IP Library Granted Patent US 7,560,481
Granted Patent B2
US 7,560,481 · App. 11/315,862 · Granted Jul 14, 2009

Indoles are cannabinoid receptor ligands

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Quick Facts
Patent No.
US 7,560,481
App. No.
11/315,862
Granted
Jul 14, 2009
Kind
B2
Abstract

The present invention provides novel compounds of Formula (I) which are CB 2 selective ligands useful for the treatment of pain.

Claims (221)

1. A compound of Formula (I)

or a pharmaceutically acceptable salt thereof, wherein

R 1 is selected from the group consisting of alkoxyalkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylthioalkyl, arylalkyl, arylalkylcarbonyl, azidoalkyl, cycloalkylalkyl, cycloalkylalkylcarbonyl, haloalkyl, heteroarylalkyl, heteroarylalkylcarbonyl, heterocyclealkyl, heterocyclealkylcarbonyl, hydroxyalkyl, mercaptoalkyl, (NR A R B )carbonylalkyl, (NR A R B )sulfonylalkyl, (NR C R D )alkyl, -LOR 2 , -LSR 2 , -LS(O)R 2 , and -LS(O) 2 R 2 ;

L is alkylene;

R 2 is selected from the group consisting of alkyl, alkylcarbonyl, aryl, arylalkyl, carboxyalkenylcarbonyl, carboxyalkyl, carboxyalkylcarbonyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, (NR A R B )carbonylalkenylcarbonyl, (NR A R B )carbonylalkyl, and (NR A R B )carbonylalkylcarbonyl;

R 3 is selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, and haloalkyl;

R 4 is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cycloheptyl, and cyclooctyl, wherein the cyclopropyl, cyclobutyl, and cyclopentyl are substituted with 1, 2, 3, 4, 5, or 6 substituents selected from the group consisting of alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylthio, alkylthioalkyl, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, haloalkoxy, haloalkyl, halogen, hydroxy, hydroxyalkyl, mercapto, mercaptoalkyl, oxo, —NR E R F , (NR E R F )alkyl, (NR G R H )carbonyl, (NR G R H )carbonylalkyl, (NR G R H )sulfonyl, and (NR G R H )sulfonylalkyl, wherein the cycloheptyl and cyclooctyl are optionally substituted with 1, 2, 3, 4, 5, or 6 substituents selected from the group consisting of alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylthio, alkylthioalkyl, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, haloalkoxy, haloalkyl, halogen, hydroxy, hydroxyalkyl, mercapto, mercaptoalkyl, oxo, —NR E R F , (NR E R F )alkyl, (NR G R H )carbonyl, (NR G R H )carbonylalkyl, (NR G R H )sulfonyl, and (NR G R H )sulfonylalkyl;

R 5 , R 6 , R 7 , and R 8 are independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkoxy, alkoxycarbonylalkyl, alkoxysulfonyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylsulfinyl, alkylsulfinylalkyl, alkylsulfonyl, alkylsulfonylalkyl, alkylsulfonyloxy, alkylthio, alkylthioalkyl, alkynyl, aryl, arylalkoxy, arylalkyl, arylalkylthio, arylcarbonyl, aryloxy, aryloxyalkyl, arylthio, arylthioalkyl, carboxy, carboxyalkenyl, carboxyalkenylcarbonyl, carboxyalkenylcarbonyloxy, carboxy, carboxyalkyl, carboxyalkylcarbonyl, carboxyalkylcarbonyloxy, cyano, cyanoalkyl, cycloalkyl, cycloalkylalkoxy, cycloalkylalkyl, cycloalkylcarbonyl, cycloalkyloxy, cycloalkyloxyalkyl, haloalkoxy, haloalkyl, halogen, heteroaryl, heteroarylalkoxy, heteroarylalkyl, heteroaryloxy, heteroaryloxyalkyl, heterocycle, heterocyclealkoxy, heterocyclealkoxycarbonyl, heterocyclealkyl, heterocycleoxy, heterocycleoxyalkyl, hydroxy, hydroxyalkoxy, hydroxyalkyl, mercapto, mercaptoalkyl, nitro, —NR J R K , (NR J R K )alkoxy, (NR J R K )alkyl, (NR M R N )carbonyl, (NR M R N )carbonylalkyl, (NR M R N )sulfonyl, and (NR M R N )sulfonylalkyl;

R A , R B , R G , R H , R M , and R N are independently selected from the group consisting of hydrogen, alkenyl, alkoxyalkyl, alkoxycarbonylalkyl, alkyl, alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, and hydroxyalkyl; and

R C , R D , R E , R F , R J , R K , are independently selected from the group consisting of hydrogen, alkenyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkynyl, aryl, arylalkyl, arylsulfonyl, arylalkylsulfonyl, cycloalkyl, cycloalkylalkyl, cycloalkylsulfonyl, cycloalkylalkylsulfonyl, heteroaryl, heteroarylalkyl, heteroarylsulfonyl, heteroarylalkylsulfonyl, heterocycle, heterocyclealkyl, heterocyclesulfonyl, and heterocyclealkylsulfonyl.

