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1. WO2016149169 - (INDAZOL-4-YL)HEXAHYDROPYRROLOPYRROLONES AND METHOD OF USE

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

WHAT IS CLAIMED IS:

1. A compound of formula (I):


or a pharmaceutically acceptable salt or isotopically labelled form thereof, wherein: one of Z1 and Z2 is NR1 and the other of Z1 and Z2 is CH2;

R1 is selected from the group consisting of -CH2G1, -CH2G2, -C(O)-G1, -C(O)-G2, -C(O)-R2, -C(O)N(Ra)-R2, -C(O)N(Ra)(Rb), -SO2-G1, -SO2-G2, -SO2-R2, -SO2N(Ra)-R2, and -SO2N(Ra)(Rb);

R2 is selected from the group consisting of C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, -(CR4aR5a)m-NO2, -(CR4aR5a)m-OR1a, -(CR4aR5a)m-OC(O)R1a, -(CR4aR5a)m-OC(O)N(Rb)(R3a), -(CR4aR5a)m-SR1a, -(CR4aR5a)m-S(O)2R2a, -(CR4aR5a)m-S(O)2N(Rb)(R3a), -(CR4aR5a)m-C(O)R1a, -(CR4aR5a)m-C(O)OR1a, -(CR4aR5a)m-C(O)N(Rb)(R3a), -(CR4aR5a)m-N(Rb)(R3a),

-(CR4aR5a) 1

m-N(Ra)C(O)R a, -(CR4aR5a)m-N(Ra)S(O)2R2a, -(CR4aR5a)m-N(Ra)C(O)O(R1a), -(CR4aR5a)m-N(Ra)C(O)N(Rb)(R3a), -(CR4aR5a)m-G1, -(CR4aR5a)m-G2, cyano-C1-C6-alkyl, and halo-C1-C6-alkyl;

Ra and Rb, at each occurrence, are each independently hydrogen, C1-C6-alkyl, or halo-C1-C6-alkyl;

Rc at each occurrence, is independently hydrogen, C1-C6-alkyl, aryl, aryl-C1-C6-alkyl, cycloalkyl, cycloalkyl-C1-C6-alkyl, or halo-C1-C6-alkyl; wherein said aryl, the aryl of aryl-C1-C6-alkyl, the cycloalkyl, and the cycloalkyl of cycloalkyl-C1-C6-alkyl are

independently unsubstituted or substituted with 1, 23, 4, or 5 substituents independently selected from the group consisting of C1-C6-alkyl, halo-C1-C6-alkyl, and halogen;

Rd at each occurrence, is independently C1-C6-alkyl or halo-C1-C6-alkyl;

R1a and R3a, at each occurrence, are each independently hydrogen, C1-C6-alkyl, halo-C1-C6-alkyl, -G1, or -(CR4aR5a)n-G1;

R2a, at each occurrence, is independently C1-C6-alkyl, halo-C1-C6-alkyl, -G1, or -(CR4aR5a)n-G1;

R4a and R5a, at each occurrence, are each independently hydrogen, halogen, C1-C6-alkyl, or halo-C1-C6-alkyl;

GAr is phenyl or a 6-membered heteroaryl; wherein GAr is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, cyano, halo-C1-C6-alkyl, and halogen;

G1 is aryl or heteroaryl; wherein G1 is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, cyano, halo-C1-C6-alkyl, halogen, nitro, -N(Rc)2, -N(Rc)C(O)Rc, -ORc, -C(O)Rc, -C(O)ORc, -C(O)N(Rc)2, -SO2Rd, -SO2N(Rc)2, and -CH2G3;

G2 is cycloalkyl, cycloalkenyl, or heterocycle; wherein G2 is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, cyano, halo-C1-C6-alkyl, halogen, nitro, oxo, -N(Rc)2, -N(Rc)C(O)Rc, -ORc, -C(O)Rc, -C(O)ORc, -C(O)N(Rc)2, -SO2Rd, and -SO2N(Rc)2;

G3 is aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl, wherein each G3 is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, halogen, cyano, oxo, -NO2, -OR1a, -OC(O)R1a, -OC(O)N(Rb)(R3a), -SR1a, -S(O)2R2a, -S(O)2N(Rb)(R3a), -C(O)R1a, -C(O)OR1a, -C(O)N(Rb)(R3a), -N(Rb)(R3a), -N(Ra)C(O)R1a, -N(Ra)S(O)2R2a,

