Carboxamide compounds and their use as calpain inhibitors

1. A carboxamide compound of the formula (I-A.a′)

in which

R 1 is hydrogen, C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -alkynyl, where the last 3 radicals mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents R 1a , C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, where two adjacent C atoms may form a double bond, where the cycloalkyl moiety may further have 1, 2, 3 or 4 radicals R 1b , aryl, aryl-C 1 -C 6 -alkyl, or aryl-C 2 -C 6 -alkenyl, where aryl in the last 3 radicals mentioned may be unsubstituted or carry 1, 2, 3 or 4 identical or different radicals R 1c ; where

R 1a is selected independently of one another from OH, SH, COOH, CN, OCH 2 COOH, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 3 -C 7 -cycloalkyloxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, COOR a1 , CONR a2 R a3 , SO 2 NR a2 R a3 , —NR a2 —SO 2 —R a4 , NR a2 —CO—R a5 , SO 2 —R a4 , or NR a6 R a7 ,

R 1b is selected independently of one another from OH, SH, COOH, CN, OCH 2 COOH, halogen, phenyl which optionally has 1, 2 or 3 substituents R 1d , or C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, where the alkyl moieties in the last 3 substituents mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents R 1a , COOR b1 , CONR b2 R b3 , SO 2 NR b2 R b3 , NR b2 SO 2 —R b4 , NR b2 -CO—R b5 , SO 2 —R b4 , or NR b6 R b7 ,

in addition two R 1b radicals may together form a C 1 -C 4 -alkylene group, or 2 R 1b radicals bonded to adjacent C atoms of cycloalkyl may form together with the carbon atoms to which they are bonded also a benzene ring,

R 1c is selected independently of one another from OH, SH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , CH 2 F, O—CF 3 , O—CHF 2 , O—CH 2 F, COOH, OCH 2 COOH, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkylthio, where the alkyl moieties in the last 4 substituents mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents R 1a , C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, C 3 -C 7 -cycloalkyloxy, where the cycloalkyl moiety of the last three radicals mentioned may have 1, 2, 3 or 4 R 1b radicals,

aryl, O-aryl, O—CH 2 -aryl, where the last two radicals mentioned are unsubstituted in the aryl moiety or may carry 1, 2, 3 or 4 radicals R 1d ,

COOR c1 , CONR c2 R c3 , SO 2 NR c2 R c3 , NR c2 —SO 2 —R c4 , NR c2 -CO—R c5 , SO 2 —R c4 ,

—(CH 2 ) p —NR c6 R c7 with p=0, 1, 2, 3, 4, 5 or 6 and

O—(CH 2 ) q —NR c6 R c7 with q=2, 3, 4, 5 or 6; where

R a1 , R b1 and R c1 are independently of one another H, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkyl which has 1, 2 or 3 substituents selected from C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkoxy, or C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, aryl, or aryl-C 1 -C 4 -alkyl, where aryl in the last 2 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R 1d ,

R a2 , R b2 and R c2 are independently of one another H, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkyl which has 1, 2 or 3 substituents selected from C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkoxy, or C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, aryl, or aryl-C 1 -C 4 -alkyl, where aryl in the last 2 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R 1d , and

R a3 , R b3 and R c3 are independently of one another H, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkyl which has 1, 2 or 3 substituents selected from C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkoxy, or C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, aryl, or aryl-C 1 -C 4 -alkyl, where aryl in the last 2 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R 1d ,

R a4 , R b4 and R c4 are independently of one another C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkyl which has 1, 2 or 3 substituents selected from C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkoxy, or C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, aryl, or aryl-C 1 -C 4 -alkyl, where aryl in the last 2 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R 1d , and

R a5 , R b5 and R c5 have independently of one another one of the meanings mentioned for R a1 , R b1 and R c1 ;

