Nonpeptide somatostatin type 5 receptor agonists and uses thereof
Described herein are compounds that are somatostatin modulators, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of somatostatin activity.
1. A compound of Formula (I), or a pharmaceutically acceptable salt, or solvate thereof:
wherein:
Ring A is carbocycle or heterocycle;
X is N or C—R a ; Y is N or C—R b ; Z is N or C—R c ;
R a , R b , and R c are each independently hydrogen, halogen, —CN, —N(R 9 ) 2 , —OR f , —CO 2 R 9 , —C(═O)N(R 9 ) 2 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 1 -C 6 fluoroalkoxy, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, or substituted or unsubstituted monocyclic heterocycle;
R f is -L 1 -R g ;
L 1 is absent, C 1 -C 6 alkylene, C 1 -C 6 fluoroalkylene, or C 1 -C 6 heteroalkylene;
R g is hydrogen, substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted phenyl, —CO 2 R 9 , or —C(═O)N(R 9 ) 2 , substituted or unsubstituted monocyclic heterocycle;
R 1 and R 2 are independently hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, or substituted or unsubstituted C 3 -C 5 heterocycloalkyl;
R 3 is hydrogen, —CN, —CO 2 R 9 , —C(═O)N(R 9 ) 2 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 fluoroalkoxy, or substituted or unsubstituted C 1 -C 6 heteroalkyl;
R 4 and R 5 are each independently hydrogen, halogen, —OR 9 , —N(R 9 ) 2 , —CN, —CO 2 R 9 , —C(═O)N(R 9 ) 2 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 1 -C 6 alkoxy, substituted or unsubstituted C 1 -C 6 fluoroalkoxy, or substituted or unsubstituted C 1 -C 6 heteroalkyl;
R 6 is substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 fluoroalkyl, substituted or unsubstituted C 1 -C 8 heteroalkyl, or -L 2 -R 6a ;
L 2 is absent, substituted or unsubstituted C 1 -C 8 alkylene, or —CHR 6b —;
R 6a is substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, or substituted or unsubstituted C 1 -C 9 heteroaryl;
R 6b is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, or substituted or unsubstituted C 3 -C 6 cycloalkyl;
R 7 is hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, or substituted or unsubstituted C 1 -C 9 heteroaryl;
or R 6 and R 7 are taken together with the nitrogen to which they are attached to form a substituted or unsubstituted N-containing heterocycle;
each R 8 , R 11 , and R 12 is independently hydrogen, halogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted monocyclic carbocycle, substituted or unsubstituted monocyclic heterocycle, —CN, —OR 9 , —C(═O)R 10 , —CO 2 R 9 , —C(═O)N(R 9 ) 2 , —N(R 9 ) 2 , —NR 9 C(═O)R 10 , —NR 9 C(═O)OR 10 , —NR 9 C(═O)N(R 9 ) 2 , —C(R 9 )═N—OR 9 , —SR 9 , —S(═O)R 9 , —SO 2 R 9 , or —SO 2 N(R 9 ) 2 ;
or R 11 is taken together with an adjacent R 8 and the atoms connecting the R 11 and the adjacent R 8 to form a fused substituted or unsubstituted carbocycle, or a fused substituted or unsubstituted heterocycle;
each R 9 is independently hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl;
or two R 9 on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycle;
each R 10 is independently substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted C 3 -C 7 cycloalkyl, substituted or unsubstituted monocyclic 3- to 8-membered heterocycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted monocyclic heteroaryl; and
n is 0-3.
2. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:
R 1 is hydrogen;
R 2 is hydrogen or C 1 -C 6 alkyl;
R 3 is hydrogen, C 1 -C 6 alkyl, or C 1 -C 6 fluoroalkyl; and
R 4 and R 5 are each independently hydrogen, halogen, C 1 -C 6 alkyl, or C 1 -C 6 fluoroalkyl.
3. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound has the structure of Formula (IIa), or a pharmaceutically acceptable salt, or solvate thereof:
wherein Ring A is phenyl, monocyclic heteroaryl or bicyclic heteroaryl.
4. The compound of claim 3 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound has the structure of Formula (IIIa), or a pharmaceutically acceptable salt, or solvate thereof:
5. The compound of claim 4 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound has the structure of Formula (VIa), or a pharmaceutically acceptable salt, or solvate thereof:
wherein:
R 3 is hydrogen or —CH 3 ;
R 8 is hydrogen or halogen;
R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, —CN, —OR 9 ;
R c is hydrogen, halogen, —CN, —N(R 9 ) 2 , —OR f , —CO 2 R 9 , —C(═O)N(R 9 ) 2 , C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, C 1 -C 6 fluoroalkoxy, or substituted or unsubstituted C 1 -C 6 heteroalkyl, substituted or unsubstituted monocyclic C 3 -C 6 cycloalkyl, substituted or unsubstituted monocyclic C 2 -C 5 heterocycloalkyl;
R f is -L 1 -R g ;
L 1 is absent, or C 1 -C 6 alkylene; and
R g is hydrogen, substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted phenyl, —CO 2 R 9 , —C(═O)N(R 9 ) 2 , substituted or unsubstituted monocyclic C 2 -C 5 heterocycloalkyl.
6. The compound of claim 3 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:
Ring A is pyrrolyl, furanyl, thiophenyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or triazinyl; and
n is 0, 1, or 2.
7. The compound of claim 3 , wherein:
Ring A is phenyl; or
Ring A is pyridinyl.