-N(Ra)C(O)O(R1a), -N(Ra)C(O)N(Rb)(R3a), -(CR4aR5a)m-NO2, -(CR4aR5a)m-OR1a,

-(CR4aR5a)m-OC(O)R1a, -(CR4aR5a)m-OC(O)N(Rb)(R3a), -(CR4aR5a)m-SR1a,

-(CR4aR5a)m-S(O)2R2a, -(CR4aR5a)m-S(O)2N(Rb)(R3a), -(CR4aR5a)m-C(O)R1a,

-(CR4aR5a)m-C(O)OR1a, -(CR4aR5a)m-C(O)N(Rb)(R3a), -(CR4aR5a)m-N(Rb)(R3a),

-(CR4aR5a)m-N(Ra)C(O)R1a, -(CR4aR5a)m-N(Ra)S(O)2R2a, -(CR4aR5a)m-N(Ra)C(O)O(R1a), -(CR4aR5a)m-N(Ra)C(O)N(Rb)(R3a), cyano-C1-C6-alkyl, and halo-C1-C6-alkyl;

L1 is a bond or -CH2-; and

m and n, at each occurrence, are each independently 1, 2, 3, 4, or 5.

2. The compound of claim 1, wherein

Z1 is NR1; and

Z2 is CH2.

3. The compound of claim 2, wherein, R1 is selected from the group consisting of -CH2G1, -CH2G2, -SO2-G1, -SO2-G2, -SO2-R2, -SO2N(Ra)-R2, and -SO2N(Ra)(Rb).

4. The compound of claim 2, wherein, R1 is selected from the group consisting of -C(O)-G1, -C(O)-G2, -C(O)-R2, -C(O)N(Ra)-R2, and -C(O)N(Ra)(Rb).

5. The compound of claim 4, wherein,

R1 is -C(O)-G2;

G2 is cycloalkyl or heterocycle; wherein G2 is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of C1-C6-alkyl, cyano, halo-C1-C6-alkyl, halogen, and -ORc;

Rc at each occurrence, is independently hydrogen or C1-C6-alkyl;

GAr is phenyl; wherein GAr is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of C1-C6-alkyl, halo-C1-C6-alkyl, and halogen; and

L1 is a bond.

6. The compound of claim 4, wherein,

R1 is -C(O)-R2; and

R2 is selected from the group consisting of C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, -(CR4aR5a)m-OR1a, -(CR4aR5a)m-OC(O)R1a, -(CR4aR5a)m-C(O)R1a, -(CR4aR5a)m-C(O)OR1a, -(CR4aR5a)m-C(O)N(Rb)(R3a), and halo-C1-C6-alkyl.

7. The compound of claim 6, wherein,

R2 is C1-C6-alkyl or -(CR4aR5a)m-OR1a;

R1a is hydrogen or C1-C6-alkyl;

R4a and R5a, at each occurrence, are each independently hydrogen, C1-C6-alkyl, or halo-C1-C6-alkyl;

GAr is phenyl; wherein GAr is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of C1-C6-alkyl, halo-C1-C6-alkyl, and halogen;

L1 is a bond; and

m at each occurrence is independently 1, 2, 3 or 4.

8. The compound of claim 1, wherein,

Z1 is CH2; and

Z2 is NR1.

9. The compound of claim 8, wherein,

R1 is selected from the group consisting of -CH2G1 and -CH2G2.

10. The compound of claim 9, wherein,

R1 is -CH2G1;

Rc at each occurrence, is independently hydrogen or C1-C6-alkyl;

G1 is aryl or heteroaryl; wherein G1 is unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of C1-C6-alkyl, halo-C1-C6-alkyl, halogen, and -ORc;

GAr is phenyl; wherein GAr is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of C1-C6-alkyl, halo-C1-C6-alkyl, and halogen; and

L1 is a bond.

11. The compound of claim 8, wherein,

R1 is selected from the group consisting of -C(O)-G1, -C(O)-G2, -C(O)-R2,

-C(O)N(Ra)-R2, and -C(O)N(Ra)(Rb).

