Small molecule activators of nicotinamide phosphoribosyltransferase (NAMPT) and uses thereof

1. A compound of Formula (Ia), or a pharmaceutically acceptable salt, or solvate thereof:

wherein:

X is absent or -L 1 -X 1 -L 2 -;

L 1 is absent or —CH 2 —;

X 1 is selected from the group consisting of —SO 2 —, —NR 5 —, —SO 2 NR 5 —, —NR 5 SO 2 —, —C(═O)NR 5 —, and —NR 5 C(═O)—;

each R 5 is independently selected from the group consisting of H, D, substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 deuteroalkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, and substituted or unsubstituted benzyl;

L 2 is absent or substituted or unsubstituted C 1 -C 4 alkylene;

Y is selected from the group consisting of D, substituted or unsubstituted C 1 -C 6 deuteroalkyl, substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, substituted or unsubstituted naphthyl, and substituted or unsubstituted heteroaryl, wherein if Y is substituted then Y is substituted with 1-4 R 7 groups;

each R 7 is independently selected from the group consisting of D, —CN, F, Cl, Br, I, —OH, —OR 9 , —SR 9 , —S(═O)R 9 , —S(═O) 2 R 9 , —N(R 8 )S(═O) 2 R 9 , —S(═O) 2 NH 2 , —S(═O) 2 NR 8 R 9 , —C(═O)R 9 , —OC(═O)R 9 , —CO 2 R 8 , —OCO 2 R 9 , —NH 2 , —NR 8 R 9 , —C(═O)NH 2 , —C(═O)NR 8 R 9 , —OC(═O)NH 2 , —OC(═O)NR 8 R 9 , —NR 8 C(═O)NH 2 , —NR 8 C(═O)NR 8 R 9 , —NR 8 C(═O)R 9 , —NR 8 C(═O)OR 9 , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted C 1 -C 6 deuteroalkyl, substituted or unsubstituted C 1 -C 6 fluoroalkyl, a substituted or unsubstituted C 3 -C 6 cycloalkyl, a substituted or unsubstituted C 2 -C 6 heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, a substituted or unsubstituted —C 1 -C 4 alkylene-C 3 -C 10 cycloalkyl, a substituted or unsubstituted —C 1 -C 4 alkylene-C 2 -C 10 heterocycloalkyl, a substituted or unsubstituted —C 1 -C 4 alkylene-aryl, and a substituted or unsubstituted —C 1 -C 4 alkylene-heteroaryl;

each R 8 is independently selected from the group consisting of H, C 1 -C 6 alkyl, and C 1 -C 6 fluoroalkyl;

each R 9 is independently selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, a substituted or unsubstituted C 3 -C 6 cycloalkyl, a substituted or unsubstituted C 2 -C 6 heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted —C 1 -C 4 alkylene-C 3 -C 10 cycloalkyl, a substituted or unsubstituted —C 1 -C 4 alkylene-C 2 -C 10 heterocycloalkyl, a substituted or unsubstituted —C 1 -C 4 alkylene-aryl, and a substituted or unsubstituted —C 1 -C 4 alkylene-heteroaryl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:

the groups

and —X—Y are in a 1,4-relationship on the phenyl or a 1,3-relationship on the phenyl.

3. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:

X is absent or -L 1 -X 1 -L 2 -;

L 1 is absent or —CH 2 —;

X 1 is selected from the group consisting of —SO 2 —, —NR 5 —, —SO 2 NR 5 —, —NR 5 SO 2 —, —C(═O)NR 5 —, or —NR 5 C(═O)—;

each R 5 is independently selected from the group consisting of H, C 1 -C 4 alkyl, and substituted or unsubstituted benzyl;

L 2 is absent or —CH 2 —;

Y is selected from the group consisting of substituted or unsubstituted C 1 -C 6 deuteroalkyl, substituted or unsubstituted C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, substituted or unsubstituted naphthyl, and substituted or unsubstituted heteroaryl, wherein if Y is substituted then Y is substituted with 1-2 R 7 groups.