8. The compound of claim 3 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound has the structure of Formula (IVa-2), Formula (IVa-3), Formula (IVa-4), or Formula (IVa-5), or a pharmaceutically acceptable salt, or solvate thereof:
9. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:
each R 8 is independently hydrogen, halogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, —CN, —OR 9 , —CO 2 R 9 , —C(═O)N(R 9 ) 2 , —N(R 9 ) 2 , or —NR 9 C(═O)R 10 ; and
R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, —CN, —OR 9 , —CO 2 R 9 , —C(═O)N(R 9 ) 2 , —N(R 9 ) 2 , or —NR 9 C(═O)R 10 , or substituted or unsubstituted monocyclic carbocycle.
10. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:
each R 8 is independently hydrogen or halogen; and
R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, —CN, —OR 9 , or substituted or unsubstituted monocyclic cycloalkyl.
11. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:
R 7 is hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 1 -C 6 fluoroalkyl; and
R 6 is substituted or unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 fluoroalkyl, substituted or unsubstituted C 1 -C 8 heteroalkyl, or -L 2 -R 6a ;
L 2 is absent, substituted or unsubstituted C 1 -C 8 alkylene, or —CHR 6b —;
R 6a is substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, or substituted or unsubstituted C 1 -C 9 heteroaryl;
R 6b is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, or substituted or unsubstituted C 3 -C 6 cycloalkyl;
or R 6 and R 7 are taken together with the nitrogen to which they are attached to form a substituted or unsubstituted N-containing heterocycloalkyl.
12. The compound of claim 11 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:
R 7 is hydrogen or C 1 -C 6 alkyl; and
R 6 is C 1 -C 6 alkyl or C 1 -C 6 fluoroalkyl.
13. The compound of claim 11 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:
R 7 is hydrogen or C 1 -C 6 alkyl; and
R 6 is -L 2 -R 6a ;
R 6a is substituted or unsubstituted monocyclic C 2 -C 5 heterocycloalkyl, substituted or unsubstituted bridged C 5 -C 10 heterocycloalkyl, substituted or unsubstituted spirocyclic C 5 -C 10 heterocycloalkyl, substituted or unsubstituted monocyclic C 1 -C 5 heteroaryl or substituted or unsubstituted bicyclic C 6 -C 9 heteroaryl;
L 2 is absent, C 1 -C 4 alkylene, or —CHR 6b —; and
R 6b is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, or substituted or unsubstituted C 3 -C 6 cycloalkyl.
14. The compound of claim 13 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:
L 2 is absent, —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, or —CHR b6 —;
R 6a is substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted azetidine, or substituted or unsubstituted oxetanyl;
R 6b is hydrogen, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CHF 2 , —CH 2 F, —CF 3 , cyclopropyl, or cyclobutyl.
15. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:
X is CH;
Y is N;
Z is C—R c ;
R c is hydrogen, —CN, —CH 3 , —CF 3 , —OCH 3 , —OCF 3 , —CO 2 CH 3 , —C(═O)NH 2 , —C(═O)NHCH 3 , or —C(═O)N(CH 3 ) 2 ;
R 1 is hydrogen;
R 2 is hydrogen;
R 3 is hydrogen, —CH 3 , —CH 2 OH, —CH 2 OCH 3 , —CH 2 CH 2 F, —CH 2 CHF 2 , or —CH 2 CF 3 ;
R 4 is hydrogen or F;
R 5 is hydrogen or F;
R 6 is C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, or -L 2 -R 6a ;
L 2 is absent, C 1 -C 6 alkylene or —CHR 6b —;
R 6a is substituted or unsubstituted monocyclic C 3 -C 4 cycloalkyl, substituted or unsubstituted monocyclic or bicyclic C 5 -C 10 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, substituted or unsubstituted monocyclic C 2 -C 3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic C 4 -C 10 heterocycloalkyl, or substituted or unsubstituted C 1 -C 9 heteroaryl;
R 6b is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, or substituted or unsubstituted monocyclic C 3 -C 4 cycloalkyl;
R 7 is hydrogen or C 1 -C 6 alkyl;
or R 6 and R 7 are taken together with the nitrogen to which they are attached to form a substituted or unsubstituted heterocycle.
16. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound has the structure of Formula (VIII), or a pharmaceutically acceptable salt, or solvate thereof:
wherein:
Ring A is phenyl or pyridinyl;
R a and R c are each independently hydrogen, halogen, —CN, —N(R 9 ) 2 , —OR f , —CO 2 R 9 , —C(═O)N(R 9 ) 2 , C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, C 1 -C 6 fluoroalkoxy, substituted or unsubstituted monocyclic C 3 -C 6 cycloalkyl, or substituted or unsubstituted monocyclic C 2 -C 5 heterocycloalkyl;
R f is -L 1 -R g ;
L 1 is absent, or C 1 -C 6 alkylene;
R g is hydrogen, substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted phenyl, —CO 2 R 9 , or —C(═O)N(R 9 ) 2 , or substituted or unsubstituted monocyclic C 2 -C 5 heterocycloalkyl;
R 1 is hydrogen;
R 2 is hydrogen or C 1 -C 6 alkyl;
R 3 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl or C 1 -C 4 heteroalkyl;
R 4 is hydrogen, halogen, C 1 -C 4 alkyl, or C 1 -C 4 fluoroalkyl;
R 5 is hydrogen, halogen, C 1 -C 4 alkyl, or C 1 -C 4 fluoroalkyl;
R 6 is C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, or -L 2 -R 6a ;
L 2 is absent, C 1 -C 6 alkylene or —CHR 6b —;
R 6a is substituted or unsubstituted monocyclic C 3 -C 4 cycloalkyl, substituted or unsubstituted monocyclic or bicyclic C 5 -C 10 cycloalkyl, substituted or unsubstituted C 6 -C 10 aryl, substituted or unsubstituted monocyclic C 2 -C 3 heterocycloalkyl, substituted or unsubstituted monocyclic or bicyclic C 4 -C 10 heterocycloalkyl, or substituted or unsubstituted C 1 -C 9 heteroaryl;
R 6b is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, or substituted or unsubstituted monocyclic C 3 -C 4 cycloalkyl;
R 7 is hydrogen or C 1 -C 6 alkyl;
each R 8 is independently hydrogen, halogen, C 1 -C 6 alkyl, or C 1 -C 6 fluoroalkyl;
R 11 and R 12 are each independently hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, —CN, —OR 9 , —CO 2 R 9 , —C(═O)N(R 9 ) 2 , —N(R 9 ) 2 , or —NR 9 C(═O)R 10 , or substituted or unsubstituted monocyclic C 3 -C 8 cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic C 2 -C 5 heterocycloalkyl, or substituted or unsubstituted monocyclic C 1 -C 5 heteroaryl;
each R 9 is independently hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 1 -C 6 fluoroalkyl;
or two R 9 on the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted N-containing heterocycle; and
each R 10 is independently substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted C 1 -C 6 fluoroalkyl,
n is 0-3.