2. A compound according to claim 1 wherein

R 1 is selected from the group consisting of alkoxyalkyl, alkylcarbonylalkyl, alkylthioalkyl, arylalkyl, azidoalkyl, cycloalkylalkyl, haloalkyl, heteroarylalkyl, heterocyclealkyl, heterocyclealkylcarbonyl, hydroxyalkyl, mercaptoalkyl, (NR A R B )carbonylalkyl, (NR A R B )sulfonylalkyl, (NR C R D )alkyl, and -LOR 2 ;

L is alkylene;

R 2 is selected from the group consisting of alkylcarbonyl, arylalkyl, and carboxyalkenylcarbonyl;

R 3 is selected from the group consisting of hydrogen and alkyl wherein the alkyl is methyl;

R 4 is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, and cycloheptyl, wherein the cyclopropyl, cyclobutyl, and cyclopentyl are substituted with 1, 2, 3, 4, 5, or 6 substituents selected from the group consisting of alkyl and halogen;

R 5 , R 6 , R 7 , and R 8 are independently selected from the group consisting of hydrogen, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkoxy, alkyl, alkylsulfonyl, arylalkoxy, carboxy, carboxyalkenylcarbonyloxy, carboxy, carboxyalkylcarbonyloxy, cyano, haloalkoxy, haloalkyl, halogen, heterocyclealkoxycarbonyl, hydroxy, hydroxyalkoxy, hydroxyalkyl, nitro, —NR J R K , (NR J R K )alkoxy, (NR J R K )alkyl, and (NR M R N )carbonyl;

R A , R B , R M , and R N are independently selected from the group consisting of hydrogen, alkoxycarbonylalkyl, alkyl, and hydroxyalkyl; and

R C , R D , R J , R K , are independently selected from the group consisting of hydrogen, alkoxycarbonyl, alkyl, and alkylsulfonyl.

3. A compound according to claim 1 wherein

R 3 is selected from the group consisting of hydrogen and alkyl wherein the alkyl is methyl; and

R 4 is 2,2,3,3-tetramethylcyclopropyl.

4. A compound according to claim 1 wherein

R 1 is heterocyclealkyl;

R 3 is selected from the group consisting of hydrogen and alkyl wherein the alkyl is methyl; and

R 4 is 2,2,3,3-tetramethylcyclopropyl.

5. A compound according to claim 1 wherein

R 1 is heteroarylalkyl;

R 3 is selected from the group consisting of hydrogen and alkyl wherein the alkyl is methyl; and

R 4 is 2,2,3,3-tetramethylcyclopropyl.

6. A compound according to claim 1 wherein

R 1 is arylalkyl;

R 3 is selected from the group consisting of hydrogen and alkyl wherein the alkyl is methyl; and

R 4 is 2,2,3,3-tetramethylcyclopropyl.

7. A compound according to claim 1 wherein

R 1 is selected from the group consisting of alkoxyalkyl, alkylcarbonylalkyl, alkylthioalkyl, azidoalkyl, cycloalkylalkyl, haloalkyl, heterocyclealkylcarbonyl, mercaptoalkyl, (NR A R B )carbonylalkyl, (NR A R B )sulfonylalkyl, (NR A R B )sulfonylalkyl, and (NR C R D )alkyl;

R 3 is selected from the group consisting of hydrogen and alkyl wherein the alkyl is methyl;

R 4 is 2,2,3,3-tetramethylcyclopropyl;

R A and R B are independently selected from the group consisting of hydrogen, alkoxycarbonylalkyl, alkyl, and hydroxyalkyl; and

R C and R D are independently selected from the group consisting of hydrogen, alkoxycarbonyl, alkyl, and alkylsulfonyl.

8. A compound according to claim 1 wherein

R 1 is -LOR 2 ;

R 2 is selected from the group consisting of alkylcarbonyl, arylalkyl, and carboxyalkenylcarbonyl;

R 3 is selected from the group consisting of hydrogen and alkyl wherein the alkyl is methyl;

R 4 is 2,2,3,3-tetramethylcyclopropyl; and

L is alkylene.

9. A compound according to claim 1 wherein

R 1 is hydroxyalkyl;

R 3 is selected from the group consisting of hydrogen and alkyl wherein the alkyl is methyl; and

R 4 is 2,2,3,3-tetramethylcyclopropyl.

10. A compound according to claim 1 wherein

R 1 is alkylthioalkyl;

R 3 is selected from the group consisting of hydrogen and alkyl wherein the alkyl is methyl; and

R 4 is 2,2,3,3-tetramethylcyclopropyl.

