IP Library Granted Patent US 7,304,081
Granted Patent B2
US 7,304,081 · App. 11/122,309 · Granted Dec 4, 2007

Amido compounds and their use as pharmaceuticals

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Quick Facts
Patent No.
US 7,304,081
App. No.
11/122,309
Granted
Dec 4, 2007
Kind
B2
Abstract

The present invention relates to inhibitors of 11-β hydroxyl steroid dehydrogenase type 1, antagonists of the mineralocorticoid receptor (MR), and pharmaceutical compositions thereof. The compounds of the invention can be useful in the treatment of various diseases associated with expression or activity of 11-β hydroxyl steroid dehydrogenase type 1 and/or diseases associated with aldosterone excess.

Claims (293)

1. A compound having Formula Va:

or pharmaceutically acceptable salt or prodrug thereof, wherein:

ring B is a fused phenyl group;

Q 1 is O;

Q 2 is CO;

Cy is aryl or cycloalkyl, each optionally substituted by 1, 2, 3, 4 or 5 —W—X—Y—Z;

R 1 and R 2 together with the C atom to which they are attached form a 3-, 4-, 5-, 6- or 7-membered cycloalkyl group optionally substituted by 1, 2 or 3 R 5 ;

R 5 is halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;

W, W′ and W″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, CS, COO, CONR e , OCONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl are each optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;

X, X′ and X″ are each, independently, absent, C 1-8 alkylenyl, C 2-8 alkenylenyl, C 2-8 alkynylenyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocycloalkylalkyl, arylalkenyl, cycloalkylalkenyl, heteroarylalkenyl, heterocycloalkylalkenyl, arylalkynyl, cycloalkylalkynyl, heteroarylalkynyl, heterocycloalkylalkynyl, each of which is optionally substituted by one or more halo, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;

Y, Y′ and Y″ are each, independently, absent, C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl, O, S, NR e , CO, CS, COO, CONR e , OCONR e , SO, SO 2 , SONR e , or NR e CONR f , wherein said C 1-6 alkylenyl, C 2-6 alkenylenyl, C 2-6 alkynylenyl are each optionally substituted by 1, 2 or 3 halo, OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino;

Z, Z′ and Z″ are each, independently, H, halo, oxo, sulfido, CN, NO 2 , OH, C 1-4 alkoxy, C 1-4 haloalkoxy, amino, C 1-4 alkylamino or C 2-8 dialkylamino, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl is optionally substituted by 1, 2 or 3 halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R d , NR c C(O)OR a , S(O)R b , S(O)NR c R d , S(O) 2 R b , or S(O) 2 NR c R d ;

wherein two —W—X—Y—Z attached to the same atom optionally form a 3-20 membered cycloalkyl or heterocycloalkyl group optionally substituted by 1, 2 or 3 —W″—X″—Y″—Z″;

wherein —W—X—Y—Z is other than H;

wherein —W″—X″—Y″—Z″ is other than H;

R a is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, (C 1-6 alkoxy)-C 1-6 alkyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl or heterocycloalkyl;

R b is H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl;

R c and R d are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;

or R c and R d together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;

R e and R f are each, independently, H, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, aryl, cycloalkyl, arylalkyl, or cycloalkylalkyl;

or R e and R f together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;

q is 0;

v is 0, 1 or 2;

r is 0, 1 or 2;

s is 0, 1 or 2; and

the sum of r and s is 0, 1 or 2.

2. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Cy is aryl optionally substituted by 1, 2, 3, 4 or 5 —W—X—Y—Z.

3. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Cy is aryl optionally substituted by 1, 2 or 3 halo, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, or C 1-4 haloalkoxy.

4. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Cy is aryl optionally substituted by 1, 2 or 3 halo, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, or C 1-4 haloalkoxy.

5. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R 1 and R 2 together with the C atom to which they are attached form a cyclopropyl group.

6. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein —W—X—Y—Z is halo, cyano, C 1-4 cyanoalkyl, nitro, C 1-8 alkyl, C 2-8 alkenyl, C 1-8 haloalkyl, C 1-4 alkylthio, C 1-4 haloalkylthio, C 1-8 alkoxy, C 2-8 alkenyloxy, C 1-4 haloalkoxy, OH, (C 1-4 alkoxy)-C 1-4 alkyl, amino, C 1-4 alkylamino, C 2-8 dialkylamino, OC(O)NR c R d , NR c C(O)R d , NR c C(O)OR a , NR c S(O) 2 R d , C(O)OR a , C(O)R a , C(O)NR a NR c R d , S(O) 2 R d , SR d , C(O)NR c R d , C(S)NR c R d , aryloxy, heteroaryloxy, cycloalkyloxy, cycloalkenyloxy, heterocycloalkyloxy, arylalkyloxy, heteroarylalkyloxy, cycloalkylalkyloxy, heterocycloalkylalkyloxy, heteroaryloxyalkyl, aryloxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, cycloalkylalkyl, or heterocycloalkylalkyl;

wherein each of said C 1-8 alkyl, C 2-8 alkenyl, C 1-8 haloalkyl, C 1-4 alkylthio, C 1-4 haloalkylthio, C 1-8 alkoxy, aryloxy, heteroaryloxy, arylalkyloxy, heteroarylalkyloxy, heteroaryloxyalkyl, aryloxy, heteroaryloxy, cycloalkyloxy, cycloalkenyloxy, heterocycloalkyloxy, arylalkyloxy, heteroarylalkyloxy, cycloalkylalkyloxy, heterocycloalkylalkyloxy, heteroaryloxyalkyl, aryloxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted by 1, 2, or 3 halo, cyano, nitro, hydroxyl-(C 1-6 alkyl), aminoalkyl, dialkylaminoalkyl, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, OH, OR a , (C 1-4 alkoxy)-C 1-4 alkyl, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C(O)NR c R d , C(O)OR a , C(O)R a , (cyclocalkylalkyl)-C(O)—, NR c C(O)R d , NR c C(O)OR a , NR c S(O) 2 R d , C(S)NR c R d , S(O) 2 R d , SR d , (C 1-4 alkyl)sulfonyl, arylsulfonyl, aryl optionally substituted by halo, heteroaryl, cycloalkylalkyl, cycloalkyl, or heterocycloalkyl.

7. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein W—X—Y—Z is halo, cyano, C 1-4 cyanoalkyl, nitro, C 1-8 alkyl, C 1-8 alkenyl, C 1-8 haloalkyl, C 1-10 alkoxy, C 1-4 haloalkoxy, OH, C 1-8 alkoxyalkyl, amino, C 1-4 alkylamino, C 2-8 dialkylamino, OC(O)NR c R d , NR c C(O)R d , NR c C(O)OR a , aryloxy, heteroaryloxy, arylalkyloxy, heteroarylalkyloxy, heteroaryloxyalkyl, aryloxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, cycloalkylalkyl, or heterocycloalkylalkyl;

wherein each of said C 1-8 alkyl, C 1-8 alkenyl, C 1-8 haloalkyl, C 1-8 alkoxy, aryloxy, heteroaryloxy, arylalkyloxy, heteroarylalkyloxy, heteroaryloxyalkyl, aryloxyalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted by 1, 2, or 3 halo, cyano, nitro, hydroxyl-(C 1-6 alkyl), aminoalkyl, dialkylaminoalkyl, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, OH, C 1-8 alkoxyalkyl, amino, C 1-4 alkylamino, C 2-8 dialkylamino, C(O)NR c R d , C(O)OR a , NR c C(O)R d , NR c S(O) 2 R d , (C 1-4 alkyl)sulfonyl, arylsulfonyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl.

8. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein —W—X—Y—Z is halo, cyano, C 1-4 cyanoalkyl, nitro, C 1-4 nitroalkyl, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, OH, (C 1-4 alkoxy)-C 1-4 alkyl, amino, C 1-4 alkylamino, C 2-8 dialkylamino, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl.

9. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein —W—X—Y—Z is halo, C 1-4 alkyl, or C 1-4 alkoxy.

10. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein:

—W—X′—Y′—Z′ is halo, OH, cyano, CHO, COOH, C(O)O—(C 1-4 alkyl), C(O)—(C 1-4 alkyl), SO 2 —(C 1-4 alkyl), C 1-4 alkyl, C 1-4 alkoxy or —L—R 7 , wherein said C 1-4 alkyl or C 1-4 alkoxy is optionally substituted by one or more halo, OH, COOH or C(O)O—(C 1-4 alkyl);

L is absent, O, CH 2 , NHSO 2 , N[C(O)—(C 1-4 alkyl)]; and

R 7 is aryl or heteroaryl, each is optionally substituted by 1, 2, or 3 halo, OH, cyano, CHO, COOH, C(O)O—(C 1-4 alkyl), C(O)—(C 1-4 alkyl), SO 2 —(C 1-4 alkyl), SO 2 —NH(C 1-4 alkyl), C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haoalkyl, C 1-4 hydroxyalkyl, aryl, heteroaryl or aryloxy.

11. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein —W′—X′—Y′—Z′ is halo; C 1-4 alkyl; C 1-4 haloalkyl; OH; C 1-4 alkoxy; C 1-4 haloalkoxy; hydroxyalkyl; alkoxyalkyl; aryl; heteroaryl; aryl substituted by halo, C 1-4 alkyl, C 1-4 alkoxy, aryl, heteroaryl, or aryloxy; or heteroaryl substituted by halo, C 1-4 alkyl, C 1-4 alkoxy, aryl, or heteroaryl.

12. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein —W″—X″—Y″—Z″ is halo, cyano, C 1-4 cyanoalkyl, nitro, C 1-4 nitroalkyl, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, OH, (C 1-4 alkoxy)-C 1-4 alkyl, amino, C 1-4 alkylamino, C 2-8 dialkylamino, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl.

13. A compound of claim 1 having Formula VII:

wherein Q 3 and Q 4 are both CH.

14. A compound of claim 13 having Formula VIII:

15. A compound of claim 1 selected from:

1′-{[1-(4-Chlorophenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1-({1-[4-(Pyridin-2-yloxy)phenyl]cyclopropyl}carbonyl)-3H-spirol[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Chlorophenyl)cyclobutyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one; 1′-{[1-(4-Methylphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Methoxyphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(2,4-Dichlorophenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Chlorophenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidine];

1′-{[1-(6-Phenylpyridin-3-yl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one; and

1′-{[1-(4-Pyrrolidin-1-ylphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

or pharmaceutically acceptable salt thereof.

16. A compound of claim 1 selected from:

1′-{[1-(6-Pyrrolidin-1-ylpyridin-3-yl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Oxo-1,3-oxazolidin-3-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Oxopyrrolidin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(Pyridin-4-ylmethoxy)phenyl]cyclopropyl}-carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(Pyridin-2-ylmethoxy)phenyl]cyclopropyl}-carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Pyridin-4-ylphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Cyclopropylphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(2-Fluoro-4-pyridin-2-ylphenyl)cyclopropyl]-carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[(E)-2-(4-Methylphenyl)vinyl]phenyl}-cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Pyridin-2-ylethoxy)phenyl]cyclopropyl}-carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[(E)-2-Pyridin-4-ylvinyl]phenyl}cyclopropyl)-carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(3,5-Dimethylisoxazol-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(1-Methyl-1H-pyrazol-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4′-(Methylsulfonyl)biphenyl-4-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(1H-1,2,4-Triazol-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(1-Hydroxycyclopentyl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(1-Hydroxycyclobutyl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(4-Hydroxytetrahydro-2H-pyran-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Amino-1,3-thiazol-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Methyl-1,3-thiazol-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Ethyl-1,3-thiazol-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(1,3-Thiazol-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[trans-1-(4-Chlorophenyl)-3-hydroxycyclobutyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[cis-1-(4-Chlorophenyl)-3-fluorocyclobutyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Oxo-1,3-oxazolidin-3-yl)phenyl]cyclobutyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-Pyridin-4-ylcyclobutyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Pyridin-4-ylphenyl)cyclobutyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N,N-Dimethyl-4-[5-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)pyridin-2-yl]piperazine-1-carboxamide;