17. The compound of claim 16 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:
R 3 is hydrogen or —CH 3 ;
R 4 and R 5 are each hydrogen;
each R 8 is independently hydrogen or halogen; and
R 11 and R 12 are each independently hydrogen, halogen, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, —CN, —OR 9 .
18. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound has the structure of Formula (VIa), or a pharmaceutically acceptable salt, or solvate thereof:
wherein:
R c is hydrogen, —CN, —CH 3 , —CF 3 , —OCH 3 , —OCF 3 , —CO 2 CH 3 , —C(═O)NH 2 , —C(═O)NHCH 3 , or —C(═O)N(CH 3 ) 2 ;
R 3 is hydrogen or —CH 3 ;
R 6 is C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, or -L 2 -R 6a ;
L 2 is absent, —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, or —CHR 6b —;
R 6a is substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted azetidine, or substituted or unsubstituted oxetanyl;
R 6b is hydrogen, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CHF 2 , —CH 2 F, —CF 3 , cyclopropyl, or cyclobutyl;
R 7 is hydrogen or C 1 -C 6 alkyl;
R 8 is hydrogen, —F, or —Cl;
R 11 is hydrogen, —F, —Cl, —CN, —CH 3 , —CF 3 , —OCH 3 , —OCF 3 , or —OCHF 2 ; and
R 12 is hydrogen, —F, —Cl, —CN, —CH 3 , —CF 3 , —OCH 3 , —OCF 3 , or —OCHF 2 .
19. The compound of claim 18 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound has the structure of Formula (VIa-1), or a pharmaceutically acceptable salt, or solvate thereof:
wherein:
R 6 is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH(CH 3 )(CH 2 CH 3 ), —CH(CH 2 CH 3 )(CH 2 CH 3 ), —CH(CH 2 CH 2 CH 3 )(CH 2 CH 3 ), —C(CH 3 )(CHCH 3 ) 2 , —C(CH 3 ) 3 , —CH 2 F, —CHF 2 , —CF 3 , —CH 2 CF 3 , —CH(CF 3 )(CH 3 ), —CH(CF 3 )(CH 2 CH 3 ), —CH 2 CF 2 CH 3 , or —CH(CH 3 )(CH 2 CF 3 );
R 7 is hydrogen or —CH 3 ;
R 11 is —F or —Cl; and
R 12 is —F or —Cl.
20. The compound of claim 18 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound has the structure of Formula (VIa-1), or a pharmaceutically acceptable salt, or solvate thereof:
wherein:
R 6 is -L 2 -R 6a ;
R 7 is hydrogen or —CH 3 ;
R 11 is —F or —Cl; and
R 12 is —F or —Cl.
21. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound has the structure of Formula (VIb), or a pharmaceutically acceptable salt, or solvate thereof:
wherein:
R c is hydrogen, —CN, —CH 3 , —CF 3 , —OCH 3 , —OCF 3 , —CO 2 CH 3 , —C(═O)NH 2 , —C(═O)NHCH 3 , or —C(═O)N(CH 3 ) 2 ;
R 3 is hydrogen or —CH 3 ;
R 6 is C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, or -L 2 -R 6a ;
L 2 is absent, —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, or —CHR 6b —;
R 6a is substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted azetidine, or substituted or unsubstituted oxetanyl;
R 6b is hydrogen, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CHF 2 , —CH 2 F, —CF 3 , cyclopropyl, or cyclobutyl;
R 7 is hydrogen or C 1 -C 6 alkyl;
R 8 is hydrogen, —F, or —Cl;
R 11 is hydrogen, —F, —Cl, —CN, —CH 3 , —CF 3 , —OCH 3 , —OCF 3 , or —OCHF 2 ; and
R 12 is hydrogen, —F, —Cl, —CN, —CH 3 , —CF 3 , —OCH 3 , —OCF 3 , or —OCHF 2 .
22. The compound of claim 21 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound has the structure of Formula (VIb-1), or a pharmaceutically acceptable salt, or solvate thereof:
wherein:
R 6 is -L 2 -R 6a ;
R 7 is hydrogen or —CH 3 ;
R 11 is —F or —Cl; and
R 12 is —F or —Cl.