11. A compound according to claim 1 wherein

R 1 is heterocyclealkyl;

R 3 is selected from the group consisting of hydrogen and alkyl wherein the alkyl is methyl; and

R 4 is 2,2,3,3-tetrafluoro-1-methylcyclobutyl.

12. A compound according to claim 1 wherein

R 1 is heterocyclealkyl;

R 3 is selected from the group consisting of hydrogen and alkyl wherein the alkyl is methyl; and

R 4 is cycloheptyl.

13. A compound selected from the group consisting of

{1-[(1-methylpiperidin-2-yl)methyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(2-morpholin-4-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone p-toluenesulfonic acid;

[1-(2-pyridin-2-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone p-toluenesulfonic acid;

{1-[(1-methyl-1H-imidazol-2-yl)methyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone p-toluenesulfonic acid;

tert-butyl 4-(2-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}ethyl)piperidine-1-carboxylate;

[1-(2-Piperidin-4-yl-ethyl)-1H-indol-3-yl]-(2,2,3,3-tetramethyl-cyclopropyl)-methanone p-toluenesulfonic acid;

{1-[2-(1-methylpiperidin-4-yl)ethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone p-toluenesulfonic acid;

[1-(2-tetrahydro-2H-pyran-4-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(2-pyrrolidin-1-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone p-toluenesulfonic acid;

(2,2,3,3-tetramethylcyclopropyl)[1-(2-thien-2-ylethyl)-1H-indol-3-yl]methanone;

[1-(2-methoxyethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

1-(2-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}ethyl)pyrrolidin-2-one;

1-(2-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}ethyl)pyrrolidine-2,5-dione;

{1-[2-(4-methyl-1,3-thiazol-5-yl)ethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

{1-[2-(dimethylamino)ethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

(2,2,3,3-tetramethylcyclopropyl)[1-(2-thien-3-ylethyl)-1H-indol-3-yl]methanone;

{1-[2-(1-methylpyrrolidin-2-yl)ethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone p-toluenesulfonic acid;

[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(2-pyridin-3-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

{1-[2-(1H-pyrrol-1-yl)ethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

(1-{2-[4-(dimethylamino)phenyl]ethyl}-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(2-pyridin-4-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

{1-[4-(benzyloxy)butyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(4-hydroxybutyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(2-piperidin-1-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

{1-[4-(methylthio)butyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(3-morpholin-4-ylpropyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(2-azepan-1-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(2-piperazin-1-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone tris-trifluoroacetic acid;

{1-[2-(4-methylpiperazin-1-yl)ethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

3-(2-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}ethyl)-1,3-oxazolidin-2-one;

[1-(tetrahydrofuran-3-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

(2,2,3,3-tetramethylcyclopropyl)[1-(4,4,4-trifluorobutyl)-1H-indol-3-yl]methanone;

{1-[2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(3,4-dihydroxybutyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(1,3-dioxolan-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

{1-[2-(benzyloxy)ethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(2-hydroxyethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

{1-[3-(benzyloxy)propyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(3-hydroxypropyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

{1-[5-(benzyloxy)pentyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(5-hydroxypentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(3-methoxypropyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(tetrahydro-2H-pyran-4-ylacetyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

methyl 4-({3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}methyl)cyclohexanecarboxylate;

3-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}propanamide;

6-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}hexan-2-one;

{1-[(2R)-2,3-dihydroxypropyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[2-methyl-1-(2-morpholin-4-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(2-morpholin-4-ylethyl)-4-nitro-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[4-amino-1-(2-morpholin-4-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

cycloheptyl[1-(2-morpholin-4-ylethyl)-1H-indol-3-yl]methanone;

(2,2,3,3-tetrafluoro-1-methylcyclobutyl)[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl]methanone;

4-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}butyl acetate;

4-oxo-4-(4-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}butoxy)but-2-enoic acid;

[6-chloro-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

4-({3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}methyl)phenyl acetate;

[1-(4-hydroxybenzyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[6-(benzyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[6-hydroxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

4-oxo-4-({1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-6-yl}oxy)but-2-enoic acid;

[6-methoxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

{1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[5-(benzyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

(1-benzyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone;

[7-(benzyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(4-methoxybenzyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(3-methoxybenzyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[5-hydroxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(1,3-benzodioxol-5-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[7-hydroxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

4-oxo-4-({1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-7-yl}oxy)but-2-enoic acid;

[7-methoxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

methyl 1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-6-carboxylate;

1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-6-carboxylic acid;

{1-[(5-chloro-1,2,4-thiadiazol-3-yl)methyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

4-oxo-4-({1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-5-yl}oxy)but-2-enoic acid;

[1-(1,3-benzothiazol-2-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

ethyl 3-[({1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-6-yl}carbonyl)amino]propanoate;