R a6 , R b6 and R c6 are independently of one another H, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkyl which has 1, 2 or 3 substituents selected from C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkoxy, or C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 4 -cycloalkyl, C 3 -C 4 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, CO—C 1 -C 6 -alkyl, CO—O—C 1 -C 6 -alkyl, SO 2 —C 1 -C 6 -alkyl, aryl, O-aryl, OCH 2 -aryl, aryl-C 1 -C 4 -alkyl, CO-aryl, CO-(aryl-C 1 -C 4 -alkyl), CO—O-aryl, CO—O-(aryl-C 1 -C 4 -alkyl), SO 2 -aryl, or SO 2 -(aryl-C 1 -C 4 -alkyl), where aryl in the last 10 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R 1d , and

R a7 , R b7 and R c7 are independently of one another H, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkyl which has 1, 2 or 3 substituents selected from C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkoxy, or C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, aryl, or aryl-C 1 -C 4 -alkyl, where aryl in the last 2 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R 1d ,

or two radicals R 1b or R 1c bonded to adjacent C atoms form together with the C atoms to which they are bonded a 4, 5, 6 or 7-membered, optionally substituted carbocycle;

R 1d is selected from halogen, OH, SH, NO 2 , COOH, C(O)NH 2 , CHO, CN, NH 2 , OCH 2 COOH, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, CO—C 1 -C 6 -alkyl, CO—O—C 1 -C 6 -alkyl, NH—C 1 -C 6 -alkyl, NHCHO, NH—C(O)C 1 -C 6 -alkyl, and SO 2 —C 1 -C 6 -alkyl;

R 2 is C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, where two adjacent C atoms may form a double bond, where the cycloalkyl moiety may additionally have 1, 2, 3 or 4 R 2a radicals;

aryl, O-aryl, O—CH 2 -aryl, aryl-C 1 -C 6 -alkyl, or aryl-C 2 -C 6 -alkenyl, where aryl in the last 5 radicals mentioned may be unsubstituted or carry 1, 2, 3 or 4 identical or different R 2b radicals; where

R 2a has one of the meanings indicated for R 1b , and

R 2b has one of the meanings indicated for R 1c ;

R 3 is hydrogen or C 1 -C 4 -alkyl;

X is a radical of the formulae C(═O)—O—R x1 , C(═O)—NR x2 R x3 , C(═O)—N(R x4 )—(C 1 -C 6 alkylene)-NR x2 R x3 or C(═O)—N(R x4 )NR x2 R x3 , in which

R x1 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkyl which has 1, 2 or 3 substituents R xa , or C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 6 alkoxy-C 1 -C 4 -alkyl, where alkyl, alkenyl, alkoxy, alkynyl, cycloalkyl, in the last 5 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R xa , or aryl, or aryl-C 1 -C 4 -alkyl, where aryl in the last 2 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R x1 ,

R x2 is H, OH, CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkyl which has 1, 2 or 3 substituents R xa , or C 2 -C 6 alkenyl, C 2 -C 6 alkenyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 6 alkoxy-C 1 -C 4 -alkyl, CO—C 1 -C 6 alkyl, CO—O—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, O—C 1 -C 6 -alkyl, where alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, in the last 9 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R xa , aryl, O-aryl, O—CH 2 -aryl, aryl-C 1 -C 4 -alkyl, CO-aryl, CO-(aryl-C 1 -C 4 -alkyl), CO—O-aryl, CO—O-(aryl-C 1 -C 4 -alkyl), SO 2 -aryl, or SO 2 -(aryl-C 1 -C 4 -alkyl), where aryl in the last 10 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R x1 , and

R x3 is H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkyl which has 1, 2 or 3 substituents R xa , or C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 6 alkoxy-C 1 -C 4 -alkyl, where alkyl, alkenyl, alkoxy, alkynyl, cycloalkyl, in the last 5 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R xa , aryl, or aryl-C 1 -C 4 -alkyl, where aryl in the last 2 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R x1 ,