23. The compound of claim 21 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound has the structure of Formula (VIb-1), or a pharmaceutically acceptable salt, or solvate thereof:
wherein:
R 6 is —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH 2 CH 2 CH 3 , —CH 2 CH(CH 3 ) 2 , —CH(CH 3 )(CH 2 CH 3 ), —CH(CH 2 CH 3 )(CH 2 CH 3 ), —CH(CH 2 CH 2 CH 3 )(CH 2 CH 3 ), —C(CH 3 )(CHCH 3 ) 2 , —C(CH 3 ) 3 , —CH 2 F, —CHF 2 , —CF 3 , —CH 2 CF 3 , —CH(CF 3 )(CH 3 ), —CH(CF 3 )(CH 2 CH 3 ), —CH 2 CF 2 CH 3 , or —CH(CH 3 )(CH 2 CF 3 );
R 7 is hydrogen or —CH 3 ;
R 11 is —F or —Cl; and
R 12 is —F or —Cl.
24. A compound selected from:
1-1: 4-[(3 S)-3-aminopyrrolidin-1-yl]-N,5-bis(3,5-dimethylphenyl)pyridine-3-carboxamide;
1-3: 4-[(3 S)-3-aminopyrrolidin-1-yl]-N-(3-chloro-5-fluorophenyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;
1-4: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-4-fluorophenyl)-N-(2-fluorophenyl)pyridine-3-carboxamide;
1-7: 4-[(3 S)-3-aminopyrrolidin-1-yl]-5-(3-cyanophenyl)-N-cyclohexylpyridine-3-carboxamide;
1-8: 4-[(3 S)-3-aminopyrrolidin-1-yl]-5-(3-cyanophenyl)-N-(1-methylcyclobutyl)pyridine-3-carboxamide;
1-9: 4-[(3 S)-3-aminopyrrolidin-1-yl]-N-benzyl-5-(3-cyanophenyl)pyridine-3-carboxamide;
1-10: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyanophenyl)-N-(4,4-difluorocyclohexyl)pyridine-3-carboxamide;
1-11: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-dimethylcyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;
1-12: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;
1-13: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;
1-14: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclohexyl)-5-(3,5-dimethylphenyl)pyridine-3-carboxamide;
1-15: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)-N-[1-(trifluoromethyl)cyclopentyl]pyridine-3-carboxamide;
1-16: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-17: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2,3-dihydro-1H-inden-1-yl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;
1-18: N-(adamantan-2-yl)-4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;
1-19: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-ethylcyclobutyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;
1-20: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,4,5-trifluorophenyl)pyridine-3-carboxamide;
1-21: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-22: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(3,3-dimethylcyclobutyl)pyridine-3-carboxamide;
1-23: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-24: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropylethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;
1-25: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(dicyclopropylmethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;
1-26: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-5-(3-fluoro-5-methylphenyl)pyridine-3-carboxamide;
1-27: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-fluoro-5-methylphenyl)-N-(1-methyl-1H-pyrazol-3-yl)pyridine-3-carboxamide;
1-28: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;
1-29: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-tert-butyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-30: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-31: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide;
1-32: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-methylcyclopropyl)methyl]pyridine-3-carboxamide;
1-33: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclobutylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-34: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(1-methylcyclobutyl)pyridine-3-carboxamide;
1-35: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(3,3-difluorocyclobutyl)pyridine-3-carboxamide;
1-37: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-38: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(3-methylbutan-2-yl)pyridine-3-carboxamide;
1-39: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,4-dimethylpentan-3-yl)pyridine-3-carboxamide;
1-40: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-cyclopropylpropan-2-yl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-41: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1 S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-42: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(2,2-difluorocyclopropyl)methyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-43: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2,2-dimethylcyclopropyl)methyl]pyridine-3-carboxamide;
1-44: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1R)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-45: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoro-3-methylbutan-2-yl)pyridine-3-carboxamide;
1-46: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-methylpropyl)pyridine-3-carboxamide;
1-47: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-fluorocyclobutyl)methyl]pyridine-3-carboxamide;
1-48: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-49: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-50: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(3,3-difluorocyclobutyl)methyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-51: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(dicyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-52: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[trans-2-fluorocyclohexyl]pyridine-3-carboxamide;
1-53: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-54: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2 S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-55: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(trans-3-fluorocyclobutyl]pyridine-3-carboxamide;
1-56: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclobutyl-2,2,2-trifluoroethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-57: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-methylbutyl)pyridine-3-carboxamide;
1-58: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2-ethylbutyl)pyridine-3-carboxamide;
1-59: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[cis-3-fluorocyclobutyl]pyridine-3-carboxamide;
1-60: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(4,4,4-trifluorobutan-2-yl)pyridine-3-carboxamide;
1-61: 4-[(3 S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(dicyclopropylmethyl)pyridine-3-carboxamide;
1-62: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-(2,2-difluoropropyl)pyri dine-3-carboxamide;
1-64: 4-[(3 S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-65: 4-[(3 S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3-fluorophenyl)pyridine-3-carboxamide;
1-66: 4-[(3 S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,4-difluorophenyl)pyridine-3-carboxamide;
1-67: 4-[(3 S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-68: 4-[(3 S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-69: 4-[(3 S)-3-aminopyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-70: 4-[(3 S)-3-aminopyrrolidin-1-yl]-6-cyano-N-(dicyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-71: 4-[(3 S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2 S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-72: 4-[(3 S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide;
1-73: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cycloheptyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-74: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;
1-76: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(pentan-3-yl)pyridine-3-carboxamide;
1-77: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-78: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclopentyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-79: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-80: 4-[(3 S)-3-aminopyrrolidin-1-yl]-3-(3,5-difluorophenyl)-5-(piperidine-1-carbonyl)pyridine-2-carbonitrile;
