-3-yl)oxy)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(((1R,3s,5S)-8-(5-chloro-2-fluorobenzyl)-8-azabicyclo[3.2.1]octan-3-yl)oxy)-N-(thiazol-4-yl)benzenesulfonamide;
4-(((1R, 3s, 5S)-8-benzyl-8-azabicyclo[3.2.1]octan-3-yl)oxy)-3-chloro-N-(thiazol-4-yl)benzenesulfonamide;
3-chloro-4-(((1R,3s,5S)-8-(3-chloro-4-fluorobenzyl)-8-azabicyclo[3.2.1]octan-3-yl)oxy) -N-(thiazol-4-yl)benzenesulfonamide; and
3-chloro-4-(((1R,3s,5S)-8-(3-(difluoromethyl)benzyl)-8-azabicyclo[3.2.1]octan-3-yl)oxy)-N-thiazol-4-yl)benzenesulfonamide.

### Claim 23 (depends on 16)

The compound of claim 16, wherein R2 is an optionally substituted 6-membered N-heteroaryl.

### Claim 24 (depends on 23)

The compound of claim 23, wherein R2 is optionally substituted pyridinyl or optionally substituted pyrimidinyl.

### Claim 25 (depends on 24)

The compound of claim 24 selected from:
(R)-3-chloro-4-((1-(1-phenylethyl)piperidin-4-yl)oxy)-N-(pyrimidin-4-yl)benzenesulfonamide;
(R)-3-chloro-N-(5-fluoropyrimidin-2-yl)-4-((1-(1-phenylethyl)piperidin-4-yl)oxy)benzenesulfonamide;
(S)-3-chloro-4-((1-(1-phenylethyl)piperidin-4-yl)oxy)-N-(pyrimidin-4-yl)benzenesulfonamide;
4-((1-benzylpiperidin-4-yl)oxy)-3-chloro-N-(6-fluoropyridin-2-yl)benzenesulfonamide; and
4-((1-benzylpiperidin-4-yl)oxy)-5-chloro-2-fluoro-N-(6-fluoropyridin-2-yl)benzenesulfonamide.

### Claim 26 (depends on 1)

The compound of claim 1, wherein R3 is —N(R13)—, wherein the compound has the following formula (Ib):
wherein m, n, X, Y, R1, R2, R4, R5, R6, R7, R8 and R13 are each as defined above in claim 1;
as an individual stereoisomer, enantiomer or tautomer thereof or a mixture thereof;
or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 27 (depends on 26)

The compound of claim 26, wherein:
n is 1 or 2;
m is 1 or 2;
X is a direct bond or —C(R9) R10—;
Y is a direct bond or —C(R11)R12—;
R1 is hydrogen, alkyl, —R17—OR 14, an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted aralkyl, an optionally substituted N-heterocyclyl, an optionally substituted N-heteroaryl, an optionally substituted O-heteroaryl or an optionally substituted S-heteroaryl;
R2 is an optionally substituted 5-membered N-heteroaryl or an optionally substituted 6-membered N-heteroaryl;
R4 and R5 are each independently hydrogen, alkyl or haloalkyl;
or R4 and R1, together with the carbon to which they are attached, form an optionally substituted cycloalkyl or an optionally substituted aryl, and R5, if present, if present, is hydrogen, alkyl, haloalkyl or optionally substituted aryl;
each R6 is independently hydrogen, alkyl, alkenyl, halo, haloalkyl, cyano, —OR14 or optionally substituted cycloalkyl;
R7 is halo, haloalkyl, cyano or —OR14;
each R8 is independently hydrogen, alkyl, halo, haloalkyl or —OR14;
or two R8's, together with the carbon to which they are both attached, may form an optionally substituted cycloalkyl;
R9, R10, R11 and R12 are each independently hydrogen, alkyl, haloalkyl, alkyl or —OR14;
or R9 and R11 form an optionally substituted alkylene chain and R10and R12 are as defined above; and
R13 is hydrogen, alkyl or haloalkyl;
each R14 are each independently hydrogen, alky, haloalkyl, optionally substituted aryl or optionally substituted aralkyl; and
R17 is a direct bond or an optionally substituted alkylene chain.

