US 11,452,717 B2Granted

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

AssigneeSanford Burnham Prebys Medical Discovery Institute

InventorsStephen Gardell, Anthony B. Pinkerton, Eduard Sergienko, Hampton Sessions

Life of this patent

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Abstract

Provided herein are small molecule activators of Nicotinamide Phosphoribosyltransferase (NAMPT), compositions comprising the compounds, and methods of using the compounds and compositions.

Claims20

Dependent claims

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

wherein:
X is absent or -L1-X1-L2-;
L1 is absent or —CH2—;
X1 is selected from the group consisting of —SO2—, —NR5—, —SO2NR5—, —NR5SO2—, —C(═O)NR5—, and —NR5C(═O)—;
each R5 is independently selected from the group consisting of H, D, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C3-C6cycloalkyl, and substituted or unsubstituted benzyl;
L2 is absent or substituted or unsubstituted C1-C4alkylene;
Y is selected from the group consisting of D, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, 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 R7 groups;
each R7 is independently selected from the group consisting of D, —CN, F, Cl, Br, I, —OH, —OR9, —SR9, —S(═O)R9, —S(═O)2R9, —N(R8)S(═O)2R9, —S(═O)2NH2, —S(═O)2NR8R9, —C(═O)R9, —OC(═O)R9, —CO2R8, —OCO2R9, —NH2, —NR8R9, —C(═O)NH2, —C(═O)NR8R9, —OC(═O)NH2, —OC(═O)NR8R9, —NR8C(═O)NH2, —NR8C(═O)NR8R9, —NR8C(═O)R9, —NR8C(═O)OR9, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, a substituted or unsubstituted C3-C6cycloalkyl, a substituted or unsubstituted C2-C6heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, a substituted or unsubstituted —C1-C4alkylene-C3-C10cycloalkyl, a substituted or unsubstituted —C1-C4alkylene-C2-C10heterocycloalkyl, a substituted or unsubstituted —C1-C4alkylene-aryl, and a substituted or unsubstituted —C1-C4alkylene-heteroaryl;
each R8 is independently selected from the group consisting of H, C1-C6alkyl, and C1-C6fluoroalkyl;
each R9 is independently selected from the group consisting of C1-C6alkyl, C1-C6fluoroalkyl, a substituted or unsubstituted C3-C6cycloalkyl, a substituted or unsubstituted C2-C6heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted —C1-C4alkylene-C3-C10cycloalkyl, a substituted or unsubstituted —C1-C4alkylene-C2-C10heterocycloalkyl, a substituted or unsubstituted —C1-C4alkylene-aryl, and a substituted or unsubstituted —C1-C4alkylene-heteroaryl.

7 more elements

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.

121 more elements

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.

72 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/475,635Filed 9 Jan 2018 · us provisional application
Priority: 10 Jan 2017
Published: US 2021/0161873 A13 Jun 2021
Granted: 27 Sep 2022
Term ends: Not estimatedThe source records don’t support an estimate.

Classification68 codes

A61K 31/4409
Non condensed pyridines; Hydrogenated derivatives thereof: only substituted in position 4, e.g. isoniazid, iproniazid
A61P 25/00
Drugs for disorders of the nervous system
A61K 31/196
Having an amino group: the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
A61K 31/245
Having an amino or nitro group: amino benzoic acid types, e.g. procaine, novocaine

Family

Application62/444,557Us provisional application · filed 10 Jan 2017
US 2021/0161873 A1Pre-grant publication · published 3 Jun 2021
US 11,452,717 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Provided herein are small molecule activators of Nicotinamide Phosphoribosyltransferase (NAMPT), compositions comprising the compounds, and methods of using the compounds and compositions.

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

wherein:
X is absent or -L1-X1-L2-;
L1 is absent or —CH2—;
X1 is selected from the group consisting of —SO2—, —NR5—, —SO2NR5—, —NR5SO2—, —C(═O)NR5—, and —NR5C(═O)—;
each R5 is independently selected from the group consisting of H, D, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C3-C6cycloalkyl, and substituted or unsubstituted benzyl;
L2 is absent or substituted or unsubstituted C1-C4alkylene;
Y is selected from the group consisting of D, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, 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 R7 groups;
each R7 is independently selected from the group consisting of D, —CN, F, Cl, Br, I, —OH, —OR9, —SR9, —S(═O)R9, —S(═O)2R9, —N(R8)S(═O)2R9, —S(═O)2NH2, —S(═O)2NR8R9, —C(═O)R9, —OC(═O)R9, —CO2R8, —OCO2R9, —NH2, —NR8R9, —C(═O)NH2, —C(═O)NR8R9, —OC(═O)NH2, —OC(═O)NR8R9, —NR8C(═O)NH2, —NR8C(═O)NR8R9, —NR8C(═O)R9, —NR8C(═O)OR9, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6deuteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, a substituted or unsubstituted C3-C6cycloalkyl, a substituted or unsubstituted C2-C6heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl, a substituted or unsubstituted —C1-C4alkylene-C3-C10cycloalkyl, a substituted or unsubstituted —C1-C4alkylene-C2-C10heterocycloalkyl, a substituted or unsubstituted —C1-C4alkylene-aryl, and a substituted or unsubstituted —C1-C4alkylene-heteroaryl;
each R8 is independently selected from the group consisting of H, C1-C6alkyl, and C1-C6fluoroalkyl;
each R9 is independently selected from the group consisting of C1-C6alkyl, C1-C6fluoroalkyl, a substituted or unsubstituted C3-C6cycloalkyl, a substituted or unsubstituted C2-C6heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted —C1-C4alkylene-C3-C10cycloalkyl, a substituted or unsubstituted —C1-C4alkylene-C2-C10heterocycloalkyl, a substituted or unsubstituted —C1-C4alkylene-aryl, and a substituted or unsubstituted —C1-C4alkylene-heteroaryl.

7 more elements

Facts

Application

16/475,635Filed 9 Jan 2018 · us provisional application

Priority

10 Jan 2017

Published

US 2021/0161873 A13 Jun 2021

Granted

27 Sep 2022

Term ends

Not estimatedThe source records don’t support an estimate.

Classification68 codes

A61K 31/4409
Non condensed pyridines; Hydrogenated derivatives thereof: only substituted in position 4, e.g. isoniazid, iproniazid
A61P 25/00
Drugs for disorders of the nervous system
A61K 31/196
Having an amino group: the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
A61K 31/245
Having an amino or nitro group: amino benzoic acid types, e.g. procaine, novocaine