R x4 is H, OH, CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkyl which has 1, 2 or 3 substituents R xa , or C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, CO—C 1 -C 6 -alkyl, CO—O—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, where alkyl, alkenyl, alkoxy, alkynyl, cycloalkyl, in the last 8 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R xa ,

aryl, O-aryl, O—CH 2 -aryl, aryl-C 1 -C 4 -alkyl, CO-aryl, CO-(aryl-C 1 -C 4 -alkyl), CO—O-aryl, CO—O-(aryl-C 1 -C 4 -alkyl), SO 2 -aryl, or SO 2 -(aryl-C 1 -C 4 -alkyl) where aryl in the last 10 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R x1 , and

where R xa has one of the meanings indicated for R 1a , R xb has one of the meanings indicated for R 1b , and R xd has one of the meanings indicated for R 1d ;

n is 0, 1 or 2,

R y is selected independently of one another from OH, SH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , CH 2 F, O—CF 3 , O—CHF 2 , O—CH 2 F, COOH, OCH 2 COOH, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, C 1 -C 6 -alkylthio, where the last 4 radicals mentioned may be partly or completely halogenated and/or have 1, 2 or 3 substituents R ya ,

C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, C 3 -C 7 -cycloalkyl-O, where the cycloalkyl moiety in the last three radicals mentioned may have 1, 2, 3 or 4 R yb radicals,

aryl, O-aryl, CH 2 -aryl, O—CH 2 -aryl, where the last 3 radicals mentioned are unsubstituted in the aryl moiety or may carry 1, 2, 3 or 4 radicals R yd ,

COOR y1 , CONR y2 R y3 , SO 2 NR y2 R y3 , —NH—SO 2 —R y4 ,

NH—CO—R y5 , SO 2 —R y4 ,

—(CH 2 ) p —NR y6 R y7 with p=0, 1, 2, 3, 4, 5 or 6 and

O—(CH 2 ) q —NR y6 R y7 with q=2, 3, 4, 5 or 6;

or two R y radicals bonded to adjacent C atoms form together with the C atoms to which they are bonded a 4, 5, 6 or 7-membered, optionally substituted carbocycle, where

R ya has one of the meanings indicated for R 1a ,

R yb has one of the meanings indicated for R 1b ,

R yd has one of the meanings indicated for R 1d ,

R y1 has one of the meanings indicated for R c1 ,

R y2 has one of the meanings indicated for R c2 ,

R y3 has one of the meanings indicated for R c3 ,

R y4 has one of the meanings indicated for R c4 ,

R y5 has one of the meanings indicated for R c5 ,

R y6 has one of the meanings indicated for R c6 , and

R y7 has one of the meanings indicated for R c7 ;

m is 0 or 1, and

R w is selected from OH, F, Cl, CN, CF 3 , C 1 -C 6 -alkyl which is unsubstituted or may have 1, 2 or 3 substituents R wa , or C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy and C 3 -C 7 -cycloalkyl;

or two R w radicals bonded to adjacent C atoms form together with the C atoms to which they are bonded a 4, 5, 6 or 7-membered, optionally substituted carbocycle, where

R wa has one of the meanings indicated for R 1a ;

or a tautomer thereof, or a pharmaceutically acceptable salt thereof.

2. The carboxamide compound of claim 1 , in which X is a C(═O)—NR x2 R x3 radical.

3. The carboxamide compound of claim 2 , in which

R x2 is H, OH, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkyl which has 1, 2 or 3 substituents R xa , C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy-C 1 -C 4 -alkyl, aryl, or aryl-C 1 -C 4 -alkyl, where aryl in the last 2 radicals mentioned are unsubstituted or have 1, 2 or 3 substituents R xd , and

R x3 is H, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl or C 1 -C 6 -alkyl which has 1, 2 or 3 substituents R xa ,

in which R x5 is hydrogen or has the meaning indicated in claim 1 for R xb .