1-81: 4-[(3 S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-82: 4-[(3 S)-3-aminopyrrolidin-1-yl]-6-cyano-N-cyclopentyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-83: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[cis-2-fluorocyclohexyl]pyridine-3-carboxamide;
1-84: 4-[(3 S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-chlorophenyl)-6-cyanopyridine-3-carboxamide;
1-85: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2-methylpropyl)pyridine-3-carboxamide;
1-86: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(cyclopropylmethyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-87: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclobutyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-88: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(oxan-4-yl)pyridine-3-carboxamide;
1-89: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(oxan-3-yl)pyridine-3-carboxamide;
1-90: 4-[(3 S)-3-aminopyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-chloro-5-fluorophenyl)-6-cyanopyridine-3-carboxamide;
1-91: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(propan-2-yl)pyridine-3-carboxamide;
1-92: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;
1-93: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-94: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3-cyano-5-methoxyphenyl)pyridine-3-carboxamide;
1-95: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;
1-96: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]pyridine-3-carboxamide;
1-97: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-phenylethyl]pyridine-3-carboxamide;
1-98: 4-[(3S)-3-amino-3-(hydroxymethyl)pyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-101: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-103: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;
1-104: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-5-yl)methyl]pyridine-3-carboxamide;
1-105: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-3-yl)methyl]pyridine-3-carboxamide;
1-106: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-imidazol-2-yl)methyl]pyridine-3-carboxamide;
1-107: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1-methyl-1H-pyrazol-4-yl)methyl]pyridine-3-carboxamide;
1-108: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(pyrimidin-2-yl)methyl]pyridine-3-carboxamide;
1-109: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(4-benzylpiperazine-1-carbonyl)-3-(3,5-difluorophenyl)pyridine-2-carbonitrile;
1-110: 4-[(3 S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(3-phenylpropyl)pyridine-3-carboxamide;
1-111: 4-[(3 S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(1-phenylpiperidin-4-yl)pyridine-3-carboxamide;
1-112: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-113: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(2,2-dimethyloxan-4-yl)pyridine-3-carboxamide;
1-114: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;
1-115: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2-hydroxyphenyl)methyl]pyridine-3-carboxamide;
1-116: 4-[(3R)-3-amino-3-(methoxymethyl)pyrrolidin-1-yl]-6-cyano-N-[(1 S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-118: 4-[(3 S)-3-amino-3-(2,2-difluoroethyl)pyrrolidin-1-yl]-6-cyano-N-[(1 S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-120: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1 S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]pyridine-3-carboxamide;
1-122: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;
1-123: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-fluorophenyl)-N-[(1 S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;
1-124: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3-fluorophenyl)-6-methylpyridine-3-carboxamide;
1-125: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1 S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;
1-126: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(pyrimidin-2-yl)ethyl]pyridine-3-carboxamide;
1-127: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1 S)-1-cyclopropylethyl]-5-[3-(trifluoromethoxy)phenyl]pyridine-3-carboxamide;
1-130: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;
1-132: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(1,2-oxazol-3-yl)ethyl]pyridine-3-carboxamide;
1-133: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[1-(1-methyl-1H-1,2,3-triazol-4-yl)ethyl]pyridine-3-carboxamide;
1-135: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-137: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;
1-138: 4-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1S)-1-cyclopropylethyl]pyridine-3-carboxamide;
1-140: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-141: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;
1-143: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)-5-fluorophenyl]pyridine-3-carboxamide;
1-144: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;
1-145: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-3,3-difluorocyclopentyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;
1-146: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;
1-147: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-149: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]pyridine-3-carboxamide;
1-150: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;
1-151: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-152: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;
1-153: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;
1-154: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methoxy-5-[3-(trifluoromethoxy)phenyl]pyridine-3-carboxamide;
1-163: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(2,2-difluoro-2H-1,3-benzodioxol-4-yl)pyridine-3-carboxamide;
1-164: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-fluoro-5-(trifluoromethyl)phenyl]-6-methoxypyridine-3-carboxamide;
1-165: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)phenyl]-6-methoxypyridine-3-carboxamide;
1-168: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-[3-(difluoromethoxy)phenyl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-171: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-172: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide;
1-173: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide;
1-174: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methylpyridine-3-carboxamide;
1-175: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)pyridine-3-carboxamide;
1-176: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-ethoxypyridine-3-carboxamide;
1-177: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-(2,2-difluoroethoxy)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-178: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-(cyclopropylmethoxy)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-179: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2-methoxyethoxy)pyridine-3-carboxamide;
1-180: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-[3-(difluoromethoxy)-5-fluorophenyl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-181: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;
1-184: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(2,2-difluoro-2H-1,3-benzodioxol-4-yl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-188: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-189: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;
1-190: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide;
1-191: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyclopropoxy-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-192: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-193: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methoxy-N-[4-(trifluoromethyl)cyclohexyl]pyridine-3-carboxamide;
1-194: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(1-cyclopropyl-2,2,2-trifluoroethyl)-5-(3,5-difluorophenyl)-6-methoxypyridine-3-carboxamide;
1-195: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide;
1-196: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide;
