Piperazine derivatives and methods of use

1. A compound of Formula I

wherein q is 1;

wherein t is 1;

wherein X is selected from NH;

wherein R is selected from:

a) 1,2,3,4-tetrahydronaphth-1-yl; or 1,2,3,4-tetrahydronaphth-2-yl which may be substituted with one to three basic moieties, and optionally substituted with one to three groups independently selected from halo, hydroxyl, cyano, oxo, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl

wherein R 1 is selected from H, C 1-4 -alkyl;

wherein R 2 is selected from aryl wherein R 2 is optionally substituted with one to five groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , or (C 1 -C 6 )alkyl;

wherein R 3 , R 3a , R 4 , R 4a , R 5 and R 5a are independently selected from H, C 1-3 alkyl and substituted C 1-3 alkyl;

or wherein R 3 and R 3a together form oxo, or R 4 and R 4a together form oxo, or R 5 and R 5a together form oxo;

wherein R 8 and R 8′ independently are H or selected from lower alkyl, aryl and heteroaryl, each of which is optionally substituted with one, two or three groups independently, selected from lower alkyl, halogen, lower alkoxy, hydroxy, amino, mono- or dialkylamino, and trifluoromethyl;

wherein R x is selected from H, (C 1 -C 3 )haloalkyl, and (C 1 -C 3 )alkyl; and

wherein each substituted alkyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl and substituted saturated or partially saturated heterocyclyl is substituted with one to three groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, (C 1 -C 6 )haloalkyl, oxo, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, di(C 1 -C 6 )alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , and —NR 8 C(O)R 8′ ,

or pharmaceutically acceptable salts thereto provided the basic substiuent is not 2-pyridyl, 3-pyridyl or 2-oxo-piperaziny-4-ylmethyl.

2. Compound of claim 1 wherein R is selected from 1,2,3,4-tetrahydronaphth-1-yl, or 1,2,3,4-tetrahydronaphth-2-yl substituted with one to two basic moieties, and optionally substituted with one to three groups independently selected from halo, hydroxyl, cyano, oxo, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl.

3. The compound of claim 2 wherein R is selected from 1,2,3,4-tetrahydronaphth-1-yl or 1,2,3,4-tetrahydronaphth-2-yl substituted with a basic moiety, optionally substituted with chloro.

4. Compound of claim 1 wherein R 1 is H or methyl.

5. Compound of claim 1 wherein R 2 is selected from naphthyl or phenyl wherein R 2 is optionally substituted with one to five groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , or (C 1 -C 6 )alkyl.

6. Compound of claim 1 wherein R 2 is selected from 2,4,6-trimethylphenyl, 3,4-dichlorophenyl, 3-chloro-4-methylphenyl, 4-chloro-3-methylphenyl, 4-methoxyphenyl, 4-methylphenyl, 4-chlorophenyl and 4-tert-butylphenyl.

7. Compound of claim 1 wherein the basic substituent on R is selected from amino, cycloalkylamino(C 1 -C 6 )alkyl, cycloalkyl(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, heterocyclylamino(C 1 -C 6 )alkyl, heterocyclyl(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, arylamino(C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, C 1-6 -alkylamino-C 1-6 -alkoxy, C 1-6 -alkylamino-C 1-6 -alkoxy-C 1-6 -alkoxy, amino(C 1 -C 6 )alkoxy, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, C 1-4 -alkylamino-C 2-6 -alkenyl, di-C 1-4-alkylamino-C 2-4-alkenyl, 5-8 membered nitrogen-containing heterocyclyl-C 2-6 -alkenyl, heterocyclyl-(C 1 -C 6 )alkylamino(C 2 -C 6 )alkyl, 5-6 membered heterocyclyloxy, 5-6 membered nitrogen-containing heterocyclyl and 5-7 membered nitrogen-containing heterocyclyl-alkyl; and wherein each of said basic substituents is optionally substituted with one to three groups independently selected from halo, —NH 2 , hydroxyl, cyano, —CF 3 , (C 1 -C 6 )alkylamino, oxo, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, di(C 1 -C 6 )alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl, wherein each substituted (C 1 -C 6 )alkyl, substituted aryl substituted heteroaryl and substituted saturated or partially saturated heterocyclyl is optionally substituted with one to three groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, (C 1 -C 6 )haloalkyl, oxo, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, di(C 1 -C 6 )alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , and —NR 8 C(O)R 8′ .

8. The compound of claim 7 wherein the basic substituent on R is selected from amino, mono-C 1-4 -alkylamino-C 1-4 alkyl, di-C 1-4 -alkylamino-C 1-4 -alkyl, mono-C 1-4 -alkylamino-C 2-4 -alkenyl, di-C 1-4 -alkylamino-C 2-4 -alkenyl, 5-8 membered nitrogen-containing heterocycyl-C 2-4 -alkenyl, optionally substituted 5-6 membered nitrogen-containing heterocyclyl and 5-8 membered nitrogen-containing heterocyclyl-C 1-4 -alkyl.