1′-[(1-{6-[4-(Methylsulfonyl)piperazin-1-yl]pyridin-3-yl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{6-[4-(2-Fluorophenyl)piperazin-1-yl]pyridin-3-yl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(3,3-Difluoropyrrolidin-1-yl)pyridin-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{6-[3-Hydroxypyrrolidin-1-yl]pyridin-3-yl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N-{1-[5-(1-{[3-Oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)pyridin-2-yl]pyrrolidin-3-yl}acetamide;

1′-({1-[6-(1,3-Dihydro-2H-isoindol-2-yl)pyridin-3-yl]cyclo-propyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(3,4-Dihydro-isoquinolin-2(1H)-yl)pyridin-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(6-Morpholin-4-ylpyridin-3-yl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(4-Hydroxypiperidin-1-yl)pyridin-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N-{4-[5-(1-{[3-Oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)pyridin-2-yl]phenyl}acetamide;

1′-({1-[6-(2-Fluorophenyl)pyridin-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(1-Benzothien-3-yl)pyridin-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(2,3′-Bipyridin-5-yl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(1-Methyl-1H-indol-5-yl)pyridine-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{6-[3-(Trifluoromethoxy)phenyl]pyridine-3-yl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(3-Thienyl)pyridine-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{6-[3-(Trifluoromethyl)phenyl]pyridine-3-yl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(1-Methyl-1H-pyrazol-4-yl)pyridine-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(6-Chloropyridin-3-yl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(Benzyloxy)pyridin-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-Quinolin-3-ylcyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

or pharmaceutically acceptable salt thereof.

17. A compound of claim 1 selected from:

4-(1-{[3-Oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)benzonitrile;

1′-{[1-(3-(Hydroxymethyl)phenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Bromophenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(Pyrrolidin-1-ylcarbonyl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

4-(1-{[3-Oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)benzohydrazide;

N-Methyl-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)benzamide;

4-(1-{[3-Oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)benzenecarbothioamide;

1′-[(1-{4-[2-(Trifluoromethyl)-1H-imidazol-4-yl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(1-Methyl-1H-pyrazol-3-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N-Cyclopropyl-4′-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)biphenyl-4-carboxamide;

1′-[(1-{4-[5-(Trifluoromethyl)-1H-1,2,4-triazol-3-yl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(1-Methyl-1H-tetrazol-5-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Amino-1,3-oxazol-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Pyrimidin-5-ylphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(6-Fluoropyridin-3-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(6-Pyrrolidin-1-ylpyridin-3-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N-Cyclopropyl-5-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]pyridine-2-carboxamide;

N-Methyl-5-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]pyridine-2-carboxamide;

1′-({1-[4-(Methylsulfonyl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[(Trifluoromethyl)thio]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Chloro-2-fluorophenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Oxopyridin-1(2H)-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

Methyl 4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]piperazine-1-carboxylate;

1′-[(1-{4-[4-(Methylsulfonyl)-2-oxopiperazin-1-yl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

7-Fluoro-1′-[(1-{4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}cyclopropyl)carbonyl]spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N-[4-(1-{[3-Oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]cyclopropanecarboxamide;

N-[4-(1-{[3-Oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]benzenesulfonamide;

Methyl allyl[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]carbamate;

1′-({1-[4-(1H-1,2,4-Triazol-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-Quinolin-6-ylcyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-Pyridin-4-ylcyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-Quinolin-4-ylcyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-Quinolin-2-ylcyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-Pyridin-2-ylcyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(1,3-Benzothiazol-2-yl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(Pyrrolidin-1-ylmethyl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

[4-(1-{[3-Oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]cyclopropyl acetic acid;

1′-({1-[4-(3-Thienyl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(2-Fluoro-4-pyridin-4-ylphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

5-Methoxy-1′-{[1-(4-methylphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Methylphenyl)cyclopropyl]carbonyl}-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine]-5-carbonitrile;

1′-({1-[3′-(Hydroxymethyl)biphenyl-4-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one; and

1′-({1-[2′-(Methylthio)biphenyl-4-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

or pharmaceutically acceptable salt thereof.