### Claim 28 (depends on 27)

The compound of claim 27, wherein X and Y are both a direct bond, wherein the compound has the following formula (Ib1):
wherein m, n, R1, R2, R4, R5, R6, R7, R8 and R13 are each as defined above in claim 27;
as an individual stereoisomer, enantiomer or tautomer thereof or a mixture thereof;
or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 29 (depends on 28)

The compound of claim 28, wherein R2 is an optionally substituted 5-membered N-heteroaryl.

### Claim 30 (depends on 29)

The compound of claim 29, wherein R2 is optionally substituted isoxazolyl, optionally substituted thiazolyl or optionally substituted thiadiazolyl.

### Claim 31 (depends on 30)

The compound of claim 30 selected from:
4-((1-benzyl-3-methylazetidin-3-yl)amino)-2,6-difluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide 2,2,2-trifluoroacetate;
4-((1-benzyl-3-methylazetidin-3-yl)amino)-2,6-difluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
4-((1-benzyl-3-methylazetidin-3-yl)amino)-3-chloro-N-(thiazol-4-yl)benzenesulfonamide;
4-((1-benzyl-3-methylazetidin-3-yl)amino)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide; and
4-((1-benzylazetidin-3-yl)amino)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide.

### Claim 32 (depends on 28)

The compound of claim 28, wherein R2 is an optionally substituted 6-membered N-heteroaryl.

### Claim 33 (depends on 32)

The compound of claim 32, wherein R2 is optionally substituted pyridinyl.

### Claim 34 (depends on 27)

The compound of claim 27, wherein X is —C(R9)R10—and Y is a direct bond, wherein the compound has the following formula (Ib2):
wherein m, n, R1, R2, R4, R5, R6, R7, R8, R9, R10and R13 are each as defined above in claim 27;
as an individual stereoisomer, enantiomer or tautomer thereof or a mixture thereof;
or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 35 (depends on 34)

The compound of claim 34, wherein R2 is an optionally substituted 5-membered N-heteroaryl.

### Claim 36 (depends on 35)

The compound of claim 35, wherein R2 is optionally substituted isoxazolyl, optionally substituted thiazolyl or optionally substituted thiadiazolyl.

### Claim 37 (depends on 36)

The compound of claim 36, wherein R2 is optionally substituted thiadiazolyl.

### Claim 38 (depends on 37)

The compound of claim 37 selected from:
(S)-3-chloro-4-((1-(3,5-difluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-3-chloro-4-((1-(2,5-difluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-4-(1-benzylpyrrolidin-3-yl)(methyl)amino)-2,6-difluoro-3-methyl-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-3-chloro-4-((1-(2,6-difluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-3-chloro-4-(1-(2-chlorobenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-2,6-difluoro-3-methyl-4-(methyl(1-((6-methylpyridin-2-yl)methyl)pyrrolidin-3-yl)amino)-N -(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-3-chloro-2,6-difluoro-4-(methyl(1-((6-methyl pyridin-2-methyl)pyrrolidin-3-yl)ami no)-N -(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-4(1-benzylpyrrolidin-3-yl)(methyl)amino)-2,6-difluoro-3-methyl-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-3-chloro-4-(ethyl(1-(3-methylbenzyl)pyrrolidin-3-yl)amino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-4-((1-benzylpyrrolidin-3-yl)(ethyl)amino)-3-chloro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-3-chloro-4-(methyl(1-(3-methylbenzyl)pyrrolidin-3-yl)amino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-4(1-benzylpyrrolidin-3-yl)(methyl)amino)-3-chloro-N-(1,2,4-thiadiazol-5- yl)benzenesulfonamide;
(R)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-3-chloro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-4-(1-benzylpyrrolidin-3-ylamino)-3-chloro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(R)-4-(1-benzylpyrrolidin-3-ylamino)-3-chloro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
4-(1-benzylpyrrolidin-3-ylamino)-3-chloro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-3-chloro-4((1-(3-chlorobenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(1,2,4-thiadiazol-5-l)benzenesulfonamide;
(S)-3-chloro-4-((1-(3-(difluoromethyl)benzyl)pyrrolidin-3-yl)(methyl)amino)-N-((1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-3-chloro-4((1-(3-chloro-2-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-3-chloro-4((1-(5-chloro-2-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;
(S)-3-chloro-4-((1-(2-fluoro-3-methylbenzyl)pyrrolidin-3-yI)(methyl)amino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide; and
(S)-3-chloro-4-((1-(2-fluoro-5-methylbenzyl)pyrrolidin-3-yI)(methyl)amino)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide.