9. The compound of claim 8 wherein the basic substituent on R is selected from amino, aminomethyl, isopropylaminomethyl, t-butylaminomethyl, 2-t-butylaminomethyl, 2-tert-butylamino-1-methyl-ethyl, 1-tert-butylaminoethyl, 1-(tert-butylamino-methyl)-vinyl, 1-piperidin-1-ylmethyl)-vinyl, N-isobutyl-aminomethyl, N-isobutyl-aminoethyl, (2,2-dimethyl)propylaminomethyl, N-isopropyl-N-ethylaminomethyl, N-isopropyl-N-methylaminomethyl, N-t-butyl-N-methylaminomethyl, N-iso-butyl-N-methylaminomethyl, N-t-butyl-N-ethylaminomethyl, N-isobutyl-N-methylaminomethyl, N-t-butyl-N-isopropyl-aminomethyl, N,N-di(isopropyl)aminomethyl, N,N-dimethylaminomethyl, N,N-diethyl-aminomethyl, N,N-di(t-butyl)-aminomethyl, cyclopropylaminomethyl, cyclopropylaminomethyl, cyclopropylmethylaminomethyl, cyclopropylmethylaminomethyl, cyclobutylaminomethyl, cyclobutylaminoetyl, cyclobutylmethylaminomethyl, cyclobutylmethylaminoethyl, 4,5-dihydro-imidazolyl, 1-piperidinylmethyl, 4-fluoropiperidin-1-ylmethyl, 4,4-difluoropiperidin-1-ylmethyl, 3-hydroxypiperidin-1-ylmethyl, 4-hydroxypiperidin-1-methyl, 4-(piperidin-1-yl)piperidinylmethyl, 4-(dimethylamino)-piperidin-1-ylmethyl, 2,6-dimethylpiperidin-1-ylmethyl, 4-morpholinylmethyl, 1-pyrrolidinylmethyl, 2-methylpyrrolidin-1-methyl, 2,5-dimethylpyrrolidin-1-ylmethyl, piperazin-1-ylmethyl, azocan-1-ylmethyl, azepan-1-ylmethyl, (7-azabicyclo[2.2.1]hept-7-yl)methyl, (1,3,3-trimethyl-6-azaicyclo[3.2.1]oct-6-yl)methyl, 2-piperidinyl and 4-methylpiperazin-1-ylmethyl.

10. The compound of claim 1 wherein R 3 and R 3a together form oxo; wherein R 4 and R 4a are independently selected from H and C 1-3 alkyl; and wherein R 5 and R 5a are independently H.

11. The compound of claim 10 wherein R 3 and R 3a together form oxo; wherein R 4 and R 4a are independently selected from H and methyl; and wherein R 2 and R 5a are independently H.

12. The compound of claim 1 wherein R 8 and R 8′ independently are H or selected from lower alkyl, aryl and heteroaryl, each of which is optionally substituted with one, two or three groups independently selected from lower alkyl, halogen, lower alkoxy, hydroxy, amino, mono-alkylamino, dialkylamino, and trifluoromethyl.

13. Compound of claim 1 wherein R x is H, methyl or trifluoromethyl.

14. Compound of claim 1 wherein R x is H.

15. A compound of Formula III:

wherein R is selected from 1,2,3,4-tetrahydronaphth-1-yl or 1,2,3,4-tetrahydronaphth-2-yl substituted with one to two basic moieties, and optionally substituted with one to three groups independently selected from halo, hydroxyl, cyano, oxo, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , (C 1 -C 6 alkyl, substituted (C 1 -C 6 )alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; wherein each substituted (C 1 -C 6 )alkyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl and substituted saturated or partially saturated heterocyclyl is substituted with one to three groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, (C 1 -C 6 )haloalkyl, oxo, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, di(C 1 -C 6 )alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , and —NR 8 C(O)R 8′ ;

wherein R 1 is selected from H, and C 1-2 -alkyl;

wherein R 2 is selected from aryl wherein R 2 is optionally substituted with one to five groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , or (C 1 -C 6 )alkyl; and

wherein R 8 and R 8′ independently are H or selected from lower alkyl, aryl and heteroaryl, each of which is optionally substituted with one, two or three groups independently selected from lower alkyl, halogen, lower alkoxy, hydroxy, amino, mono- or dialkylamino, and trifluoromethyl; or pharmaceutically acceptable salts thereof; provided the basic substiuent is not 2-pyridyl, 3-pyridyl or 2-oxo-piperaziny-4-ylmethyl.

16. The compound of claim 15 wherein R is selected from 1,2,3,4-tetrahydronaphth-1-yl or 1,2,3,4-tetrahydronaphth-2-yl substituted with a basic moiety, optionally substituted with chloro.