18. A compound of claim 1 selected from:

1′-({1-[4-(2-Oxoimidazolidin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[4-Isopropyl-2-oxo-1,3-oxazolidin-3-yl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[2-Fluoro-4-(2-oxopyrrolidin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[2-Fluoro-4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

Methyl 3-oxo-4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1-yl]carbonyl}cyclopropyl)phenyl]piperazine-1-carboxylate;

1′-[(1-{6-[4-(Cyclopropyl carbonyl)piperazin-1-yl]pyridin-3-yl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{6-[4-(Pyridin-4-yloxy)piperidin-1-yl]pyridin-3-yl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{6-[3-(Pyridin-4-yloxy)pyrrolidin-1-yl]pyridin-3-yl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(6-Methoxypyridin-3-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

[4′-(1-{[3-Oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)biphenyl-3-yl]acetonitrile;

1′-({1-[4-(6-Aminopyridin-3-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(6-Hydroxypyridin-3-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1 ′-({1-[4-(5-Methylpyridin-2-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[(Pyridin-2-yloxy)methyl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[(Pyridin-3-yloxy)methyl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[(Pyridin-4-yloxy)methyl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

3-(1-{[3-Oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)benzonitrile;

1′-[(1-Biphenyl-3-ylcyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(1-Naphthyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one

1′-[(1-Quinolin-6-ylcyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[(5-Methylisoxazol-3-yl)methoxy]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Pyridin-3-yl-1,3-thiazol-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[5-(Trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-tert-Butyl-1,3-thiazol-2-yl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(4-Chlorophenyl)-1,3-thiazol-2-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′,1″-[1,4-Phenylenebis(cyclopropane-1,1-diylcarbonyl)]bis(3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one);

1′-[(1-Pyridin-3-ylcyclobutyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Chlorophenyl)cyclobutyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

or pharmaceutically acceptable salt thereof.

19. A compound of claim 1 selected from:

Ethyl 4-[5-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)pyridin-2-yl]piperazine-1-carboxylate;

1′-[(1-{6-[4-(ethylsulfonyl)piperazin-1-yl]pyridin-3-yl}cyclopropyl)carbonyl]-3H-spiro-[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(4-Methylpiperazin-1-yl)pyridin-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(4-Phenylpiperazin-1-yl)pyridin-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{6-[4-(3-Methylbutanoyl)piperazin-1-yl]pyridin-3-yl}cyclopropylcarbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{6-[4-(Cyclopropylmethyl)piperazin-1-yl]pyridin-3-yl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(2,5-Dihydro-1H-pyrrol-1-yl)pyridin-3-yl]cyclopropyl}carbonyl)-3-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(6-Piperidin-1-ylpyridin-3-yl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(4-Methyl-2-oxopiperazin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(4-Acetyl-2-oxo-piperazin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

tert-Butyl 4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]piperazine-1-carboxylate;

1′-({1-[4-(4-Isobutyrylpiperazin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[4-(Cyclopropyl carbonyl)piperazin-1-yl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[4-(Methylsulfonyl)piperazin-1-yl]phenyl}cyclopropyl carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(4-Methylpiperazin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N-Methyl-N-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]cyclopropanecarboxamide;

N-[4-(1-{[3-Oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]acetamide;

1′-({1-[4-(2-Oxopyrrolidin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Oxo-1,3-oxazolidin-3-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(1H-Pyrazol-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Oxopiperidin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

2-Methyl-3-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]imidazolidine-2,4-dione;

1′-{[1-(4-Morpholin-4-ylphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-Pyridin-3-ylcyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N-Methyl-4-[5-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)pyridin-2-yl]benzamide;

N,N-Dimethyl-4-[5-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)pyridin-2-yl]benzamide;

1′-[(1-{6-[4-(Methylsulfonyl)phenyl]pyridin-3-yl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-{[1-(4-Methoxyphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(Pyridin-2-yloxy)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(Pyridin-3-ylmethoxy)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(Isoquinolin-1-ylmethoxy)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

Methyl 4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]-3,6-dihydropyridine-(2H)-carboxylate;

Ethyl 4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate;

1′-({1-[4-(1-Acetyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[1-(3-Methylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

5-Hydroxy-1′-{[1-(4-methylphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one; and

1′-({1-[4-(Pyrrolidin-1-ylmethyl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

or pharmaceutically acceptable salt thereof.