12. The compound of claim 11, wherein,

R1 is selected from the group consisting of -C(O)-G1, -C(O)-G2, -C(O)-R2,

-C(O)N(Ra)-R2, and -C(O)N(Ra)(Rb);

R2 is selected from the group consisting of C1-C6-alkyl, -(CR4aR5a)m-OR1a,

-(CR4aR5a)m-C(O)R1a, -(CR4aR5a)m-C(O)N(Rb)(R3a), -(CR4aR5a)m-N(Ra)C(O)R1a,

-(CR4aR5a) 1

m-G , -(CR4aR5a)m-G2, and halo-C1-C6-alkyl;

Ra and Rb, at each occurrence, are each independently hydrogen, C1-C6-alkyl, or halo-C1-C6-alkyl;

Rc at each occurrence, is independently hydrogen or C1-C6-alkyl;

R1a and R3a, at each occurrence, are each independently hydrogen, C1-C6-alkyl, or halo-C1-C6-alkyl;

R4a and R5a, at each occurrence, are each independently hydrogen or C1-C6-alkyl, or halo-C1-C6-alkyl;

G1 is aryl or heteroaryl; wherein G1 is unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of C1-C6-alkyl, halo-C1-C6-alkyl, halogen and -CH2G3;

G2 is cycloalkyl or heterocycle; wherein G2 is unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of C1-C6-alkyl, halo-C1-C6-alkyl, halogen, and -ORc;

G3 is aryl, heteroaryl, heterocycle, or cycloalkyl, wherein each G3 is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of C1-C6-alkyl, halogen, -OR1a, and halo-C1-C6-alkyl;

GAr is phenyl; wherein GAr is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of C1-C6-alkyl, halo-C1-C6-alkyl, and halogen; and

L1 is a bond; and

m, at each occurrence, is independently 1, 2, 3 or 4.

13. The compound of claim 8, wherein,

R1 is selected from the group consisting of -SO2-G1, -SO2-G2, -SO2-R2, -SO2N(Ra)-R2, and -SO2N(Ra)(Rb).

14. The compound of claim 13, wherein,

R1 is selected from the group consisting of -SO2-G1, -SO2-G2 and -SO2-R2;

R2 is selected from the group consisting of C1-C6-alkyl, -(CR4aR5a)m-OR1a,

-(CR4aR5a)m-C(O)R1a, -(CR4aR5a)m-G1, -(CR4aR5a)m-G2, and halo-C1-C6-alkyl;

Rc at each occurrence, is independently hydrogen or C1-C6-alkyl;

R1a, at each occurrence, are each independently hydrogen, C1-C6-alkyl, or

halo-C1-C6-alkyl;

R4a and R5a, at each occurrence, are each independently hydrogen, C1-C6-alkyl, or halo-C1-C6-alkyl;

G1 is aryl or heteroaryl; wherein G1 is unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of C1-C6-alkyl, halo-C1-C6-alkyl, and halogen;

G2 is cycloalkyl or heterocycle; wherein G2 is unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from the group consisting of C1-C6-alkyl,

halo-C1-C6-alkyl, halogen, -ORc, -C(O)Rc, and -C(O)ORc;

GAr is phenyl; wherein GAr is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of C1-C6-alkyl, halo-C1-C6-alkyl, and halogen;

L1 is a bond; and

m, at each occurrence, is independently 1, 2, 3 or 4.

15. The compound of claim 1, selected from:

(3aS,6aS)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-1-(3-hydroxy-3-methylbutanoyl)hexahydropyrrolo[3,4-b]pyrrol-6(1H)-one;

(3aR,6aR)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-1-(3-hydroxy-3-methylbutanoyl)hexahydropyrrolo[3,4-b]pyrrol-6(1H)-one;

(3aR*,6aR*)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-1-[(3R)-tetrahydrofuran-3-ylcarbonyl]hexahydropyrrolo[3,4-b]pyrrol-6(1H)-one;

rel-(3aR,6aR)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-1-(2-hydroxy-2-methylpropanoyl)hexahydropyrrolo[3,4-b]pyrrol-6(1H)-one;

rel-(3aR,6aR)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-1-[(1-hydroxycyclopropyl)carbonyl]hexahydropyrrolo[3,4-b]pyrrol-6(1H)-one;

rel-(3aR,6aR)-1-acetyl-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]hexahydropyrrolo[3,4-b]pyrrol-6(1H)-one;