4. The compound of claim 1 , wherein the compound of Formula (Ia) has the structure of Formula (IIa), or a pharmaceutically acceptable salt, or solvate thereof, wherein:

5. The compound of claim 1 , wherein the compound of Formula (Ia) has the structure of Formula (IIIa), or a pharmaceutically acceptable salt, or solvate thereof, wherein:

6. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:

L 1 is absent;

R 5 is independently selected from the group consisting of H, C 1 -C 4 alkyl, and substituted or unsubstituted benzyl; and

L 2 is absent or —CH 2 —.

7. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:

Y is selected from the group consisting of substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted C 2 -C 6 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, or substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted bicyclic heteroaryl, wherein if Y is substituted then Y is substituted with 1-2 R 7 groups.

8. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:

Y is a substituted or unsubstituted phenyl, wherein if Y is substituted then Y is substituted with 1-2 R 7 groups.

9. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:

Y is selected from the group consisting of substituted or unsubstituted cyclopropyl, substituted or unsubstituted cyclobutyl, substituted or unsubstituted cyclopentyl, and substituted or unsubstituted cyclohexyl, wherein if Y is substituted then Y is substituted with 1-2 R 7 groups.

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

Y is a substituted or unsubstituted monocyclic 6-membered heteroaryl containing 1-2 N atoms, wherein if Y is substituted then Y is substituted with 1-2 R 7 groups;

or Y is a substituted or unsubstituted monocyclic 5-membered C 1 -C 4 heteroaryl containing 1-4 N atoms and 0 or 1 S or O atom, or a substituted or unsubstituted monocyclic 5-membered C 1 -C 4 heteroaryl containing 0-4 N atoms and 1 S or O atom, wherein if Y is substituted then Y is substituted with 1-2 R 7 groups.

11. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:

Y is selected from the group consisting of substituted or unsubstituted furanyl, substituted or unsubstituted thienyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted pyrazolyl, substituted or unsubstituted triazolyl, substituted or unsubstituted tetrazolyl, substituted or unsubstituted isoxazolyl, substituted or unsubstituted isothiazolyl, substituted or unsubstituted oxadiazolyl, substituted or unsubstituted thiadiazolyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyrazinyl, substituted or unsubstituted pyridazinyl, and substituted or unsubstituted triazinyl, wherein if Y is substituted then Y is substituted with 1-2 R 7 groups;

or Y is selected from the group consisting of substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted tetrahydrofuranyl, substituted or unsubstituted dihydrofuranyl, substituted or unsubstituted tetrahydrothienyl, substituted or unsubstituted oxazolidinonyl, substituted or unsubstituted tetrahydropyranyl, substituted or unsubstituted dihydropyranyl, substituted or unsubstituted tetrahydrothiopyranyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted morpholinyl, substituted or unsubstituted thiomorpholinyl, substituted or unsubstituted thioxanyl, substituted or unsubstituted piperazinyl, substituted or unsubstituted aziridinyl, substituted or unsubstituted azetidinyl, substituted or unsubstituted oxetanyl, substituted or unsubstituted thietanyl, substituted or unsubstituted homopiperidinyl, substituted or unsubstituted oxepanyl, substituted or unsubstituted thiepanyl, substituted or unsubstituted oxazepinyl, substituted or unsubstituted diazepinyl, substituted or unsubstituted thiazepinyl, and substituted or unsubstituted 1,2,3,6-tetrahydropyridinyl, wherein if Y is substituted then Y is substituted with 1-2 R 7 groups;

or Y is selected from the group consisting of substituted or unsubstituted indolizinyl, substituted or unsubstituted indolyl, substituted or unsubstituted benzofuranyl, substituted or unsubstituted benzothiophenyl, substituted or unsubstituted indazolyl, substituted or unsubstituted benzimidazolyl, substituted or unsubstituted purinyl, substituted or unsubstituted quinolizinyl, substituted or unsubstituted quinolinyl, substituted or unsubstituted isoquinolinyl, substituted or unsubstituted cinnolinyl, substituted or unsubstituted phthalazinyl, substituted or unsubstituted quinazolinyl, substituted or unsubstituted quinoxalinyl, substituted or unsubstituted 1,8-naphthyridinyl, and substituted or unsubstituted pteridinyl wherein if Y is substituted then Y is substituted with 1-2 R 7 groups.

12. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:

L 1 is absent or —CH 2 —;

X 1 is selected from the group consisting of —NR 5 —, —SO 2 NR 5 —, and —C(═O)NR 5 —;

R 5 is independently selected from the group consisting of H, D, C 1 -C 4 alkyl, and substituted or unsubstituted benzyl; and

L 2 is absent.

13. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:

each R 7 is independently selected from the group consisting of D, —CN, F, Cl, Br, I, —OH, —OR 9 , —SR 9 , —S(═O)R 9 , —S(═O) 2 R 9 , —N(R 8 )S(═O) 2 R 9 , —S(═O) 2 NH 2 , —S(═O) 2 NR 8 R 9 , —C(═O)R 9 , —OC(═O)R 9 , —CO 2 R 8 , —OCO 2 R 9 , —NH 2 , —NR 8 R 9 , —C(═O)NH 2 , —C(═O)NR 8 R 9 , —OC(═O)NH 2 , —OC(═O)NR 8 R 9 , —NR 8 C(═O)NH 2 , —NR 8 C(═O)NR 8 R 9 , —NR 8 C(═O)R 9 , —NR 8 C(═O)OR 9 , C 1 -C 6 alkyl, C 1 -C 6 deuteroalkyl, C 1 -C 6 fluoroalkyl, a unsubstituted C 3 -C 6 cycloalkyl, a unsubstituted C 2 -C 6 heterocycloalkyl, a unsubstituted phenyl, or a unsubstituted heteroaryl, a unsubstituted —CH 2 —C 3 -C 6 cycloalkyl, a unsubstituted —CH 2 —C 2 -C 6 heterocycloalkyl, a unsubstituted —CH 2 -phenyl, and a unsubstituted —CH 2 -heteroaryl;

each R 8 is independently selected from the group consisting of H, C 1 -C 6 alkyl, and C 1 -C 6 fluoroalkyl;

each R 9 is independently selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 6 fluoroalkyl, a substituted or unsubstituted C 3 -C 6 cycloalkyl, a unsubstituted C 2 -C 6 heterocycloalkyl, a unsubstituted phenyl, a unsubstituted heteroaryl, a unsubstituted —CH 2 —C 3 -C 10 cycloalkyl, a unsubstituted —CH 2 —C 2 -C 10 heterocycloalkyl, a unsubstituted —CH 2 -phenyl, and a unsubstituted —CH 2 -heteroaryl.

14. A compound that is:

Ethyl 4-(3-((1H-pyrazol-4-yl)methyl)ureido)benzoate;

N-(3-Chloro-phenyl)-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzamide;

4-(3-((1H-pyrazol-4-yl)methyl)ureido)-N-(2-methoxyphenyl)benzamide;

4-(3-((1H-pyrazol-4-yl)methyl)ureido)-N-(2-chlorophenyl)benzamide;

4-(3-((1H-pyrazol-4-yl)methyl)ureido)-N-(4-methoxyphenyl)benzamide;

4-(3-((1H-pyrazol-4-yl)methyl)ureido)-N-(4-chlorophenyl)benzamide;

4-(3-((1H-pyrazol-4-yl)methyl)ureido)-N-(3-methoxyphenyl)benzamide;

4-[3-(1H-Pyrazol-4-ylmethyl)-ureido]-N-pyridin-2-yl-benzenesulfonamide;

N-Benzyl-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

1-[4-(3,4-Dihydro-1H-isoquinoline-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(8-Oxa-3-aza-bicyclo[3.2.1]octane-3-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