1-197: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide;
1-198: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-(trifluoromethyl)pyridine-3-carboxamide;
1-199: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;
1-200: ethyl 2-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetate;
1-201: ethyl 3-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoate;
1-202: ethyl 4-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoate;
1-203: 2-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetic acid
1-204: 3-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoic acid;
1-205: 4-({4-[(3S)-3-aminopyrrolidin-1-yl]-5-[(4,4-difluorocyclohexyl)carbamoyl]-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoic acid;
1-209: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;
1-210: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;
1-211: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;
1-212: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-(trifluoromethyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-213: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-cyclohexyl-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;
1-214: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;
1-215: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-dichlorophenyl)-6-(trifluoromethyl)pyridine-3-carboxamide;
1-216: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-(trifluoromethyl)pyridine-3-carboxamide;
1-217: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-(trifluoromethyl)pyridine-3-carboxamide;
1-218: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-(cyclopropylmethyl)-5-(3,5-difluorophenyl)-N-methylpyridine-3-carboxamide;
1-219: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-N-methylpyridine-3-carboxamide;
1-222: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-223: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(1-hydroxycyclopentyl)methyl]-6-methylpyridine-3-carboxamide;
1-224: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropyl-2-hydroxyethyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;
1-225: 4-(3-aminopyrrolidin-1-yl)-6-cyano-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-carboxamide;
1-226: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-(1,1,1-trifluoropropan-2-yl)pyridine-3-carboxamide;
1-227: 4-[(3R)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-228: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-229: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;
1-230: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3,5-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-231: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-232: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-[3-(difluoromethoxy)phenyl]-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-233: 4-[(3S)-3-aminopyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)-6-methylpyridine-3-carboxamide;
1-234: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}pyridine-3-carboxamide;
1-235: (3S)-1-[3-(3,5-difluorophenyl)-2-methoxy-5-(piperidine-1-carbonyl)pyridin-4-yl]pyrrolidin-3-amine;
1-236: (3S)-1-[3-(3,5-difluorophenyl)-5-(4,4-difluoropiperidine-1-carbonyl)-2-methoxypyridin-4-yl]pyrrolidin-3-amine;
1-237: (3S)-1-[3-(3,5-difluorophenyl)-5-(3,3-difluoropiperidine-1-carbonyl)-2-methoxypyridin-4-yl]pyrrolidin-3-amine;
1-238: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;
1-239: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;
1-240: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;
1-241: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-[3-(difluoromethoxy)-5-fluorophenyl]-6-methoxy-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;
1-242: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;
1-243: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;
1-244: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1,2-oxazol-3-yl)methyl]pyridine-3-carboxamide;
1-245: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1S)-1-(pyridin-2-yl)ethyl]pyridine-3-carboxamide;
1-246: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-(2-hydroxyethoxy)pyridine-3-carboxamide;
1-247: 2-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)acetic acid;
1-259: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,4-difluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-260: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-chloro-3-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-261: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-262: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-methoxypyridine-3-carboxamide;
1-263: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-chloro-3-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;
1-264: 3-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)propanoic acid;
1-265: 4-({4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-{[(1S)-1-cyclopropylethyl]carbamoyl}-3-(3,5-difluorophenyl)pyridin-2-yl}oxy)butanoic acid;
1-266: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)-6-[(oxetan-3-yl)methoxy]pyridine-3-carboxamide;
1-267: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-(benzyloxy)-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-268: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-(4,4-difluorocyclohexyl)-6-methylpyridine-3-carboxamide;
1-269: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-(3,3-difluorocyclobutyl)-6-methylpyridine-3-carboxamide;
1-272: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;
1-273: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide;
1-275: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-276: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-277: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(4,4-difluorocyclohexyl)-6-methylpyridine-3-carboxamide;
1-278: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methylpyridine-3-carboxamide;
1-279: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,4-difluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-280: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-cyano-5-methoxyphenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;
1-281: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyclopropyl-N-(4,4-difluorocyclohexyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-282: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methoxypyridine-3-carboxamide;
1-283: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-284: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(4,4-difluorocyclohexyl)-6-methoxypyridine-3-carboxamide;
1-285: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-(3,3-difluorocyclobutyl)-6-methoxypyridine-3-carboxamide;
1-286: 4-[(3S)-3-aminopyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-N-{3-fluorobicyclo[1.1.1]pentan-1-yl}-6-methoxypyridine-3-carboxamide;
1-287: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-6-methyl-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-288: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(3,4-difluorophenyl)-6-methylpyridine-3-carboxamide;
1-289: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3-chloro-4-fluorophenyl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;
1-290: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyclopropyl-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-5: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2′-cyano-N-(3-methylphenyl)-[3,4′-bipyridine]-5-carboxamide;
1-6: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,5-dimethylphenyl)-2′-methyl-[3,4′-bipyridine]-5-carboxamide;
1-121: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(1-methyl-1H-pyrazol-3-yl)pyridine-3-carboxamide;
1-128: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(2-methyl-1,3-thiazol-5-yl)pyridine-3-carboxamide;
1-129: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-[(1S)-1-cyclopropylethyl]-2′-(trifluoromethyl)-[3,4′-bipyridine]-5-carboxamide;