### Claim 39 (depends on 36)

The compound of claim 36, wherein:
R1 is optionally substituted aryl or optionally substituted aralkyl; and
R2 is optionally substituted thiazolyl or isoxazolyl.

### Claim 40 (depends on 39)

The compound of claim 39 selected from:
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-5-bromo-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl) amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-(3-(2-hydroxypropan-2-yl)benzyl)pyrrolidin-3-yl)(methyl)amino)-N -(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4((1-(5-chloro-2-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-(2-fluoro-4-methylbenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-(3-phenylpropyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-(2-(difluoromethyl)benzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-4-((1-(2-hydroxybenzyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-4-((1-(3-hydroxybenzyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(R)-4-((1-benzylpyrrolidin-3-yl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1-(3-(difluoromethoxy)benzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-benzylpyrrolidin-3-yl)(methyl)amino)-5-cyclopropyl-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1-(2,5-dichlorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
5-chloro-2-fluoro-4-(methyl((S)-1-((R)-1-phenylpropyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-(4-propylbenzyl)pyrrolidin-3--yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-((1-(2-fluoro-5-methylbenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-benzylpyrrolidin-3-yl)(methyl)amino)-3-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(R)-4-((1-benzylpyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-(1-(3-(difluoromethyl)benzyl)pyrrolidin-3-yl)(methyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-(2-phenylpropan-2-yl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
3-chloro-4-(methyl((S)-1-((R)-1-phenylethyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-phenethylpyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4(1-benzylpyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(isothiazol-3-yl)-5-methylbenzenesulfonamide;
(S)-4(1-benzylpyrrolidin-3-yl)(methyl)amino)-2,6-difluoro-N-(isothiazol-3-yl)-3-methylbenzenesulfonamide;
(S)-2-fluoro-4-((1-(2-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-(1-benzylpyrrolidin-3-yl)(ethyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
methyl (S)-3-((3-((2-chloro-5-fluoro-4-(N-(thiazol-4yl)sulfamoyl)phenyl)(methyl)amino)pyrrolidin-1-yl)methyl)benzoate;
(S)-5-chloro-4(1-(2-chlorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1-(4-(dimethylamino)benzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-(1-benzylpyrrolidin-3-yl)(ethyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-(1-benzyl-3-methylpyrrolidin-3-yl)amino)-3-chloro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-3-chloro-4-(1-(5-chloro-2-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4(1-benzylpyrrolidin-3-yl)(methyl)amino)-5-bromo-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-4-((1-(3-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-(1-(2,5-difluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2,6-difluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-(1-benzylpyrrolidin-3-yl)(methyl)amino)-5-ethyl-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(1-(3-isopropoxybenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-(4-methylbenzyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1-(2,6-dimethylbenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-(3-fluoro-2-methylbenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-phenethylpyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4((1-(3-chloro-2-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-((1-(2-methoxybenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-(4-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
4-(((2R,3R)-1-benzyl-2-methylpyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
3-chloro-4-(methyl((S)-1-((S)-1-phenylethyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-(2,3-difluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-(2,3-difluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2,6-difluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2,6-difluoro-4-((1-(2-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-(3-(difluoromethyl)benzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-(2,5-difluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-benzylpyrrolidin-3-yl)(methyl)amino)-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1-(2,5-difluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4((1-(3-chlorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-3-chloro-4-((1-(2-fluoro-5-methylbenzyI)-3-methylpyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-2,5-difluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-4((1-(2-methoxybenzyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