17. The compound of claim 15 wherein each R 2 is selected from naphthyl or phenyl wherein R 2 is optionally substituted with one to five groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , or (C 1 -C 6 )alkyl;

wherein R 1 is selected from H and C 1-2 -alkyl;

wherein the basic substituent on R is selected from amino, cycloalkylamino(C 1 -C 6 )alkyl, cycloalkyl(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, heterocyclylamino(C 1 -C 6 )alkyl, heterocyclyl(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, arylamino(C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, C 1-6 -alkylamino-C 1-6 -alkoxy, C 1-6 -alkylamino-C 1-6 -alkoxy-C 1-6 -alkoxy, amino(C 1 -C 6 )alkoxy, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, C 1-4 -alkylamino-C 2-6 -alkenyl, di-C 1-4 -alkylamino-C 2-4 -alkenyl, 5-8 membered nitrogen-containing heterocyclyl-C 2-6 -alkenyl, heterocyclyl-(C 1 -C 6 )alkylamino(C 2 -C 6 )alkyl, 5-6 membered heterocyclyloxy, 5-6 membered nitrogen-containing heterocyclyl and 5-8 membered nitrogen-containing heterocyclyl-alkyl; and wherein each of said basic substituents is optionally substituted with one to three groups independently selected from halo, —NH 2 , hydroxyl, cyano, —CF 2 , (C 1 -C 6 )alkylamino, oxo, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, di(C 1 -C 6 )alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl, wherein each substituted (C 1 -C 6 )alkyl, substituted aryl substituted heteroaryl and substituted saturated or partially saturated heterocyclyl is optionally substituted with one to three groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 4 )alkylamino, (C 1 -C 4 )haloalkyl, oxo, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkoxy(C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkynyl, di(C 1 -C 4 )alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , and —NR 8 C(O)R 8′ .

18. The compound of claim 17 wherein R 2 is selected from 2-naphthyl or phenyl wherein each R 2 is optionally substituted;

wherein R 1 is H; and

wherein the basic substituent on R is selected from amino, mono-C 1-4 -alkylamino-C 1-4 -alkyl, di-C 1-4 -alkylamino-C 1-4 -alkyl, mono-C 1-4 -alkylamino-(C 2 -C 4 )-alkenyl, di-C 1-4 -alkylamino-(C 2 -C 4 )-alkenyl, 5-8 membered nitrogen-containing heterocyclyl-(C 2 -C 4 )-alkenyl, optionally substituted 5-6 membered nitrogen-containing heterocyclyl and 5-8 membered nitrogen-containing heterocyclyl-C 1-4 -alkyl.

19. The compound of claim 15 wherein R 1 is H.

20. The compound of claim 15 wherein the basic substituent on R is selected from amino, aminomethyl, isopropylaminomethyl, t-butylaminomethyl, 2-t-butylaminomethyl, 2-tert-butylamino-1-methyl-ethyl, 1-tert-butylaminomethyl, 1-(tert-butylamino-methyl)-vinyl, 1-(piperidin-1-ylmethyl)-vinyl, N-isobutyl-aminomethyl, N-isobutyl-aminoethyl, (2,2-dimethyl)propylaminomethyl, N-isopropyl-N-ethylaminomethyl, N-isopropyl-N-methylaminomethyl, N-t-butyl-N-methylaminomethyl, N-iso-butyl-N-methyl-aminomethyl, N-t-butyl-N-ethylaminomethyl, N-isobutyl-N-methylaminomethyl, N-t-butyl-N-isopropylaminomethyl, N,N-di(isopropyl)aminomethyl, N,N-dimethylaminomethyl, N,N-diethylaminomethyl, N,N-di(t-butyl)-aminomethyl, cyclopropylaminomethyl, cyclopropylaminoethyl, cyclopropylmethylaminomethyl, cyclopropylmethylaminoethyl, cyclobutylaminomethyl, cyclobutylaminoethyl, cyclobutylmethylaminomethyl, cyclobutylmethylaminoethyl, 4,5-dihydro-imidazolyl, 1-piperidinylmethyl, 4-fluoropiperidin-1-ylmethyl, 4,4-difluoropiperidin-1-ylmethyl, 3-hydroxypiperidin-1-ylmethyl, 4-hydroxy-piperidin-1-ylmethyl, 4-(piperidin-1-yl)piperidinylmethyl, 4-(dimethylamino)piperidin-1-ylmethyl, 2,6-dimethylpiperidin-1-ylmethyl, 4-morpholinylmethyl, 1-pyrrolidinylmethyl, 2-methylpyrrolidin-1-ylmethyl, 2,5-dimethylpyrrolidin-1-ylmethyl, piperazin-1-ylmethyl, azocan-1-ylmethyl, azepan-1-ylmethyl, (7-azabicyclo[2.2.1]hept-7-yl)methyl, (1,3,3-trimethyl-6-azaicyclo[3.2.1]oct-6-yl)methyl, 2-piperidinyl and 4-methylpiperazin-1-ylmethyl.

21. The compound of claim 15 or pharmaceutically acceptable salts thereof selected from:

2-[3-Oxo-1-(2,4,6-trimethylbenzenesulfonyl)-piperizin-2(R,S)-yl]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-acetamide;

N-((1R)-6-(((1,1-Dimethylethyl)amino)methyl}-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide; and

2-[3-Oxo-1-(toluene-4-sulfonyl)piperizin-2-yl]-N-(6-piperidin-1-ylmethyl-1,2,3,4-tetrahydronaphthalen-1-yl)-acetamide.