N-Cyclobutylmethyl-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

N-Phenyl-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

N-Cyclopentyl-N-methyl-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

N-Benzyl-N-isopropyl-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

N-(3-Methoxy-benzyl)-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

N-(2-Chloro-benzyl)-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

N-(2-Methoxy-benzyl)-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

N-(4-Methoxy-benzyl)-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

N-(4-Chloro-benzyl)-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

1-[4-(3-Chloro-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(2-Chloro-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(4-Chloro-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(2-Methoxy-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(3-Methoxy-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-(4-Benzenesulfonyl-phenyl)-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(4-Methoxy-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

N-{4-[3-(1H-Pyrazol-4-ylmethyl)-ureido]-phenyl}-benzenesulfonamide;

N-(4-(3-((1H-pyrazol-4-yl)methyl)ureido)phenyl)-1-phenylmethanesulfonamide;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((4-(trifluoromethyl)phenyl)sulfonyl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(pyridin-2-ylsulfonyl)phenyl)urea;

1-[4-(5-Methyl-pyridine-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((2-fluorophenyl)sulfonyl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((3-fluorophenyl)sulfonyl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((4-fluorophenyl)sulfonyl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((3-(trifluoromethyl)phenyl)sulfonyl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(pyridin-4-ylsulfonyl)phenyl)urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(4-trifluoromethoxy-benzenesulfonyl)-phenyl]-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(toluene-4-sulfonyl)-phenyl]-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(toluene-3-sulfonyl)-phenyl]-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(toluene-2-sulfonyl)-phenyl]-urea;

1-[4-(4-Cyano-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(3,4-Dichloro-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(5-Chloro-pyridine-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(2-trifluoromethyl-benzenesulfonyl)-phenyl]-urea;

N-(3-Fluoro-benzyl)-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

1-[4-(6-Methyl-pyridine-3-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(pyrimidin-5-ylsulfonyl)phenyl)urea;

1-(4-Cyclohexanesulfonyl-phenyl)-3-(1H-pyrazol-4-ylmethyl)-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(2-trifluoromethoxy-benzenesulfonyl)-phenyl]-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(3-trifluoromethoxy-benzenesulfonyl)-phenyl]-urea;

1-[4-(3,4-Difluoro-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(thiazole-2-sulfonyl)-phenyl]-urea;

1-[4-(3,4-Dichloro-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

N-(4-Methyl-benzyl)-4-[3-(1H-pyrazol-4-ylmethyl)-ureido]-benzenesulfonamide;

1-[4-(2,4-Dichloro-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(pyridine-3-sulfonyl)-phenyl]-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(thiazole-2-sulfonyl)-phenyl]-urea;

1-[4-(3,5-Difluoro-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

of 1-[4-(1-Isopropyl-1H-pyrazole-4-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(Pyrazine-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(1-Methyl-piperidine-4-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(1-Isopropyl-piperidine-4-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(1-Isobutyl-piperidine-4-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

of 1-[4-(2,4-Difluoro-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(6-Methyl-pyridine-3-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(1-Methyl-1H-pyrazole-4-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(pyrimidine-2-sulfonyl)-phenyl]-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-{4-[1-(tetrahydro-pyran-4-yl)-piperidine-4-sulfonyl]-phenyl}-urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(benzo[d]thiazol-2-yl)phenyl)urea;

1-[4-(1H-Indazol-3-yl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(1-Methyl-1H-indazol-3-yl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((4-phenylthiazol-2-yl)amino)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(5-benzylthiazol-2-yl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((1H-pyrazol-4-yl)sulfonyl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(benzo[d]thiazol-2-ylamino)phenyl)urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(4-o-tolyl-thiazol-2-ylamino)-phenyl]-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(4-m-tolyl-thiazol-2-ylamino)-phenyl]-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(4-p-tolyl-thiazol-2-ylamino)-phenyl]-urea;