4-(((3S,5S)-1-benzyl-5-methylpyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
5-chloro-4-(((S)-1((S)-1-(2-chlorophenyl)propyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1-(2-(difluoromethoxy)benzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-(4-fluoro-3-methylbenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
5-chloro-2-fluoro-4-(methyl((S)-1-((S)-1-phenylpropyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
4-((1-benzyl-3-methylpyrrolidin-3-yl)(methyl)amino)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide;
(S)-5-chloro-4-(1-(4-chlorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(R)-4-((1-benzylpyrrolidin-3yl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-(1-benzylpyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(isothiazol-4-yl)-5-methylbenzenesulfonamide;
(S)-2,6-difluoro-4-((1-(3-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(R)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-5-(difluoromethyl)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-(2-methylbenzyl)pyrrolidin-3-0amino)-N-(thiazol-4-y1)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-(2-hydroxybenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-(3-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1-(2,3-difluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-(3-(trifluoromethyl)benzyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-(2-fluoro-3-methylbenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-(2-fluoro-5-methoxybenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol -4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1-(3-(difluoromethyl)benzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(R)-4((1-benzyl-3-methylpyrrolidin-3-yl)amino)-3-chloro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-(2-methylbenzyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-4((1-(4-hydroxybenzyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-(1-benzylpyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)-3-(trifluoromethyl)benzenesulfonamide;
(S)-2-fluoro-4((1-(2-fluoro-3-methylbenzyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-benzylpyrrolidin-3-yl)(methyl)amino)-2-fluoro-3-methyl-N -(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-(4-bromobenzyl)pyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-(2-fluorobenzyl)pyrrolidin-3-l)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4(1-(3-methoxybenzyl)pyrrolidin-3-l)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4((1-(2-chloro-6-fluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-3-chloro-4-((1-(3-(difluoromethyl)benzyl)pyrrolidin-3-l)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((5-benzyl-5-azaspiro[2.4]heptan-7-amino)-5-chloro-2-fluoro-N-(thiazol-4yl)benzenesulfonamide;
(S)-4((5-benzyl-5-azaspiro[2.4]heptan-7-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-2,6-difluoro-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-3-chloro-2,6-difluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(R)-4-(1-benzylpyrrolidin-3-ylamino)-3-chloro-N-(thiazol-2-yl)bzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(1-(3-methylbenzyl)pyrrolidin-3-ylamino) N-(thiazol-2-yl)benzenesulfonamide;
(S)-4-(1-benzylpyrrolidin-3-ylamino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;
(R)-5-chloro-2-fluoro-4-(1-(3-methylbenzyl)pyrrolidin-3-ylamino) N(thiazol-2-yl)benzenesulfonamide;
(R)-4-(1-benzylpyrrolidin-3-ylamino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;
(S)-3-chloro-4((1-(3-chlorobenzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;
(S)-3-chloro-4-((1-(3-(difluoromethyl)benzyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide bis(trifluoroacetic acid) salt;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-3-chloro-N-(thiazol-4-yl)benzenesulfonamide;
3-chloro-4-(methyl((S)-1-((S)-1-phenylethyl)pyrrolidin-3-yl)amino)-N-(thiazol-2-yl)benzenesulfonamide;
3-chloro-4-(methyl((S)-1-((R)-1-phenylethyl)pyrrolidin-3-yl)amino)-N-(thiazol-2-yl)benzenesulfonamide;
4-((1-benzyl-3-methylpyrrolidin-3-yl) amino)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide;
(S)-3-chloro-4-(methyl(1-(2-phenylpropan-2-yl)pyrrodin-3yl) amino)-N-(thiazol-4-yl)benzenesulfonamide;
(R)-3-chloro-4-((1-(3-chlorobenzyl)pyrrolidin-3-yl)amino)-N-(thiazol-2-yl) benzenesulfonamide;
(R)-3-chloro-4-((1-(3-methylbenzyl)pyrrolidin-3-yl)amino)-N-(thiazol-2-yl) benzenesulfonamide;
(R)-3-chloro-4((1-(2-fluorobenzyl)pyrrolidin-3-yl)amino)-N-(thiazol-2-yl) benzenesulfonamide;
4-((trans-1-benzyl-4-methylpyrrolidin-3-yl)amino)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide;
4-((cis-1-benzyl-4-methylpyrrolidin-3-yl)amino)-3-chloro-N-(thiazol-2-yl)benzenesulfonamide; and
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(isoxazol-3-yl)-5-methylbenzenesulfonamide.

