Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV)

1. A compound of formula (I)

or a pharmaceutically acceptable salt, prodrug, salt of a prodrug, or a combination thereof, wherein

R 1 is selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl, heteroaryl, heterocycle, cycloalkyl and cycloalkenyl; and R 2 is —C(O)G;

G is R 4 ;

R 4 at each occurrence is independently selected from the group consisting of aryl, heteroaryl, cycloalkyl, cycloalkenyl, and heterocycle; wherein

the aryl, heteroaryl, heterocycle, cycloalkyl, cycloalkenyl, and the heterocycle moiety of heterocyclealkyl, represented by R 1 , and R 4 , are each independently unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of R 7 , alkyl, alkenyl, —CN, —NO 2 , halo, ethylenedioxy, methylenedioxy, oxo, —OR 7A , —OC(O)R 7A , —OC(O)OR 7A , —OS(O) 2 R 7A , —S(alkyl), —S(O)alkyl, —S(O) 2 R 7A , —S(O) 2 OR 7A , —S(O) 2 NR 7A R b , —C(O)R 7A , —C(O)OR 7A , —C(O)NR 7A R b , —NR 7A R b , —NOR 7A , —N(R b )C(O)R 7A , —N(R b )C(O)OR 7A , —N(R b )S(O) 2 R 7A , —N(R b )C(O)NR 7A R b , —N(R b )S(O) 2 NR 7A R b , haloalkyl, cyanoalkyl, nitroalkyl, -alkylenyl-OR 7A , -alkylenyl-OC(O)R 7A , -alkylenyl-OC(O)OR 7A , -alkylenyl-OS(O) 2 R 7A , -alkylenyl-S(alkyl), -alkylenyl-S(O)alkyl, -alkylenyl-S(O) 2 R 7A , -alkylenyl-S(O) 2 OR 7A , -alkylenyl-S(O) 2 NR 7A R b , -alkylenyl-C(O)R 7A , -alkylenyl-C(O)OR 7A , -alkylenyl-C(O)NR 7A R b , -alkylenyl-NR 7A R b , -alkylenyl-NOR 7A , -alkylenyl-N(R b )C(O)R 7A , -alkylenyl-N(R b )C(O)OR 7A , -alkylenyl-N(R b )S(O) 2 R 7A , -alkylenyl-N(R b )C(O)NR 7A R b , -alkylenyl-N(R b )S(O) 2 NR 7A R b and -alkylenyl-R 7 ;

R 7A at each occurrence is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, —R 7 and -alkylenyl-R 7 ; and

R 7 at each occurrence is independently selected from the group consisting of aryl, heteroaryl, cycloalkyl, cycloalkenyl and heterocycle;

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

is double bond;

m is 4;

Ar 1 is a phenyl group;

the phenyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, and heterocycle represented by Ar 1 and R 7 , are independently unsubstituted or substituted with 1, 2, 3, 4 and 5 substituents independently selected from the group consisting of alkyl, alkenyl, —CN, —NO 2 , halo, ethylenedioxy, methylenedioxy, oxo, —OR a , —OC(O)alkyl, —OC(O)Oalkyl, —OS(O) 2 alkyl, —S(alkyl), —S(O)alkyl, —S(O) 2 alkyl, —S(O) 2 OR a , —S(O) 2 NR a R b , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —NR a R b , —NOR a , —N(R b )C(O)R a , —N(R b )C(O)OR a , —N(R b )S(O) 2 R a , —N(R b )C(O)NR a R b , —N(R b )S(O) 2 NR a R b , haloalkyl, cyanoalkyl, nitroalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylenyl-OC(O)alkyl, -alkylenyl-OC(O)Oalkyl, -alkylenyl-OS(O) 2 alkyl, -alkylenyl-S(alkyl), -alkylenyl-S(O)alkyl, -alkylenyl-S(O) 2 alkyl, -alkylenyl-S(O) 2 OR a , -alkylenyl-S(O) 2 NR a R b , -alkylenyl-C(O)R a , -alkylenyl-C(O)OR a , -alkylenyl-C(O)NR a R b , -alkylenyl-NR a R b , -alkylenyl-NOR a , -alkylenyl-N(R b )C(O)R a , -alkylenyl-N(R b )C(O)OR a , -alkylenyl-N(R b )S(O) 2 R a , -alkylenyl-N(R b )C(O)NR a R b , and -alkylenyl-N(R b )S(O) 2 NR a R b ;

R a at each occurrence is independently selected from the group consisting of hydrogen, alkyl, alkenyl and haloalkyl, and

R b at each occurrence is independently selected from the group consisting of hydrogen and alkyl.

2. The compound of claim 1 wherein R 1 is selected from the group consisting of hydrogen, unsubstituted and substituted aryl and unsubstituted and substituted heteroaryl.

3. The compound of claim 1 wherein and R 1 is selected from the group consisting of hydrogen and unsubstituted and substituted aryl.

4. The compound of claim 1 wherein R 1 is selected from the group consisting of hydrogen, and unsubstituted and substituted phenyl.

5. The compound of claim 1 wherein R 1 is selected from the group consisting of hydrogen, unsubstituted and substituted phenyl and unsubstituted and substituted pyridinyl.

6. The compound of claim 1 wherein R 1 is hydrogen.

7. The compound of claim 1 wherein R 1 is hydrogen, and R 4 is unsubstituted and substituted heterocycle.

8. The compound of claim 1 wherein R 1 is hydrogen, and R 4 is a heterocycle ring selected from the group consisting of piperidinyl, pyrrolidinyl, 1,2,3,4-tetrahydroisoquinolin-2-yl, 5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl, 5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl, piperazinyl, morpholinyl, and 1,3-thiazolidin-3-yl, each of which is independently unsubstituted or substituted.

9. The compound of claim 7 selected from the group consisting of

2-{[trans-5-amino-4-(2,4,5-trifluorophenyl)cyclohex-1-en-1-yl]carbonyl}-1,2,3,4-tetrahydroisoquinoline-7-carboxamide;

1-{[trans-5-amino-4-(2,4,5-trifluorophenyl)cyclohex-1-en-1-yl]carbonyl}piperidine-4-carboxamide;

trans-3-{[2-(trifluoromethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]carbonyl}-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-amine;

trans-3-{[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]carbonyl}-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-amine;

trans-3-(piperidin-1-ylcarbonyl)-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-amine;

trans-3-(morpholin-4-ylcarbonyl)-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-amine;

(1R,6S)-3-{[2-(trifluoromethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]carbonyl}-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-amine;

(1S,6R)-3-{[2-(trifluoromethyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]carbonyl}-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-amine;

trans-3-{[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]carbonyl}-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-amine;

trans-3-(piperazin-1-ylcarbonyl)-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-amine;

(1S,6R)-3-{[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]carbonyl}-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-amine;

(1S,6R)-3-(1,3-thiazolidin-3-ylcarbonyl)-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-amine; and

(1S,6R)-3-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)-6-(2,4,5-trifluorophenyl)cyclohex-3-en-1-amine;

or a pharmaceutically acceptable salt, prodrug, salt of a prodrug or a combination thereof.

10. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) of claim 1 in combination with a pharmaceutically suitable carrier.