1-{4-[4-(2-Fluoro-phenyl)-thiazol-2-ylamino]-phenyl}-3-(1H-pyrazol-4-ylmethyl)-urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(1,5-dimethyl-1H-indazol-3-yl)phenyl)urea;

1-[4-(1,6-Dimethyl-1H-indazol-3-yl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-{4-[4-(3-Fluoro-phenyl)-thiazol-2-ylamino]-phenyl}-3-(1H-pyrazol-4-ylmethyl)-urea;

1-{4-[4-(4-Fluoro-phenyl)-thiazol-2-ylamino]-phenyl}-3-(1H-pyrazol-4-ylmethyl)-urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((4-(2-methoxyphenyl)thiazol-2-yl)amino)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((4-(3-methoxyphenyl)thiazol-2-yl)amino)phenyl)urea;

1-(4-Benzothiazol-4-yl-phenyl)-3-(1H-pyrazol-4-ylmethyl)-urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(1,7-dimethyl-1H-indazol-3-yl)phenyl)urea;

1-[4-(5-Methoxy-1-methyl-1H-indazol-3-yl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(5-Fluoro-1-methyl-1H-indazol-3-yl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-{4-[4-(2-Chloro-phenyl)-thiazol-2-ylamino]-phenyl}-3-(1H-pyrazol-4-ylmethyl)-urea;

1-{4-[4-(3-Chloro-phenyl)-thiazol-2-ylamino]-phenyl}-3-(1H-pyrazol-4-ylmethyl)-urea;

1-{4-[4-(4-Chloro-phenyl)-thiazol-2-ylamino]-phenyl}-3-(1H-pyrazol-4-ylmethyl)-urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((4-(4-methoxyphenyl)thiazol-2-yl)amino)phenyl)urea;

1-[4-(1H-Benzoimidazol-4-yl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-((1H-Pyrazol-4-yl) methyl)-3-(4-([1,1′-biphenyl]-3-ylsulfonyl)phenyl)urea;

1-((1H-Pyrazol-4-yl) methyl)-3-(4-([1,1′-biphenyl]-2-ylsulfonyl)phenyl)urea;

1-[4-(1-Methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(5-chloro-1-methyl-1H-indazol-3-yl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((5-phenylthiazol-2-yl)amino)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(5-phenylthiazol-2-yl)phenyl)urea;

1-[4-(1-Methyl-1H-pyrazolo[4,3-b]pyridin-3-yl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(1-methyl-1H-pyrazolo[3,4-c]pyridin-3-yl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-(1,4-dimethyl-1H-indazol-3-yl)phenyl)urea;

1-[4-(1-Methyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(2-pyridin-3-yl-benzenesulfonyl)-phenyl]-urea;

1-[4-(3-Iodo-benzenesulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(2′-Fluoro-biphenyl-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(3′-Fluoro-biphenyl-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(4′-Fluoro-biphenyl-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(2′-Methoxy-biphenyl-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(3′-Methoxy-biphenyl-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-(1H-Pyrazol-4-ylmethyl)-3-[4-(2-pyridin-4-yl-benzenesulfonyl)-phenyl]-urea;

1-[4-(3′-Chloro-biphenyl-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(4′-Methyl-biphenyl-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(3′-Methyl-biphenyl-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-[4-(4′-Methoxy-biphenyl-2-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((2′-chloro-[1,1′-biphenyl]-2-yl)sulfonyl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((4′-cyano-[1,1′-biphenyl]-2-yl)sulfonyl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((2-(6-methoxypyridin-3-yl)phenyl)sulfonyl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((3′-cyano-[1,1′-biphenyl]-2-yl)sulfonyl)phenyl)urea;

1-((1H-Pyrazol-4-yl)methyl)-3-(4-((2′-methyl-[1,1′-biphenyl]-2-yl)sulfonyl)phenyl)urea;

1-[4-(6-Hydroxy-pyridine-3-sulfonyl)-phenyl]-3-(1H-pyrazol-4-ylmethyl)-urea;

or a pharmaceutically acceptable salt, or solvate thereof.