22. A compound of Formula IV

wherein the C ring is a 6 membered saturated carbocyclic moiety; optionally substituted with halo, hydroxyl, cyano, oxo, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —(C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl;

wherein R 1 is selected from

wherein R 1 is independently selected from H and C 1-2 alkyl;

wherein R 2 is selected from aryl wherein R 2 is optionally substituted with one to five groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , or (C 1 -C 6 )alkyl;

wherein R 8 and R 8′ independently are H or selected from lower alkyl, aryl and heteroaryl, each of which is optionally substituted with one, two or three groups independently selected from lower alkyl, halogen, lower alkoxy, hydroxy, amino, mono- or dialkylamino, and trifluoromethyl; and

wherein R 9 , R 10 and R 11 are the same or different and represent H, halo, —NH 2 , hydroxyl, cyano, —CF 3 , (C 1 -C 6 )alkylamino, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, di(C 1 -C 6 )alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , a basic moiety, (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; wherein each substituted (C 1 -C 6 )alkyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl and substituted saturated or partially saturated heterocyclyl is substituted with one to three groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, (C 1 -C 6 )haloalkyl, oxo, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, di(C 1 -C 6 )alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , and —NR 8 C(O)R 8′ ;

and pharmaceutically acceptable salts thereof provided at least one of R 9 , R 10 and R 11 is a basic moiety; further provided the basic substiuent is not 2-pyridyl, 3-pyridyl or 2-oxo-piperaziny-4-ylmethyl.

23. The compound of claim 22 wherein R 9 and R 11 are H; and

wherein R 10 is selected from amino, aminomethyl, isopropylaminomethyl, t-butylaminomethyl, 2-t-butylaminomethyl, 2-tert-butylamino-1-methyl-ethyl, 1-tert-butylaminomethyl, 1-(tert-butylamino-methyl)-vinyl, 1-(piperidin-1-ylmethyl)-vinyl, N-isobutyl-aminomethyl, N-isobutyl-aminoethyl, (2,2-dimethyl)propylaminomethyl, N-isopropyl-N-ethylaminomethyl, N-isopropyl-N-methylaminomethyl, N-t-butyl-N-methylaminomethyl, N-iso-butyl-N-methylaminomethyl, N-t-butyl-N-ethylaminomethyl, N-isobutyl-N-methylaminomethyl, N-t-butyl-N-isopropylaminomethyl, N,N-di(isopropyl)aminomethyl, N,N-dimethylaminomethyl, N,N-diethylaminomethyl, N,N-di(t-butyl)-aminomethyl, cyclopropylaminomethyl, cyclopropylaminoethyl, cyclopropylmethylaminomethyl, cyclopropylmethylaminoethyl, cyclobutylaminomethyl, cyclobutylaminoethyl, cyclobutylmethylaminomethyl, cyclobutylmethylaminoethyl, 4,5-dihydro-imidazolyl, 1-piperidinylmethyl, 4-fluoropiperidin-1-ylmethyl, 4,4-difluoropiperidin-1-ylmethyl, 3-hydroxypiperidin-1-ylmethyl, 4-hydroxypiperidin-1-ylmethyl, 4-(piperidin-1-yl)-piperidinylmethyl, 4-(dimethylamino)piperidin-1-ylmethyl, 2,6-dimethylpiperidin-1-ylmethyl, 4-morpholinylmethyl, 1-pyrrolidinylmethyl, 2-methylpyrrolidin-1-ylmethyl, 2,5-dimethyl-pyrrolidin-1-ylmethyl, piperazin-1-ylmethyl, azocan-1-ylmethyl, azepan-1-ylmethyl, (7-azabicyclo[2.2.1]hept-7-yl)methyl, (1,3,3-trimethyl-6-azaicyclo[3.2.1]oct-6yl)methyl, 2-piperidinyl and 4-methylpiperazin-1-ylmethyl.

24. The compound of claim 22 wherein R 10 and R 11 are H; and

wherein R 9 is selected from amino, aminomethyl, isopropylaminomethyl, t-butylaminomethyl, 2-t-butylaminomethyl, 2-tert-butylamino-1-methyl-ethyl, 1-tert-butylaminomethyl, 1-(tert-butylamino-methyl)-vinyl, 1-(piperidin-1-ylmethyl)-vinyl, N-isobutyl-aminomethyl, N-isobutyl-aminoethyl, (2,2-dimethyl)propylaminomethyl, N-isopropyl-N-ethylaminomethyl, N-isopropyl-N-methylaminomethyl, N-t-butyl-N-methylaminomethyl, N-iso-butyl-N-methylaminomethyl, N-t-butyl-N-ethylaminomethyl, N-isobutyl-N-methylaminomethyl, N-t-butyl-N-isopropylaminomethyl, N,N-di(isopropyl)aminomethyl, N,N-dimethylaminomethyl, N,N-diethylaminomethyl, N,N-di(t-butyl)-aminomethyl, cyclopropylaminomethyl, cyclopropylaminoethyl, cyclopropylmethylaminomethyl, cyclopropylmethylaminoethyl, cyclobutylaminomethyl, cyclobutylaminoethyl, cyclobutylmethylaminomethyl, cyclobutylmethylaminoethyl, 4,5-dihydro-imidazolyl, 1-piperidinylmethyl, 4-fluoropiperidin-1-ylmethyl, 4,4-difluoropiperidin-1-ylmethyl, 3-hydroxypiperidin-1-ylmethyl, 4-hydroxypiperidin-1-ylmethyl, 4-(piperidin-1-yl)-piperidinyl-methyl, 4-(dimethylamino)piperidin-1-ylmethyl, 2,6-dimethylpiperidin-1-ylmethyl, 4-morpholinylmethyl, 1-pyrrolidinylmethyl, 2-methylpyrrolidin-1-ylmethyl, 2,5-dimethyl-pyrrolidin-1-ylmethyl, piperazin-1-ylmethyl, azocan-1-ylmethyl, azepan-1-ylmethyl, (7-azabicyclo[2.2.1]hept-7-yl)methyl, (1,3,3-trimethyl-6-azaicyclo[3.2.1]oct-6yl)methyl, 2-piperidinyl and 4-methylpiperazin-1-ylmethyl.