20. A compound of claim 1 selected from:

1′-{[1-(4-Chlorophenyl)cyclo-pentyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

Methyl 4-[5-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)pyridin-2-yl]piperazine-1-carboxylate;

N,N-Dimethyl-4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclo-propyl)phenyl]piperazine-1-carboxamide;

Methyl 4-[3-fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclo-propyl)phenyl]piperazine-1-carboxylate;

1′-({1-[2-Fluoro-4-(4-propionylpiperazin-1-yl)phenyl]cyclo-propyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[2-Fluoro-4-(4-isobutyrylpiperazin-1-yl)phenyl]cyclo-propyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[4-(Cyclopropyl carbonyl)piperazin-1-yl]-2-fluoro-phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(4-Acetylpiperazin-1-yl)-2-fluorophenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

4-[3-Fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]-N,N-dimethylpiperazine-1-carboxamide;

1′-({1-[4-(4-Hydroxypiperidin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N,N-Dimethyl-1-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclo-propyl)phenyl]piperidine-4-carboxamide;

Methyl 4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]piperidine-1-carboxylate;

Ethyl 4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]piperidine-1-carboxylate;

1′-({1-[4-(1-Acetylpiperidin-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(1-Isobutyrylpiperidin-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(1-Propionylpiperidin-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[1-(3-Methylbutanoyl)piperidin-4-yl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

Methyl 4-hydroxy-4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclo-propyl)phenyl]piperidine-1-carboxylate;

Ethyl 4-hydroxy-4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclo-propyl)phenyl]piperidine-1-carboxylate;

Isopropyl 4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclo-propyl)phenyl]piperazine-1-carboxylate;

1′-[(1-{4-[6-(Pyrrolidin-1-ylcarbonyl)pyridin-3-yl]phenyl}cyclo-propyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N-Ethyl-N-methyl-5-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclo-propyl)phenyl]pyridine-2-carboxamide;

N,N-Diethyl-5-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclo-propyl)phenyl]pyridine-2-carboxamide;

tert-Butyl {4-[5-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclo-propyl)pyridin-2-yl]phenyl}carbamate; and

N,N-Dimethyl-1-[5-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclo-propyl)pyridin-2-yl]piperidine-4-carboxamide;

or pharmaceutically acceptable salt thereof.

21. A compound of claim 1 selected from:

1′-({1-[2-Fluoro-4-(2-oxopyrrolidin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(2-Oxoazetidin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[2-Fluoro-4-(2-oxoazetidin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

Propyl 4-[5-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)pyridin-2-yl]piperazine-1-carboxylate;

Isobutyl 4-[5-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)pyridin-2-yl]piperazine-1-carboxylate;

Isopropyl 4-[5-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)pyridin-2-yl]piperazine-1-carboxylate;

Ethyl 4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]piperazine-1-carboxylate;

Propyl 4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]piperazine-1-carboxylate;

Isobutyl 4-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]piperazine-1-carboxylate;

1′-[(1-{4-[4-(Cyclopropylacetyl)piperazin-1-yl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[4-(Cyclopropylacetyl)piperazin-1-yl]-2-fluorophenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[4-(3-Methylbutanoyl)piperazin-1-yl]phenyl}cyclopropyl)carbonyl]-3H-2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{2-Fluoro-4-[4-(3-methylbutanoyl)piperazin-1-yl]phenyl}cyclopropyl)carbonyl]-3H -spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[4-(Tetrahydro-2H-pyran-4-ylcarbonyl)piperazin-1-yl]phenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