[5-methoxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[4-(benzyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-6-carboxamide;

1-(2-morpholin-4-ylethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-7-carboxylic acid;

2-morpholin-4-ylethyl 1-(2-morpholin-4-ylethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-7-carboxylate;

[4-hydroxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[4-methoxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[6-methyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[6-(benzyloxy)-1-(2-morpholin-4-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[6-hydroxy-1-(2-morpholin-4-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[6-methoxy-1-(2-morpholin-4-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

4-oxo-4-({1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-5-yl}oxy)butanoic acid;

(2,2-dichloro-1-methylcyclopropyl)[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl]methanone;

[1-(4-azidobutyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(2-azidoethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

N-(4-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}butyl)methanesulfonamide;

ethyl 4-({1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-5-yl}oxy)butanoate;

[1-(3-azidopropyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

{1-[(2S)-tetrahydrofuran-2-ylmethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[5-(4-hydroxybutoxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[5-(4-bromobutoxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(5-azidopentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

N-(2-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}ethyl)methanesulfonamide;

methyl 1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxylate;

N-(3-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}propyl)methanesulfonamide;

N-(5-{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}pentyl)methanesulfonamide;

[5-(4-aminobutoxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[5-hydroxy-1-(2-morpholin-4-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

(2E)-4-({1-(2-morpholin-4-ylethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-5-yl}oxy)-4-oxobut-2-enoic acid;

[5-methoxy-1-(2-morpholin-4-ylethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

N-[4-({1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-5-yl}oxy)butyl]methanesulfonamide;

1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxamide;

N-(2-hydroxyethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxamide;

N-methyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxamide;

1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carbonitrile;

[5-(benzyloxy)-6-methoxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

N,N-dimethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxamide;

N-heptyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-5-carboxamide;

[5-hydroxy-6-methoxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

(2E)-4-({6-methoxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-5-yl}oxy)-4-oxobut-2-enoic acid;

{5-(benzyloxy)-1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[5-(aminomethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

{5-hydroxy-1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

N-({1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-5-yl}methyl)methanesulfonamide;

{5-(benzyloxy)-1-[4-(benzyloxy)butyl]-1H-indol-3-yl}(2,2,3,3-tetramethylcyclopropyl)methanone;

[6-(methylsulfonyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[5-hydroxy-1-(4-hydroxybutyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-6-carbonitrile;

[1-(tetrahydro-2H-pyran-4-ylmethyl)-6-(trifluoromethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[6-(aminomethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

N-({1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-6-yl}methyl)methanesulfonamide;

[5,6-dihydroxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

tetrahydro-2H-pyran-4-yl {3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}acetic acid;

ethyl tetrahydro-2H-pyran-4-yl{3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}acetate;

tert-butyl 1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-5-ylcarbamate;

[5-amino-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanonel;

[4,5,6,7-tetrafluoro-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

N-{1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-5-yl}methanesulfonamide;

[5-(hydroxymethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[5-(methoxymethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

3-(2-{5-hydroxy-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}ethyl)-1,3-oxazolidin-2-one;

3-(2-{5-(benzyloxy)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indol-1-yl}ethyl)-1,3-oxazolidin-2-one;

N-methyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-6-carboxamide;

N,N-dimethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-6-carboxamide;

N-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-3-[(2,2,3,3-tetramethylcyclopropyl)carbonyl]-1H-indole-6-carboxamide;

[1-(pyridin-3-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[1-(pyridin-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[5-bromo-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[5-(2-methoxyphenyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[5-phenyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[5-(3-methoxyphenyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[5-chloro-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[6-bromo-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[6-(2-methoxyphenyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[6-phenyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone;

[5-fluoro-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone; and

2-oxatricyclo[3.3.1.1˜3,7˜]dec-1-yl[1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-indol-3-yl]methanone.

14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I) of claim 1 or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable carrier.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 10, 2013
From: ABBOTT LABORATORIES
To: ABBVIE INC.
Reel/Frame 030185/0141 →
DOCUMENT RE-RECORDED TO CORRECT ERRORS CONTAINED IN PROPERTY NUMBER 11316862. DOCUMENT PREVIOUSLY RECORDED ON REEL 018416 FRAME 0693. (ASSIGNMENT OF ASSIGNOR'S INTEREST) OR NATURE OF CONVEYANCE Recorded Nov 13, 2006
From: FROST, JENNIFER M.; TIETJE, KARIN R.; DART, MICHAEL J.; MEYER, MICHAEL D.
To: ABBOTT LABORATORIES
Reel/Frame 018639/0165 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 20, 2006
From: FROST, JENNIFER M.; TIETJE, KARIN R.; DART, MICHAEL J.; MEYER, MICHAEL D.
To: ABBOTT LABORATORIES
Reel/Frame 018416/0693 →