25. The compound of claim 22 wherein R 9 and R 10 are H; and

wherein R 11 is selected from amino, aminomethyl, isopropylaminomethyl, t-butylaminomethyl, 2-t-butylaminomethyl, 2-tert-butylamino-1-methyl-ethyl, 1-tert-butylaminomethyl, 1-(tert-butylamino-methyl)-vinyl, 1-(piperidin-1-ylmethyl)-vinyl, N-isobutyl-aminomethyl, N-isobutyl-aminoethyl, (2,2-dimethyl)propylaminomethyl, N-isopropyl-N-ethylaminomethyl, N-isopropyl-N-methylaminomethyl, N-t-butyl-N-methylaminomethyl, N-iso-butyl-N-methylaminomethyl, N-t-butyl-N-ethylaminomethyl, N-isobutyl-N-methylaminomethyl, N-t-butyl-N-isopropylaminomethyl, N,N-di(isopropyl)aminomethyl, N,N-dimethylaminomethyl, N,N-diethylaminomethyl, N,N-di(t-butyl)-aminomethyl, cyclopropylaminomethyl, cyclopropylaminoethyl, cyclopropylmethylaminomethyl, cyclopropylmethylaminoethyl, cyclobutylaminomethyl, cyclobutylaminoethyl, cyclobutylmethylaminomethyl, cyclobutylmethylaminoethyl, 4,5-dihydro-imidazolyl, 1-piperidinylmethyl, 4-fluoropiperidin-1-ylmethyl, 4,4-difluoropiperidin-1-ylmethyl, 3-hydroxypiperidin-1-ylmethyl, 4-hydroxypiperidin-1-ylmethyl, 4-(piperidin-1-yl)-piperidinyl-methyl, 4-(dimethylamino)piperidin-1-ylmethyl, 2,6-dimethylpiperidin-1-ylmethyl, 4-morpholinylmethyl, 1-pyrrolidinylmethyl, 2-methylpyrrolidin-1-ylmethyl, 2,5-dimethyl-pyrrolidin-1-ylmethyl, piperazin-1-ylmethyl, azocan-1-ylmethyl, azepan-1-ylmethyl, (7-azabicyclo[2.2.1]hept-7-yl)methyl, (1,3,3-trimethyl-6-azaicyclo[3.2.1]oct-6yl)methyl, 2-piperidinyl and 4-methylpiperazin-1-ylmethyl.

26. The compound of claim 22 wherein R 2 is selected from 2-naphthyl or phenyl wherein each R 2 is optionally substituted with one to five groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkyl-amino, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , or (C 1 -C 6 )alkyl.

27. The compound of claim 22 wherein R 2 is selected from 2-naphthyl, 1-naphthyl, phenyl, 3-chlorophenyl, 4-chlorophenyl, 3,5-dichlorophenyl, 3,4-dichlorophenyl, 2,4,6-trichlorophenyl, 3-fluorophenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-biphenyl, 3-chloro-4-methylphenyl, 4-chloro-3-methylphenyl, and 3-methylphenyl.

28. The compound of claim 22 wherein R 1 is H or methyl.

29. The compound of claim 22 wherein R 2 is 2-naphthyl.

30. The compound of claim 22 wherein R 2 is 3,4-dichlorophenyl.

31. A compound of Formula VI:

wherein R is selected from 1,2,3,4-tetrahydronaphth-1-yl or 1,2,3,4-tetrahydronaphth-2-yl substituted with one to two basic moieties, and optionally substituted with one to three groups independently selected from halo, hydroxyl, cyano, oxo, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl; wherein each substituted, (C 1 -C 6 )alkyl, substituted aryl, substituted heteroaryl, substituted cycloalkyl and substituted saturated or partially saturated heterocyclyl is substituted with one to three groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, (C 1 -C 6 )haloalkyl, oxo, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, di(C 1 -C 6 )alkylamino, —C(O) 8 , —COOR 8 , —C(O)NR 8 R 8′ , and —NR 8 C(O)R 8′ ;

wherein R 1 is selected from H, and C 1-2 -alkyl;

wherein R 2 is aryl wherein R 2 is optionally substituted with one to five groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, oxo, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , or (C 1 -C 6 )alkyl; and

wherein R 8 and R 8′ independently are H or selected from lower alkyl, aryl and heteroaryl, each of which is optionally substituted with one, two or three groups independently selected from lower alkyl, halogen, lower alkoxy, hydroxy, amino, mono- or dialkylamino, and trifluoromethyl;

and pharmaceutically acceptable salts thereof; provided the basic substiuent is not 2-pyridyl, 3-pyridyl or 2-oxo-piperaziny-4-ylmethyl.