15. A compound that is:

Ethyl 4-(3-(oxazol-5-ylmethyl)ureido)benzoate;

N-Benzyl-N-isopropyl-4-(3-oxazol-5-ylmethyl-ureido)-benzenesulfonamide;

1-[4-(3,4-Dihydro-1H-isoquinoline-2-sulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

N-Benzyl-4-(3-oxazol-5-ylmethyl-ureido)-benzenesulfonamide;

1-(4-Benzenesulfonyl-phenyl)-3-oxazol-5-ylmethyl-urea;

N-[4-(3-Oxazol-5-ylmethyl-ureido)-phenyl]-benzenesulfonamide;

1-Oxazol-5-ylmethyl-3-[4-(4-trifluoromethoxy-benzenesulfonyl)-phenyl]-urea;

1-[4-(4-Cyano-benzenesulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-(3-Chlorophenyl)-N-(4-(3-(oxazol-5-ylmethyl)ureido)phenyl)methanesulfonamide;

1-(4-Chlorophenyl)-N-(4-(3-(oxazol-5-ylmethyl)ureido)phenyl)methanesulfonamide;

1-(3,4-Dichlorophenyl)-N-(4-(3-(oxazol-5-ylmethyl)ureido)phenyl)methanesulfonamide;

1-(2-Chlorophenyl)-N-(4-(3-(oxazol-5-ylmethyl)ureido)phenyl)methanesulfonamide;

1-Oxazol-5-ylmethyl-3-[4-(toluene-4-sulfonyl)-phenyl]-urea;

1-[4-(3,4-Dichloro-benzenesulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-(Oxazol-5-ylmethyl)-3-(4-(pyridin-2-ylsulfonyl)phenyl)urea;

1-(4-((3-Chlorophenyl)sulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-(Oxazol-5-ylmethyl)-3-(4-(pyridin-4-ylsulfonyl)phenyl)urea;

1-(4-((2-Methoxyphenyl)sulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-Oxazol-5-ylmethyl-3-[4-(toluene-3-sulfonyl)-phenyl]-urea;

1-Oxazol-5-ylmethyl-3-[4-(toluene-2-sulfonyl)-phenyl]-urea;

1-[4-(5-Chloro-pyridine-2-sulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-(4-((2-Fluorophenyl)sulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-(4-((3-Fluorophenyl)sulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-(4-((4-Fluorophenyl)sulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-[4-(2-Chloro-benzenesulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-Oxazol-5-ylmethyl-3-[4-(2-trifluoromethyl-benzenesulfonyl)-phenyl]-urea;

1-(Oxazol-5-ylmethyl)-3-(4-((3-(trifluoromethyl)phenyl)sulfonyl)phenyl)urea;

1-(Oxazol-5-ylmethyl)-3-(4-((4-(trifluoromethyl)phenyl)sulfonyl)phenyl)urea;

1-(4-Cyclohexanesulfonyl-phenyl)-3-oxazol-5-ylmethyl-urea;

1-Oxazol-5-ylmethyl-3-[4-(4-trifluoromethoxy-benzenesulfonyl)-phenyl]-urea;

1-[4-(6-Methyl-pyridine-3-sulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-(4-((4-Chlorophenyl)sulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-Oxazol-5-ylmethyl-3-[4-(thiazole-2-sulfonyl)-phenyl]-urea;

1-[4-(1-Methyl-piperidine-4-sulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-Oxazol-5-ylmethyl-3-[4-(3-trifluoromethoxy-benzenesulfonyl)-phenyl]-urea;

1-[4-(3-Methoxy-benzenesulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-[4-(3,4-Difluoro-benzenesulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-Oxazol-5-ylmethyl-3-[4-(thiazole-2-sulfonyl)-phenyl]-urea;

1-[4-(3,4-Dichloro-benzenesulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-Oxazol-5-ylmethyl-3-[4-(pyridine-3-sulfonyl)-phenyl]-urea;