### Claim 41 (depends on 36)

The compound of claim 36, wherein:
R1 is an optionally substituted N-heterocyclyl, an optionally substituted N-heteroaryl, an optionally substituted O-heteroaryl or an optionally substituted S-heteroaryl; and
R2 is optionally substituted thiazolyl.

### Claim 42 (depends on 41)

The compound of claim 41 selected from:
(S)-4-((1-((1,4-dimethyl-1H-imidazol-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((4-methylthiazol-2yl)methyl)pyrrolidin-3-yl)amino)-N-(thiazol -4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-(pyridin-2-ylmethyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(14(1-((2,2,2-trifluoroethyl)-1H-pyrazol-5-methyl)pyrrolidin-3amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((2-methylthiazol-4-yl)methyl)pyrrolidin-3-yl)amino)-N-(thiazol -4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((1-methyl-1H-pyrazol-3-yl)methyl)pyrrolidin-3-yl)amino)-N -thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-4-((1((3-fluoro-6-methylpyridin-2yl)methyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl -(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-((1-benzyl-1H-pyrazol-4-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-5-chloro-2fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1((5-(trifluoromethyl)furan-2-methyl)pyrrolidin-3-yl)amino)-N-thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((2-methyloxazol-4-yl)methyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((5-methylfuran-2-methyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-4-((1((2-isopropyloxazol-4-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-((6-methoxypyridin-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-N-thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-((1-((3-fluoro-6-methylpyridin-2-methyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-(quinolin-8-ylmethyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((4-((4-cyclopropylthiazol-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-((6-(azetidin-1-yl)pyridin-2-methyl)pyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((2-phenylthiazol-4-yl)methyl)pyrrodin-3yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-(thiazol-2-ylmethyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((2-(trifluoromethyl)thiazol-4-yl)methyl)pyrrodin-3yl) amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1 -((2-cyclopropylthiazol-4-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((4-methyloxazol-2-yl)methyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-4- ((1-((3-isopropoxypyridin-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-4-((1((3-fluoro-6-methylpyridin-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4 ((1-((3-methoxypyridin-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-N-thiazol-4-yl)benzenesulfonamide;
(S)-4((1-((6-bromopyridin-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-((1H-pyrrol-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-y1)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-((5-methylfuran-2-yl)methyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl1)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-(thiazol-4-ylmethyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-((1, 5-dimethyl-1H-pyrazol-3-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl N-(thiazol-4-yl)benzenesulfonamide;
(S)-3-chloro-2,6-difluoro-4-(methyl(1-((6-methylpyridin-2-yl)methyl)pyrrolidin-3yl)-amino)-N-thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-((1-methyl-1H-pyrrol-2-yl)methyl)pyrrolidin-3-yl )amino)-N-thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-((1H-indol-3-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((5-(trifluoromethyl)furan-2-yl)methyl)pyrrodin-3yl) amino)-N-thiazol-4-yl benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-(oxazol-4-ylmethyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)methyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-4-(1-((3-methoxypyridin-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-((1-methyl-1H-pyrazol-3-yl)methyl)pyrrodin-3-yl) amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-((1-(imidazo[1,5-a]pyridin-3-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-N-thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-((2-(trifluoromethyl)pyridin-4-yl)methyl)pyrrodin-3yl) amino)-N-thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1((6-(difluoromethyl)pyridin-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4((1-(isoquinolin-8-ylmethyl)pyrrolidin-3-yl)(methyl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-((6-(trifluoromethyl)pyridin-2-yl)methyl)pyrrodin-3yl) amino)-N-thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-4-((1((2-isopropylthiazol-4-methyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-thiazol-4-yl)benzenesulfonamide;
(S)-4((1-(benzo[d]thiazol-2-ylmethyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((5-methylisothiazol-3-yl)methyl)pyrrolidin-3-yl)amino)-N-thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-(pyrazolo[1,5-a]pyridin-2-ylmethyl)pyrrolidin-3-yl)amino)-N-thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-((1H-indol-5-yl(methyl)pyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-(thiophen-2-ylmethyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1- ((4-methylpyridin-2-yl)methyl)pyrrolidin-3-yl)amino)-N-(thiazol -4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-((6-methylpyridin-2-yl)methyl)pyrrolidin-3-yl)amino)-N-(thiazol4-yl)benzenesulfonamide;
(S)-2-fluoro-4-((1((4-isopropylthiazol-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-5-methyl-N-thiazol-4-yl)benzenesulfonamide;
(S)-4((1((5-chlorothiazol-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1(1-(difluoromethyl)-1H-pyrazol-3-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2,6-difluoro-3-methyl-4-(methyl(1-((6-(trifluoromethyl)pyridin-2-yl)methyl)pyrrolidin-3-yl)-amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1((6-(difluoromethyl)-3-fluoropyridin-2-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1((5-methylthiophen-2-yl)methyl)pyrrolidin-3-yl)amino)-N-thiazol-4-benzenesulfonamide;
(S)-4((1-((1-(2,2-difluoroethyl)-1H-pyrazol-3-yl)methyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl (1-((2-methyl-5-(trifluoromethyl)oxazol-4-yl) methyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1((2,5-dimethyloxazol-4-yl)methyl)pyrrolidin-3-l)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-yl)methyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-((4-(trifluoromethyl)thiazol-2-yl)methyl)pyrrodin-3yl) amino)-N-(thiazol-4-benzenesulfonamide; and
(S)-2,6-difluoro-3-methyl-4-(methyl(1-((6-methylpyridin-2-yl)methyl)pyrrolidin-3-yl)amino)N-(thiazol-4-yl)benzenesulfonamide.