32. The compound of claim 31 wherein R is selected from 1,2,3,4-tetrahydronaphth-1-yl or 1,2,3,4-tetrahydronaphth-2-yl substituted with a basic moiety, optionally substituted with chloro.

33. The compound of claim 31 wherein R 2 is naphthyl, or phenyl wherein R 2 is optionally substituted with one to five groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 6 )alkylamino, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , or (C 1 -C 6 )alkyl

wherein R 1 is selected from H and C 1-2 -alkyl;

wherein the basic substituent on R is selected from amino, cycloalkylamino(C 1 -C 6 )alkyl, cycloalkyl(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, heterocyclylamino(C 1 -C 6 )alkyl, heterocyclyl(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, arylamino(C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, C 1-6 -alkylamino-C 1-6 -alkoxy, C 1-6 -alkylamino-C 1-6 -alkoxy-C 1-6 -alkoxy, amino(C 1 -C 6 )alkoxy, amino(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamino(C 1 -C 6 )alkyl, C 1-4 -alkylamino-C 2-6 -alkenyl, di-C 1-4-alkylamino-C _hd 2 - 4 -alkenyl, 5-8 membered nitrogen-containing heterocyclyl-C 2-6 -alkenyl, heterocyclyl-(C 1 -C 6 )alkylamino(C 2 -C 6 )alkyl, 5-6 membered heterocyclyloxy, 5-6 membered nitrogen-containing heterocyclyl and 5-7 membered nitrogen-containing heterocyclyl-alkyl; and wherein each of said basic substituents is optionally substituted with one to three groups independently selected from halo, —NH 2 , hydroxyl, cyano, —CF 3 , (C 1 -C 6 )alkylamino, oxo, (C 1 -C 6 )alkoxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, di(C 1 -C 6 )alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , —NR 8 C(O)R 8′ , (C 1 -C 6 )alkyl, substituted (C 1 -C 6 )alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl, wherein each substituted (C 1 -C 6 )alkyl, substituted aryl substituted heteroaryl and substituted saturated or partially saturated heterocyclyl is optionally substituted with one to three groups independently selected from halo, —NH 2 , hydroxyl, cyano, (C 1 -C 4 )alkylamino, (C 1 -C 4 )haloalkyl, oxo, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkoxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkynyl, di(C 1 -C 4 )alkylamino, —C(O)R 8 , —COOR 8 , —C(O)NR 8 R 8′ , and —NR 8 C(O)R 8′ .

34. The compound of claim 33 wherein R 2 is 2-naphthyl or phenyl wherein each R 2 is optionally substituted;

wherein R 1 is H; and

wherein the basic substituent on R is selected from amino, mono-CC 1-4 -alkylamino-C 1-4 -alkyl, di-C 1-4 -alkylamino-C 1-4 -alkyl, mono-C 1-4 -alkylamino-C 2-4 -alkenyl, di-C 1-4 -alkylamino-C 2-4 -alkenyl, 5-8 membered nitrogen-containing heterocyclyl-C 2-4 -alkenyl, optionally substituted 5-6 membered nitrogen-containing heterocyclyl and 5-8 membered nitrogen-containing heterocyclyl-C 1-4 -alkyl;

and pharmaceutically acceptable derivatives thereof.

35. The compound of claim 31 wherein R 1 is H.

36. The compound of claim 31 wherein the basic substituent on R is selected from amino, aminomethyl, isopropylaminomethyl, t-butylaminomethyl, 2-t-butylaminomethyl, 2-tert-butylamino-1-methyl-ethyl, 1-tert-butylaminomethyl, 1-(tert-butylamino-methyl)-vinyl, 1-(piperidin-1-ylmethyl)-vinyl, N-isobutyl-aminomethyl, N-isobutyl-aminoethyl, (2,2-dimethyl)propylaminomethyl, N-isopropyl-N-ethylaminomethyl, N-isopropyl-N-methylaminomethyl, N-t-butyl-N-methylaminomethyl, N-iso-butyl-N-methylaminomethyl, N-t-butyl-N-ethylaminomethyl, N-isobutyl-N-methylaminomethyl, N-t-butyl-N-isopropylaminomethyl, N,N-di(isopropyl)aminomethyl, N,N-dimethylaminomethyl, N,N-diethylaminomethyl, N,N-di(t-butyl)-aminomethyl, cyclopropylaminomethyl, cyclopropylaminoethyl, cyclopropylmethylaminomethyl, cyclopropylmethylaminoethyl, cyclobutylaminomethyl, cyclobutylaminoethyl, cyclobutylmethylaminomethyl, cyclobutylmethylaminoethyl, 4,5-dihydro-imidazolyl, 1-piperidinylmethyl, 4-fluoropiperidin-1-ylmethyl, 4,4-difluoropiperidin-1-ylmethyl, 3-hydroxypiperidin-1-ylmethyl, 4-hydroxypiperidin-1-ylmethyl, 4-(piperidin-1-yl)-piperidinylmethyl, 4-(dimethylamino)piperidin-1-methyl, 2,6-dimethylpiperidin-1-ylmethyl, 4-morpholinylmethyl, 1-pyrrolidinylmethyl, 2-methylpyrrolidin-1-ylmethyl, 2,5-dimethyl-pyrrolidin-1-ylmethyl, piperazin-1-ylmethyl, azocan-1-ylmethyl, azepan-1-ylmethyl, (7-azabicyclo[2.2.1]hept-7-yl)methyl, (1,3,3-trimethyl-6-azaicyclo[3.2.1]oct-6yl)methyl, 2-piperidinyl and 4-methylpiperazin-1-ylmethyl.