1-[4-(3,5-Difluoro-benzenesulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-[4-(1-Isopropyl-1H-pyrazole-4-sulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-Oxazol-5-ylmethyl-3-[4-(pyrazine-2-sulfonyl)-phenyl]-urea;

1-[4-(2,4-Difluoro-benzenesulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-[4-(6-Methoxy-pyridine-3-sulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-[4-(4-Methoxy-benzenesulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-[4-(1-Methyl-1H-pyrazole-4-sulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-Oxazol-5-ylmethyl-3-[4-(pyrimidine-2-sulfonyl)-phenyl]-urea;

1-Oxazol-5-ylmethyl-3-{4-[1-(tetrahydro-pyran-4-yl)-piperidine-4-sulfonyl]-phenyl}-urea;

1-[4-(1H-Indazol-3-yl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-(4-(Benzo[d]thiazol-2-yl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-[4-(6-Hydroxy-pyridine-3-sulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-[4-(6-Chloro-pyridine-3-sulfonyl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-[4-(1-Methyl-1H-indazol-3-yl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-(Oxazol-5-ylmethyl)-3-(4-((4-phenylthiazol-2-yl)amino)phenyl)urea;

1-(4-(5-Benzylthiazol-2-yl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-(4-((1H-pyrazol-4-yl)sulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-(4-(Benzo[d]thiazol-2-ylamino)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-(4-(1,5-Dimethyl-1H-indazol-3-yl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-[4-(1,6-Dimethyl-1H-indazol-3-yl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-(4-(1,7-Dimethyl-1H-indazol-3-yl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-(4-Benzothiazol-4-yl-phenyl)-3-oxazol-5-ylmethyl-urea;

1-[4-(5-Methoxy-1-methyl-1H-indazol-3-yl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-[4-(5-Fluoro-1-methyl-1H-indazol-3-yl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-[4-(1H-Benzoimidazol-4-yl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-(4-([1,1′-Biphenyl]-3-ylsulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-(4-([1,1′-Biphenyl]-2-ylsulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-[4-(1-Methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-(4-(5-Chloro-1-methyl-1H-indazol-3-yl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-(Oxazol-5-ylmethyl)-3-(4-((5-phenylthiazol-2-yl)amino)phenyl)urea;

1-(Oxazol-5-ylmethyl)-3-(4-(5-phenylthiazol-2-yl)phenyl)urea;

1-[4-(1-Methyl-1H-pyrazolo[4,3-b]pyridin-3-yl)-phenyl]-3-oxazol-5-ylmethyl-urea;

1-(4-(1,7-Dimethyl-1H-indazol-3-yl)phenyl)-3-(oxazol-5-ylmethyl)urea;

1-[4-(1-Methyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-phenyl]-3-oxazol-5-ylmethyl-urea;

or a pharmaceutically acceptable salt, or solvate thereof.

16. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, and at least one pharmaceutically acceptable excipient.

17. A method of treating a disease or condition mediated by nicotinamide phosphoribosyltransferase (NAMPT) activity in a mammal comprising administering a compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, to the mammal.

18. The method of claim 17 , wherein the disease or condition is cancer, a hyperproliferative disease or condition, an inflammatory disease or condition, a metabolic disorder, a neurodegenerative disease or disorder, or a muscle wasting disease.

19. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt, or solvate thereof.

20. The compound of claim 1 , or a pharmaceutically acceptable salt, or solvate thereof, wherein:

X 1 is selected from the group consisting of —SO 2 — and —C(═O)NR 5 —;

R 5 is selected from the group consisting of H, and substituted or unsubstituted C 1 -C 6 alkyl;

L 2 is absent;

Y is selected from the group consisting substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, and substituted or unsubstituted naphthyl, wherein if Y is substituted then Y is substituted with 1-2 R 7 groups; and

each R 7 is independently selected from the group consisting of F, Cl, Br, unsubstituted C 1 -C 6 alkyl, and unsubstituted C 3 -C 6 cycloalkyl.