4. The carboxamide compound of claim 3 , in which X is C(O)—NH 2 .

5. The carboxamide compound of claim 1 , in which R 1 is phenyl-C 1 -C 4 -alkyl, where phenyl may be unsubstituted or carry 1, 2, 3 or 4 identical or different radicals R 1c .

6. The carboxamide compound of claim 1 , in which R 2 is selected from:

aryl, aryl-C 1 -C 6 -alkyl, and aryl-C 2 -C 6 -alkenyl, where aryl in the last 3 radicals mentioned may be unsubstituted or carry 1, 2, 3 or 4 identical or different radicals R 2b .

7. The carboxamide compound of claim 6 , in which R 2 is selected from aryl, where aryl may be unsubstituted or carry 1, 2, 3 or 4 identical or different radicals R 2b .

8. The carboxamide compound of claim 1 , in which W is selected from OH, F, Cl, NH 2 , CN, CF 3 , —CHF 2 , O—CF 3 , O—CHF 2 , O—CH 2 F, C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 1 -C 6 -alkylamino, C 1 -C 6 -dialkylamino, C 1 -C 4 alkoxy, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, CONR y2 R y3 , SO 2 NR y2 R y3 , —NH—SO 2 —R y4 , —(CH 2 ) p —NR y6 R y7 , NH—CO—R y5 , in which p is 1, 2, 3, 4, or 5, and R y2 , R y3 , R y4 , R y5 , R y6 , R y7 are H or C 1 -C 6 -alkyl, phenyl, benzyl, and O-benzyl, where the phenyl ring in the last 3 groups mentioned may have 1, 2 or 3 substituents selected from halogen, OH, SH, NO 2 , COOH, C(O)NH 2 , CHO, CN, NH 2 , OCH 2 COOH, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, CO—C 1 -C 6 -alkyl, CO—O—C 1 -C 6 -alkyl, NH—C 1 -C 6 -alkyl, NHCHO, NH—C(O)C 1 -C 6 -alkyl, and SO 2 —C 1 -C 6 -alkyl.

9. The carboxamide compound of claim 1 , which has the S configuration at the carbon atom carrying the group R 1 .

10. A pharmaceutical composition comprising the compound of claim 1 , or a tautomer or pharmaceutically acceptable salt thereof, and a pharmaceutical carrier.

11. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

N-[1-[2-(Aminocarbonyl)-1,3-dioxolan-2-yl]-2-(4-fluorophenyl)ethyl]-2-[3-(2,4-dichlorophenyl)-1H-pyrazol-1-yl]nicotinamide;

N-{1-[2-(Aminocarbonyl)-1,3-dioxolan-2-yl]-2-phenylethyl}-2-{3-[3-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}nicotinamide;

N-{1-[2-(Aminocarbonyl)-1,3-dioxolan-2-yl]-2-phenylethyl}-2-[3-(4-fluorophenyl)-1H-pyrazol-1-yl]nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-pentyl]-2-(4-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-(4-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-pentyl]-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-5-chloro-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-pentyl]-5-chloro-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-3-methyl-butyl]-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-3-methyl-butyl]-5-chloro-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-pentyl]-2-[3-(4-fluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(4-diethylamino-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-pentyl]-2-[3-(4-diethylaminomethyl-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-pentyl]-2-[3-(4-diethylamino-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-pentyl]-2-[3-(4-methoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-chloro-phenyl)-ethyl]-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-5-fluoro-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2-chloro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(4-cyano-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-cyclohexyl-ethyl]-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-chloro-phenyl)-ethyl]-2-[3-(4-fluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(3-chloro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2-chloro-4-fluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2-fluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2,4-dichloro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-methoxy-phenyl)-ethyl]-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-methoxy-phenyl)-ethyl]-2-[3-(4-fluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-5-cyano-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-(4-methyl-3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2,6-difluoro-phenyl)-pyrazol-1-yl]nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-(3-methyl-4-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(4-isopropyl-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2-methoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(3,5-difluoro-phenyl)-pyrazol-1-yl]nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-methoxy-phenyl)-ethyl]-2-[3-(2-fluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-(3-o-tolyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2,4-difluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2,6-dichloro-phenyl)-pyrazol-1-yl]-nicotinamide;