37. The compound of claim 31 or pharmaceutically acceptable salts thereof selected from:

2-((2R,S)-5,5-dimethyl-3-oxo-1-((2,4,6-trimethylphenyl)sulfonyl)-2-piperazinyl)-N-(1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

N-[6-(tert-Butylamino-methyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-2-[5,5-dimethyl-3-oxo-1-(2,4,6-trimethyl-benzenesulfonyl)-piperazin-2(R,S)-yl]-acetamide

N-((1R,S)-6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-5,5-dimethyl -1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide; and

2-[5,5-Dimethyl-3-oxo-1-(toluene-4-sulfonyl)-piperizin-2(R,S)-yl]-N-(6-piperidin-1-ylmethyl-1,2,3,4-tetrahydronaphthalen-1(R)-yl)-acetamide.

38. The compound of claim 1 or pharmaceutically acceptable salts thereof selected from:

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((1R,S)-1-((2-methylpropyl)amino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1,2,3,6-tetrahydro-4-pyridinyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-(2-methylpropyl)-1,2,3,6-tetrahydro-4-pyridinyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-propyl-1,2,3,6-tetrahydro-4-pyridinyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((1R,S)-1-((2-methylpropyl)amino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-(phenylmethyl)-1,2,3,6-tetrahydro-4-pyridinyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-5-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-5-oxo-2-piperazinyl)-N-((1R)-6-(1-(1-piperidinylmethyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(3-pyridinyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-(1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(3-((2-methylpropyl)amino)-1-propynyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(3-((2-methylpropyl)amino)propyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(3-piperidinyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-pyridinyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-piperidinyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(3-((2-methylpropyl)amino)propyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-(1-piperidinylmethyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((1S)-1-methyl-2-(1-piperidinyl)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-(((2-methylpropyl)amino)methyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-(1-pyrrolidinylmethyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

3-((5R)-5-((((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetyl)amino)-5,6,7,8-tetrahydro-2-naphthalenyl)benzamide;

methyl 3-((5R)-5-((((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetyl)amino)-5,6,7,8-tetrahydro-2-naphthalenyl)benzoate;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(3-(methylsulfonyl)phenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

3-((5R)-5-((((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetyl)amino)-5,6,7,8-tetrahydro-2-naphthalenyl)benzoic acid;

2-fluoro-4-((5R)-5-((((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetyl)amino)-5,6,7,8-tetrahydro-2-naphthalenyl)benzoic acid;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(3-(((2-methylpropyl)amino)methyl)phenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-(1-piperidinylmethyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-(1-pyrrolidinylmethyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((4-methyl-1-piperazinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((3-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((2-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((3-chloro-4-fluorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chloro-2-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((2-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-3-oxo-1-(phenylsulfonyl)-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2,2-dimethylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2-methylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((cyclobutylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2-(1-pyrrolidinyl)ethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S) 1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(4-morpholinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((phenylmethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-(1-piperidinyl)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

methyl (2E)-3-((5R)-5-((((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetyl)amino)-5,6,7,8-tetrahydro-2-naphthalenyl)-2-propenoate;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(4-morpholinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((4-methyl-1-piperazinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2,2-dimethylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2-methylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((phenylmethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2-phenylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2-(2-fluorophenyl)ethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((cyclobutylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2-(1-pyrrolidinyl)ethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((3-methylbutyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((4-fluoro-1-piperidinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((1-naphthalenylmethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2-(2-(methyloxy)phenyl)ethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-(1-piperidinyl)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-((2-methylpropyl)amino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-((1,1-dimethylethyl)amino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-((2,2-dimethylpropyl)amino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-(cyclobutylamino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-((phenylmethyl)amino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-(4-morpholinyl)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-(1-pyrrolidinyl)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((2R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-2-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((2R)-6-(2-((2-(1-pyrrolidinyl)ethyl)amino)ethyl)-1,2,3,4-tetrahydro-2-naphthalenyl)acetamide;

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2-methylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((((1 S)-1-methylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2-(1-pyrrolidinyl)ethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-(1-piperidinyl)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-chlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(2-(1-piperidinyl)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(4-morpholinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