### Claim 43 (depends on 36)

The compound of claim 36, wherein:
R1 is hydrogen, alkyl, —R17—OR14 or an optionally substituted cycloalkyl; and
R4 and R5 are each independently hydrogen, alkyl or haloalkyl;
or R4 and R1, together with the carbon to which they are attached, form an optionally substituted cycloalkyl or an optionally substituted aryl, and R5, if present, if present, is hydrogen, alkyl, haloalkyl or optionally substituted aryl.

### Claim 44 (depends on 43)

The compound of claim 43 selected from:
2-fluoro-5-methyl-4-(methyl((S)-1-((1s,3R)-3-phenylcyclobutyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1-(2,3-dihydro-1H-inden-2-yl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-2-fluoro-4-(methyl(1-(1-phenylcyclopropyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4-((1-(2,3-dihydro-1H-inden-2-yl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-5-chloro-4-((1-(3,3-dimethylbutyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesolfunamide;
4-(((S)-1-((S)-2,3-dihydro-1H-inden-1-yl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesolfunamide;
(S)-5-chloro-2fluoro-4-((1-(1-(2fluorophenyl)cyclobutyl)pyrrolidin-3yl)(methyl)amino)-N-(thiazol-4-yl)benzenesolfunamide;
(S)-4((1-(2-(benzyloxy)ethyl)pyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
5-chloro-4-(((S)-1-((R)-2,3-dihydro-1H-inden-1-yl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
2-fluoro-5-methyl-4-(methyl((S)-1-((1r,3S)-3-phenylcyclobutyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-(cyclohexylmethyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide;
3-chloro-4-(((S)-1-((S)-2,3-dihydro-1H-inden-1-yl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
5-chloro-4-(((S)-1-((S)-2,3-dihydro-1H-inden-1yl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;
(S)-2-fluoro-5-methyl-4-(methyl(1-neopentylpyrrolidin-3-yl) amino)-N-(thiazol-4-yl)benzenesulfonamide; and
(S)-4((1-(3,3-dimethylbutyl)pyrrolidin-3-yl)(methyl)amino)-2-fluoro-5-methyl-N-(thiazol-4-yl)benzenesulfonamide.

### Claim 45 (depends on 34)

The compound of claim 34, wherein R2 is an optionally substituted 6-membered N-heteroaryl.

### Claim 46 (depends on 45)

The compound of claim 45, wherein R2 is optionally substituted pyridinyl.

### Claim 47 (depends on 46)

The compound of claim 46 selected from:
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-2,6-difluoro-N-(5-fluoropyridin-2-yl)-3-methylbenzenesulfonamide;
(S)-5-chloro-2-fluoro-N-(6-fluoropyridin-2-yl)-4-(methyl(1-(2-phenylpropan-2-yl)pyrrolidin-3-yl)amino)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-2,6-difluoro-N-(6-fluoropyridin-2-yl)-3-methylbenzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(5-fluoropyridin-2-yl)-5-methylbenzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-2-fluoro-N-(6-fluoropyridin-2-yl)-5-methylbenzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-N-(6-fluoropyridin-2-yl)benzenesulfonamide bis(trifluoroacetic acid) salt;
3-chloro-2-fluoro-N-(6-fluoropyridin-2-yl)-4-(((S)-1((S)-1-phenylethyl)pyrrolidin-3-yl)amino)benzenesulfonamide; and
5-chloro-2-fluoro-N-(6-fluoropyridin-2-yl)-4-(methyl((S)-1-((R)-1-phenylethyl)pyrrolidin-3-yl)amino)benzenesulfonamide.