2-[3-(3-Benzyloxy-phenyl)-pyrazol-1-yl]-N-[1-(2-carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-methoxy-phenyl)-ethyl]-2-[3-(2,4-difluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-methoxy-phenyl)-ethyl]-2-[3-(2,4-dichloro-phenyl)-pyrazol-1-yl]nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-(4-phenyl-pyrazol-1-yl)-nicotinamide;

N—[(S)-1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N—[(S)-1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(4-fluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-(3-naphthalen-1-yl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-m ethoxy-phenyl)-ethyl]-2-[3-(2-chloro-4-fluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2,5-dichloro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2,3-dichloro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2,4,6-trifluoro-phenyl)-pyrazol-1-yl]nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2,4-dimethoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2,3-dichloro-6-fluoro-phenyl)-pyrazol-1-yl]nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2-methoxy-3,5-dimethyl-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[2-(4-Bromo-phenyl)-1-(2-carbamoyl-[1,3]dioxolan-2-yl)-ethyl]-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-fluoro-phenyl)-ethyl]-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2-trifluoromethoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(4-fluoro-2-methoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-methoxy-phenyl)-ethyl]-2-[3-(3-trifluoromethyl-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[2-(4-Benzyloxy-phenyl)-1-(2-carbamoyl-[1,3]dioxolan-2-yl)-ethyl]-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(5-fluoro-2-methoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(5-chloro-2-methoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-trifluoromethoxy-phenyl)-ethyl]-2-(3-phenyl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-methoxy-phenyl)-ethyl]-2-(3-naphthalen-1-yl-pyrazol-1-yl)-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-methoxy-phenyl)-ethyl]-2-[3-(4-fluoro-2-methoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(4-chloro-2-methoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2-chloro-3-fluoro-phenyl)-pyrazol-1-yl]nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-fluoro-phenyl)-ethyl]-2-[3-(3-trifluoromethyl-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2,5-dimethoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-fluoro-phenyl)-ethyl]-2-[3-(2-trifluoromethoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-methoxy-phenyl)-ethyl]-2-[3-(2,3-dichloro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-fluoro-phenyl)-ethyl]-2-[3-(2-chloro-3-fluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-methoxy-phenyl)-ethyl]-2-[3-(2-chloro-3-fluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(4-fluoro-phenyl)-ethyl]-2-[3-(2,3-dichloro-phenyl)-pyrazol-1-yl]nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-(3-fluoro-phenyl)-ethyl]-2-[3-(2-trifluoromethoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(2-difluoromethoxy-phenyl)-pyrazol-1-yl]nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(3-trifluoromethoxy-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[2-(4-Bromo-phenyl)-1-(2-carbamoyl-[1,3]dioxolan-2-yl)-ethyl]-2-[3-(4-fluoro-phenyl)-pyrazol-1-yl]nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[4-chloro-3-(4-fluoro-phenyl)-pyrazol-1-yl]nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-[3-(4-fluoro-phenyl)-4-(methanesulfonylamino-methyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-5-cyano-2-[3-(2-fluoro-phenyl)-pyrazol-1-yl]-nicotinamide;

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-(3-cyclohexyl-pyrazol-1-yl)-nicotinamide;

2-(3-Adamantan-1-yl-pyrazol-1-yl)-N-[1-(2-carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-nicotinamide;

2-(3-tert-Butyl-pyrazol-1-yl)-N-[1-(2-carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-nicotinamide; and

N-[1-(2-Carbamoyl-[1,3]dioxolan-2-yl)-2-phenyl-ethyl]-2-(4-fluoro-3-phenyl-pyrazol-1-yl)-nicotinamide.