1-131: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2′,6′-dimethyl-[3,4′-bipyridine]-5-carboxamide;
1-134: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(1,2-oxazol-4-yl)pyridine-3-carboxamide;
1-142: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5′-fluoro-[3,3′-bipyridine]-5-carboxamide;
1-148: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methyl-5-(1-methyl-1H-pyrazol-4-yl)pyridine-3-carboxamide;
1-155: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-6-methyl-5-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]pyridine-3-carboxamide;
1-156: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(1-cyclopropyl-1H-pyrazol-4-yl)-N-[(1S)-1-cyclopropylethyl]-6-methylpyridine-3-carboxamide;
1-157: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2′-methoxy-2-methyl-[3,4′-bipyridine]-5-carboxamide;
1-158: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5′-chloro-N-[(1S)-1-cyclopropylethyl]-2-methyl-[3,3′-bipyridine]-5-carboxamide;
1-159: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2-methyl-2′-(trifluoromethyl)-[3,4′-bipyridine]-5-carboxamide;
1-160: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5′-fluoro-2-methyl-[3,3′-bipyridine]-5-carboxamide;
1-166: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2-methoxy-2′-(trifluoromethyl)-[3,4′-bipyridine]-5-carboxamide;
1-167: 4-[(3 S)-3-amino-3-methylpyrrolidin-1-yl]-5′-chloro-N-[(1S)-1-cyclopropylethyl]-2-methoxy-[3,3′-bipyridine]-5-carboxamide;
1-169: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2′-(trifluoromethyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]-[3,4′-bipyridine]-5-carboxamide;
1-170: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2′-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]-[3,4′-bipyridine]-5-carboxamide;
1-185: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-methoxy-5-(2-methylpyrimidin-5-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-187: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-206: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2′-ethoxy-2-(trifluoromethyl)-[3,4′-bipyridine]-5-carboxamide;
1-208: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2′-methoxy-2-(trifluoromethyl)-[3,4′-bipyridine]-5-carboxamide;
1-248: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclopentyl-2′-(trifluoromethyl)-[3,4′-bipyridine]-5-carboxamide;
1-249: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-(pentan-3-yl)-2′-(trifluoromethyl)-[3,4′-bipyridine]-5-carboxamide;
1-250: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-(2-methylpropyl)-2′-(trifluoromethyl)-[3,4′-bipyridine]-5-carboxamide;
1-251: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-butyl-2-cyano-2′-(trifluoromethyl)-[3,4′-bipyridine]-5-carboxamide;
1-252: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclohexyl-2′-methoxy-[3,4′-bipyridine]-5-carboxamide;
1-253: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2′-methoxy-N-(pentan-3-yl)-[3,4′-bipyridine]-5-carboxamide;
1-254: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-N-cyclopentyl-2′-methoxy-[3,4′-bipyridine]-5-carboxamide;
1-255: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-2′-methoxy-2-methyl-[3,4′-bipyridine]-5-carboxamide;
1-256: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-2′-methoxy-2-methyl-[3,4′-bipyridine]-5-carboxamide;
1-257: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-2-methyl-2′-(trifluoromethyl)-[3,4′-bipyridine]-5-carboxamide;
1-258: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-2-methyl-2′-(trifluoromethyl)-[3,4′-bipyridine]-5-carboxamide;
1-270: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-cyano-2′-methoxy-N-(2-methylpropyl)-[3,4′-bipyridine]-5-carboxamide;
2-1: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-ethyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-2: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-(pyrrolidine-1-carbonyl)pyridin-4-yl]pyrrolidin-3-amine;
2-3: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-ethyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-4: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-5: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(oxolan-3-yl)pyridine-3-carboxamide;
2-6: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-phenylpyridine-3-carboxamide;
2-7: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;
2-8: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-methoxyethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-9: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(2-hydroxyethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-10: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(2,2,2-trifluoroethyl)pyridine-3-carboxamide;
2-11: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1.1.1-trifluoropropan-2-yl]pyridine-3-carboxamide;
2-12: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-13: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-5-(4-methyl-1H-1,3 benzodiazol-2-yl)pyridine-3-carboxamide;
2-14: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(1-cyclopropylethyl)-5-(4-methyl-1H-1,3 benzodiazol-2-yl)pyridine-3-carboxamide;
2-15: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(4-methyl 1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-16: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-17: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(4,4-difluorocyclohexyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-18: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2R)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
2-19: (3S)-1-[3-(3,3-dimethylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;
2-20: (3S)-1-[3-(2,2-dimethylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;
2-21: (3S)-1-[3-(3,3-dimethylazetidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;
2-22: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopropyl-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-23: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclopropylmethyl)-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-24: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-fluoro-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
2-25: (3S)-1-[3-(3,3-difluoropyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;
2-26: (3S)-1-(3-{2-azatricyclo[3.3.1.1 3,7 ]decane-2-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine;
2-27: (3S)-1-[3-(3-tert-butylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;
2-28: (3S)-1-{3-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl}-3-methylpyrrolidin-3-amine;
2-29: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-N-methyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-30: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(7-fluoro-4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
2-31: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(cyclobutylmethyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-32: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-(4,4,4-trifluorobutan-2-yl)pyridine-3-carboxamide;
2-33: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[2.2.1]heptan-1-yl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-34: (3S)-1-[3-(2,3-dihydro-1H-indole-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;
2-35: (3S)-1-(3-{2-azabicyclo[2.2.2]octane-2-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine;
2-36: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-[2-(propan-2-yl)pyrrolidine-1-carbonyl]pyridin-4-yl]pyrrolidin-3-amine;
2-37: (3S)-1-{3-[(3aR)-octahydrocyclopenta[b]pyrrole-1-carbonyl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl}-3-methylpyrrolidin-3-amine;
2-38: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridine-3-carboxamide;
2-39: (3S)-1-(3-{5-azaspiro[2.4]heptane-5-carbonyl}-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine;
2-40: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(4-methyl-1H-1,3-benzodiazol-2-yl)-N-[(2S)-1,1,1-trifluorobutan-2-yl]pyridine-3-carboxamide;