N-((1R)-6-((1R,S)-1-(cyclopentylamino)ethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((2,2-dimethylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-((4-fluoro-1-piperidinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(3-cyanophenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(3-(bis(2-methylpropyl)amino)propyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(3-((cyclopentylmethyl)amino)propyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(3-aminopropyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(3-aminopropyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(3-(bis(2-methylpropyl)amino)propyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-3-oxo-1-((4-((trifluoromethyl)oxy)phenyl)sulfonyl)-2-piperazinyl)acetamide;

N-((1R)-6-(((2-methylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-3-oxo-1-((4-((trifluoromethyl)oxy)phenyl)sulfonyl)-2-piperazinyl)acetamide;

N-((1R)-6-(((cyclopropylmethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-3-oxo-1-((4-((trifluoromethyl)oxy)phenyl)sulfonyl)-2-piperazinyl)acetamide;

N-((1R)-6-(((1-methylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-3-oxo-1-((4-((trifluoromethyl)oxy)phenyl)sulfonyl)-2-piperazinyl)acetamide;

N-((1R)-6-((cyclobutylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-3-oxo-1-((4-((trifluoromethyl)oxy)phenyl)sulfonyl)-2-piperazinyl)acetamide;

N-((1R)-6-(1-(((1,1-dimethylethyl)amino)methyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(1-(((cyclopropylmethyl)amino)methyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(1-((cyclobutylamino)methyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(1-(1-azetidinylmethyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(1-((4-fluoro-1-piperidinyl)methyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(3-(acetylamino)phenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(3-(hydroxymethyl)phenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(3-((cyclobutylamino)methyl)phenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(3-((cyclopentylamino)methyl)phenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(1-(((2,2-dimethylpropyl)amino)methyl)ethenyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-((4-fluoro-1-piperidinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((3-methylbutyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((3,3-dimethylbutyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((cyclohexylmethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((2-(2-fluorophenyl)ethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((2,2-dimethylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-((cyclopentylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((3-methylbutyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((cyclohexylmethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-((cyclohexylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((cyclopropylmethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-((cyclopentylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-((cyclopropylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(1-azepanylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((3R,S)-3-hydroxy-1-piperidinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((2-(methyloxy)ethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

N-((1R)-6-(((2-hydroxyethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide;

2-((2R,S)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((cyclopentylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((4-methyl-1-piperazinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((tetrahydro-2H-pyran4-ylamino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((cyclopropylmethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(3-((4-pyridinylmethyl)amino)propyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(3-((tetrahydro-2H-pyran-4-ylmethyl)amino)propyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((4-chloro-2,5-dimethylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((3,4-dichlorophenyl)sulfonyl)-5,5-dimethyl-3-oxo-2-piperazinyl)-N-((1R)-6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

1,1-dimethylethyl 4-((5R)-5-((((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetyl)amino)-5,6,7,8-tetrahydro-2-naphthalenyl)-3,6-dihydro-1(2H)-pyridinecarboxylate;

2-((2R,S)-1-((4-(1,1-dimethylethyl)phenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((2,5-dichlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((3,4-dichlorophenyl)sulfonyl)-5-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-((4-fluoro-1-piperidinyl)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-pyrrolidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1-((3,4-dichlorophenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2-methylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R,S)-1R-((3,5-dibromo-4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2R)-1-((3,5-dibromo-4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((2,2-dimethylpropyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

2-((2S)-1-((3,5-dibromo-4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(((1,1-dimethylethyl)amino)methyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide;

N-((1R)-6-(1-(cyclopropylmethyl)-1,2,3,6-tetrahydro-4-pyridinyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide; and

N-((1R)-6-(1-(cyclohexylmethyl)-1,2,3,6-tetrahydro-4-pyridinyl)-1,2,3,4-tetrahydro-1-naphthalenyl)-2-((2R,S)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)acetamide.

39. A compound selected from the group consisting of:

2-((R)-3-oxo-1-tosylpiperazin-2-yl)-N-((R)-6-(3-(piperidin1-yl)prop-1-en-2-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide;

N-((R)-6-((4-fluoropiperidin-1-yl)methyl)-1,2,3,4-tetrahydronaphthalen-1-yl)-2-((R)-3-oxo-1-tosylpiperazin-2-yl)acetamide;

N-((R)-6-((neopentylamino)methyl)-1,2,3,4-tetrahydronaphthalen-1-yl)-2-((R)-3-oxo-1-tosylpiperazin-2-yl)acetamide;

N-((R)-6-(azepan-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl)-2-((R)-3-oxo-1-(phenylsulfonyl)piperazin-2-yl)acetamide;

2-((R)-1-(4-chlorophenylsulfonyl)3-oxopiperazin-2-N-(R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide; and

N-methyl-2-((R)-3-oxo-1-tosylpiperazin-2-yl)-N-((R)-6-(piperidin-1-ylmethyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide; or

a pharmaceutically acceptable salt thereof.

40. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 1 .

41. A pharmaceutical composition for the treatment of disease conditions mediated by bradykinin consisting of pain and inflammation, in a mammalian subject, which comprises a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.

42. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound according to claim 39 .