Ethyl 4-[3-fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]piperazine-1-carboxylate;

Propyl 4-[3-fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]piperazine-1-carboxylate;

4-[3-Fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]-N-methylpiperazine-1-carboxamide;

1′-({1-[2-Fluoro-4-(4-isobutyrylpiperazin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-[(1-{4-[4-(Cyclopropylacetyl)piperazin-1-yl]-2-fluorophenyl}cyclopropyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N,N-Dimethyl-5-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]pyridine-2-carboxamide;

N-Ethyl-5-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]pyridine-2-carboxamide;

N-Isopropyl-5-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]pyridine-2-carboxamide;

5-[3-Fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]-N-methylpyridine-2-carboxamide;

5-[3-Fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]-N-ethylpyridine-2-carboxamide;

5-[3-Fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]-N-i-propylpyridine-2-carboxamide;

5-[3-Fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]-N,N-dimethylpyridine-2-carboxamide;

6-[3-Fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]-N-methylnicotinamide;

6-[3-Fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]-N,N-dimethylnicotinamide;

N-Methyl-6-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]nicotinamide;

N,N-Dimethyl-6-[4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]nicotinamide;

1′-({1-[4-(1-Isobutyryl-1,2,3,6-tetrahydropyridin-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[4-(1-Propionyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[6-(2-Oxoazetidin-1-yl)pyridin-3-yl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

Methyl [3-fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]carbamate;

1′-[(1-{4-[4-(Cyclopropylcarbonyl)piperazin-1-yl]phenyl}cyclobutyl)carbonyl]-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[2-Fluoro-4-(1H-1,2,3-triazol-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[2-Fluoro-4-(2H-1,2,3-triazol-2-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[2-Fluoro-4-(1H-1,2,4-triazol-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

1′-({1-[2-Fluoro-4-(4H-1,2,4-triazol-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one;

N-Ethyl-5-[3-fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]pyridine-2-carboxamide; and

5-[3-Fluoro-4-(1-{[3-oxo-1′H,3H-spiro[2-benzofuran-1,3′-pyrrolidin]-1′-yl]carbonyl}cyclopropyl)phenyl]-N-isopropylpyridine-2-carboxamide; or pharmaceutically acceptable salt thereof.

22. A method of treating a disease in a patient, wherein said disease is obesity, diabetes, glucose intolerance, insulin resistance, hyperglycemia, hyperlipidemia, glaucoma, hypertension, osteoporosis, inflammation, renal disease, atherosclerosis, arteriosclerosis, coronary artery disease, thrombosis, angina, peripheral vascular disease, vascular wall damage, stroke, dyslipidemia, hyperlipoproteinaemia, diabetic dyslipidemia, mixed dyslipedemia, hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, or general aldosterone-related target organ damage, comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or pharmaceutically acceptable salt thereof.

23. A composition comprising a compound of claim 1 , or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

24. A method for treating metabolic syndrome in a patient comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or pharmaceutically acceptable salt thereof.

25. A method for treating type 2 diabetes in a patient comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or pharmaceutically acceptable salt thereof.

Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE RECEIVING PARTY INFORMATION PREVIOUSLY RECORDED ON REEL 035920 FRAME 0576. ASSIGNOR(S) HEREBY CONFIRMS THE RECEIVING PARTY NAME SHOULD BE RECORDED AS TWO PARTIES. Recorded Jul 2, 2015
From: INCYTE CORPORATION
To: INCYTE HOLDINGS CORPORATION; INCYTE CORPORATION
Reel/Frame 036054/0740 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 16, 2015
From: INCYTE CORPORATION
To: INCYTE HOLDINGS CORPORATION AND INCYTE CORPORATION
Reel/Frame 035920/0576 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 30, 2005
From: YAO, WENQING; ZHUO, JINCONG; XU, MEIZHONG; METCALF, BRIAN W.; HE, CHUNHONG; QIAN, DING-QUAN; ZHANG, COLIN
To: INCYTE CORPORATION
Reel/Frame 016683/0729 →