2-41: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-[(2S)-2-(trifluoromethyl)pyrrolidine-1-carbonyl]pyridin-4-yl]pyrrolidin-3-amine;
2-42: (3S)-1-[3-(3-cyclopropylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;
2-43: (3S)-1-[3-(2-cyclopropylpyrrolidine-1-carbonyl)-5-(4-methyl-1H-1,3-benzodiazol-2-yl)pyridin-4-yl]-3-methylpyrrolidin-3-amine;
2-44: (3S)-3-methyl-1-[3-(4-methyl-1H-1,3-benzodiazol-2-yl)-5-[3-(trifluoromethyl)pyrrolidine-1-carbonyl]pyridin-4-yl]pyrrolidin-3-amine;
2-45: (3S)-1-(3-{2-azatricyclo[3.3.1.1 3,7 ]decane-2-carbonyl}-5-(7-chloro-1H-1,3-benzodiazol-2-yl)pyridin-4-yl)-3-methylpyrrolidin-3-amine;
1-161: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(1-methyl-1H-indazol-6-yl)pyridine-3-carboxamide;
1-162: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-5-(1-methyl-1H-indazol-4-yl)pyridine-3-carboxamide;
1-182: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-methoxy-5-(1-methyl-1H-1,3-benzodiazol-6-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-183: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-methoxy-5-(1-methyl-1H-indazol-4-yl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-186: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(2,1,3-benzoxadiazol-5-yl)-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
1-2: 4-[(3R)-3-aminopyrrolidin-1-yl]-N,5-bis(3,5-dimethylphenyl)pyridine-3-carboxamide;
1-36: 4-[3-amino-3-(methoxymethyl)pyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-63: 4-[3-(1-aminoethyl)azetidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-75: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyanopyridine-3-carboxamide;
1-99: 4-[(3R)-3-amino-3-(hydroxymethyl)pyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-100: 4-[3-(1-aminoethyl)azetidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-102: 4-[(3S,4S)-3-amino-4-fluoropyrrolidin-1-yl]-N-{bicyclo[1.1.1]pentan-1-yl}-6-cyano-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-117: 4-[(3S)-3-amino-3-(methoxymethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-119: 4-[(3R)-3-amino-3-(2,2-difluoroethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-136: 4-[(3S,4S)-3-amino-4-fluoropyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-139: 4-[(3S,4S)-3-amino-4-fluoropyrrolidin-1-yl]-5-(3-chloro-5-fluorophenyl)-6-cyano-N-[(1S)-1-cyclopropylethyl]pyridine-3-carboxamide;
1-220: 4-[(3S)-3-amino-3-(fluoromethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-221: 4-[(3R)-3-amino-3-(fluoromethyl)pyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide;
1-274: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-bromo-6-methoxy-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide;
3-1: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-2-(3,5-difluorophenyl)pyridine-4-carboxamide;
3-2: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclohexyl-2-(3,5-difluorophenyl)pyridine-4-carboxamide;
3-3: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-(3,5-difluorophenyl)-N-[(1S)-1-phenylethyl]pyridine-4-carboxamide;
3-4: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(dicyclopropylmethyl)-2-(3,5-difluorophenyl)pyridine-4-carboxamide;
3-5: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-{bicyclo[2.2.1]heptan-1-yl}-2-(3,5-difluorophenyl)pyridine-4-carboxamide;
3-6: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cycloheptyl-2-(3,5-difluorophenyl)pyridine-4-carboxamide;
3-7: N-(adamantan-1-yl)-3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-2-(3,5-difluorophenyl)pyridine-4-carboxamide;
3-8: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-cyclopentyl-2-(3,5-difluorophenyl)pyridine-4-carboxamide;
4-1: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-chloro-N-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)pyridine-2-carboxamide;
4-2: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)-5-methylpyridine-2-carboxamide;
4-3: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-cyano-N-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)pyridine-2-carboxamide;
4-4: methyl 5-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-{[(1S)-1-cyclopropylethyl]carbamoyl}-4-(3,5-difluorophenyl)pyridine-3-carboxylate; and
4-5: 3-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N2-[(1S)-1-cyclopropylethyl]-4-(3,5-difluorophenyl)pyridine-2,5-dicarboxamide;
or a pharmaceutically acceptable salt, or solvate thereof.
25. The compound of claim 24 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound is:
1-30: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
26. The compound of claim 24 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound is:
1-54: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
27. The compound of claim 24 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound is:
1-71: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
28. The compound of claim 24 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound is:
1-77: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
29. The compound of claim 24 , or a pharmaceutically acceptable salt, or solvate thereof, wherein the compound is:
1-192: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
30. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, and at least one pharmaceutically acceptable excipient.
31. A pharmaceutical composition comprising a compound of claim 24 , or a pharmaceutically acceptable salt, or solvate thereof, and at least one pharmaceutically acceptable excipient.
32. The pharmaceutical composition of claim 31 , wherein the compound, or a pharmaceutically acceptable salt, or solvate thereof, is:
1-30: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
33. The pharmaceutical composition of claim 6 , wherein the compound, or a pharmaceutically acceptable salt, or solvate thereof, is:
1-54: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
34. The pharmaceutical composition of claim 31 , wherein the compound, or a pharmaceutically acceptable salt, or solvate thereof, is:
1-71: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
35. The pharmaceutical composition of claim 31 , wherein the compound, or a pharmaceutically acceptable salt, or solvate thereof, is:
1-77: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
36. The pharmaceutical composition of claim 31 , wherein the compound, or a pharmaceutically acceptable salt, or solvate thereof, is:
1-192: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
37. A method of treating hyperinsulinemia in a mammal comprising administering a compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, to the mammal in need thereof.
38. A method of treating hyperinsulinemia in a mammal comprising administering a compound of claim 24 , or a pharmaceutically acceptable salt, or solvate thereof, to the mammal in need thereof.
39. The method of claim 38 , wherein the compound, or a pharmaceutically acceptable salt, or solvate thereof, is:
1-30: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-N-(3,3-difluorocyclobutyl)-5-(3,5-difluorophenyl)pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
40. The method of claim 38 , wherein the compound, or a pharmaceutically acceptable salt, or solvate thereof, is:
1-54: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
41. The method of claim 38 , wherein the compound, or a pharmaceutically acceptable salt, or solvate thereof, is:
1-71: 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
42. The method of claim 38 , wherein the compound, or a pharmaceutically acceptable salt, or solvate thereof, is:
1-77: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-N-[(1S)-1-cyclopropylethyl]-5-(3,5-difluorophenyl)pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.
43. The method of claim 38 , wherein the compound, or a pharmaceutically acceptable salt, or solvate thereof, is:
1-192: 4-[(3S)-3-amino-3-methylpyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide, or a pharmaceutically acceptable salt, or solvate thereof.