(3aR*,6aR*)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-1-[(3R)-3-hydroxybutanoyl]hexahydropyrrolo[3,4-b]pyrrol-6(1H)-one;

rel-(3aR,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(3-methylbutanoyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

rel-(3aR,6aR)-5-benzyl-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

rel-(3aR,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(tetrahydrofuran-2-ylacetyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

rel-(3aR,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(3-hydroxybutanoyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

rel-(3aR,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(1H-imidazol-1-ylcarbonyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

rel-(3aR,6aR)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-N-(1,3-oxazol-5-ylmethyl)-4-oxohexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxamide;

rel-(3aR,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-[(5-methyl-1,2-oxazol-3-yl)carbonyl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

rel-(3aR,6aR)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-N,N-dimethyl-4-oxohexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxamide;

rel-(3aR,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(1,3-oxazol-4-ylcarbonyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

rel-(3aR,6aR)-5-acetyl-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

rel-(3aR,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(1,3-oxazol-2-ylmethyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

rel-(3aR,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-isobutyrylhexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aR,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-isobutyrylhexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(isobutylsulfonyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aR,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-[(2S)-tetrahydrofuran-2-ylacetyl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aS)-5-(ethylsulfonyl)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(isopropylsulfonyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aR,6aS)-5-(1-benzofuran-3-ylacetyl)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-[(3,3,3-trifluoropropyl)sulfonyl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(pyridin-3-ylsulfonyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aS)-5-(cyclopropylsulfonyl)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(phenylsulfonyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

tert-butyl 4-{[(3aS,6aS)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-4-oxohexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]sulfonyl}piperidine-1-carboxylate;

(3aR,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-{[2-(pyrrolidin-1-ylmethyl)-1,3-oxazol-4-yl]carbonyl}hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aR,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(tetrahydrofuran-3-ylcarbonyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aR,6aS)-5-[(3,5-dimethyl-1,2-oxazol-4-yl)acetyl]-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-[(3S)-3-hydroxybutanoyl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(3-hydroxy-3-methylbutanoyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aR,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-[(3S)-3-hydroxybutanoyl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aR,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(3-hydroxy-3-methylbutanoyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-[(3R)-3-hydroxybutanoyl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aR,6aS)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-[(3R)-3-hydroxybutanoyl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aR,6aS)-5-[(2,2-difluorocyclopropyl)carbonyl]-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(2-hydroxy-2-methylpropanoyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-[(1-hydroxycyclopropyl)carbonyl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aR)-5-[(3-chlorocyclobutyl)carbonyl]-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

3-[(3aR,6aS)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-4-oxohexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]-3-oxopropanamide;

(3aS,6aR)-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]-5-(3-hydroxypropanoyl)hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aS,6aR)-5-acetyl-2-[1-(2-fluorophenyl)-1H-indazol-4-yl]hexahydropyrrolo[3,4-c]pyrrol-1(2H)-one;

(3aR,6aR)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-1-(2-hydroxy-2-methylpropanoyl)hexahydropyrrolo[3,4-b]pyrrol-6(1H)-one;

(3aR,6aR)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-1-[(1-hydroxycyclopropyl)carbonyl]hexahydropyrrolo[3,4-b]pyrrol-6(1H)-one; and

(3aS,6aS)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-1-(2-hydroxy-2-methylpropanoyl)hexahydropyrrolo[3,4-b]pyrrol-6(1H)-one.

16. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically acceptable carrier.

17. A method of selectively modulating the effects of pain in a mammal comprising administering an effective amount of a compound of claim 1.

18. A method of treating a condition or disorder modulated by the voltage-gated sodium channels Nav1.7 and/or Nav1.8 in a mammal comprising administering an effective amount of a compound of claim 1.

19. The method according to claim 18, wherein the condition or disorder is selected from the group consisting of pain, including osteoarthritis pain, joint pain (knee pain), neuropathic pain, post-surgical pain, low back pain, and diabetic neuropathy, pain during surgery, cancer pain, chemotherapy induced pain, headaches, including cluster headache, tension headache, migraine pain, trigeminal neuralgia, shingles pain, post-herpetic neuralgia, carpal tunnel syndrome, inflammatory pain, pain from rheumatoid arthritis, colitis, pain of interstitial cystitis, visceral pain, pain from kidney stone, pain from gallstone, angina, fibromyalgia, chronic pain syndrome, thalamic pain syndrome, pain from stroke, phantom limb pain, sunburn, radiculopathy, complex regional pain syndrome, HIV sensory neuropathy, central neuropathic pain syndromes, multiple sclerosis pain, Parkinson disease pain, spinal cord injury pain, menstrual pain, toothache, pain from bone metastasis, pain from endometriosis, pain from uterine fibroids, nociceptive pain, hyperalgesia, temporomandibular joint pain, inherited erythromelalgia (IEM), and paroxysmal extreme pain disorder (PEPD).