### Claim 48 (depends on 27)

The compound of claim 27, wherein X is —C(R9)R10-and Y is —C(R11)R12—, wherein the compound has the following formula (Ib3):
wherein m, n, R1, R2, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each as defined above in claim 27;
as an individual stereoisomer, enantiomer or tautomer thereof or a mixture thereof;
or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 49 (depends on 48)

The compound of claim 48, wherein R2 is an optionally substituted 5-membered N-heteroaryl.

### Claim 50 (depends on 49)

The compound of claim 49, wherein R2 is optionally substituted isoxazolyl, optionally substituted thiazolyl or optionally substituted thiadiazolyl.

### Claim 51 (depends on 50)

The compound of claim 50 selected from:
(R)-5-chloro-2-fluoro-4-(methyl(1-(1-phenylethyl)piperidin-4-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
(R)-2-fluoro-5-methyl-4-(methyl(1-(1-phenylethyl)piperidin-4-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide;
4-((1-benzylpiperidin-4-yl)(methyl)amino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide; and 4-(1-benzylpiperidin-4-ylamino)-3-chloro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide.

### Claim 52 (depends on 48)

The compound of claim 48, wherein R2 is an optionally substituted 6-membered N-heteroaryl.

### Claim 53 (depends on 52)

The compound of claim 52, wherein R2 is optionally substituted pyridinyl.

### Claim 54 (depends on 1)

A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1, as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 55 (depends on 1)

A method of treating a disease or a condition associated with Nav1.6 activity in a mammal in need thereof, wherein the disease or condition is epilepsy and/or epileptic seizure disorder and wherein the method comprises administering to the mammal a therapeutically effective amount of a compound of claim 1, as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 56 (depends on 1)

A method of decreasing ion flux through Nav1.6 in a mammalian cell, wherein the method comprises contacting the cell with a compound of claim 1, as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 57 (depends on 1)

A method of selectively inhibiting a first voltage-gated sodium channel over a second voltage-gated sodium channel in a mammal, wherein the method comprises administering to the mammal a modulating amount of a compound of claim 1, as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 58 (depends on 57)

The method of claim 57, wherein the first voltage-gated sodium channel is Nav1.6.

### Claim 59 (depends on 58)

The method of claim 58, wherein the second voltage-gated sodium channel is Nav1.5.

### Claim 60 (depends on 58)

The method of claim 58, wherein the second voltage-gated sodium channel is Nav1.1.

### Claim 61

A compound selected from the group consisting of
(S)-4((1-(2,5-difluorobenzyl)pyrrolidin-3-yl)(methyl)amino)-3-methyl-N-(thiazol-4-yl)benzenesulfonamide;
(S)-4((1-benzylpyrrolidin-3-yl)(methyl)amino)-3-methyl-N-(thiazol-4-yl)benzenesulfonamide; and
(S)-5-chloro-2-fluoro-4-(methyl(1-(3-(trifluoromethyl)benzyl)pyrrolidin-3-yl)amino)-N-(thiazol-4-yl)benzenesulfonamide.

### Claim 62 (depends on 61)

A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 61, as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 63 (depends on 61)

A method of treating a disease or a condition associated with Nav1.6 activity in a mammal in need thereof, wherein the disease or condition is epilepsy and/or epileptic seizure disorder and wherein the method comprises administering to the mammal a therapeutically effective amount of a compound of claim 61, as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 64 (depends on 61)

A method of decreasing ion flux through Nav1.6 in a mammalian cell, wherein the method comprises contacting the cell with a compound of claims 61, as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 65 (depends on 61)

A method of selectively inhibiting a first voltage-gated sodium channel over a second voltage-gated sodium channel in a mammal, wherein the method comprises administering to the mammal a modulating amount of a compound of claims 61, as a stereoisomer, enantiomer or tautomer thereof or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

### Claim 66 (depends on 65)

The method of claim 65, wherein the first voltage-gated sodium channel is Nav1.6.

### Claim 67 (depends on 66)

The method of claim 66, wherein the second voltage-gated sodium channel is Nav1.5.

### Claim 68 (depends on 66)

The method of claim 66, wherein the second voltage-gated sodium channel is Nav1.1.