US 11,806,337 B2
Small molecule activators of nicotinamide phosphoribosyltransferase (NAMPT) and uses thereof
Stephen Gardell, Orlando, FL (US); Anthony B. Pinkerton, Rancho Santa Fe, CA (US); Eduard Sergienko, San Diego, CA (US); and Hampton Sessions, Orlando, FL (US)
Assigned to SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE, La Jolla, CA (US)
Filed by Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (US)
Filed on Jul. 27, 2022, as Appl. No. 17/875,216.
Application 17/875,216 is a continuation of application No. 16/475,635, granted, now 11,452,717, previously published as PCT/US2018/012943, filed on Jan. 9, 2018.
Claims priority of provisional application 62/444,557, filed on Jan. 10, 2017.
Prior Publication US 2023/0116770 A1, Apr. 13, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/4409 (2006.01); A61K 31/196 (2006.01); A61K 31/245 (2006.01); A61K 31/415 (2006.01); A61K 31/4155 (2006.01); A61K 31/417 (2006.01); A61K 31/4192 (2006.01); A61K 31/42 (2006.01); A61K 31/422 (2006.01); A61K 31/426 (2006.01); A61K 31/427 (2006.01); A61K 31/4355 (2006.01); A61K 31/437 (2006.01); A61K 31/44 (2006.01); A61K 31/4402 (2006.01); A61K 31/4406 (2006.01); A61K 31/4418 (2006.01); A61K 31/443 (2006.01); A61K 31/4433 (2006.01); A61K 31/4436 (2006.01); A61K 31/4439 (2006.01); A61K 31/444 (2006.01); A61K 31/454 (2006.01); A61K 31/4545 (2006.01); A61K 31/47 (2006.01); A61K 31/472 (2006.01); A61K 31/4725 (2006.01); A61K 31/497 (2006.01); A61K 31/50 (2006.01); A61K 31/505 (2006.01); A61K 31/5377 (2006.01); A61K 31/5386 (2006.01); C07C 275/42 (2006.01); C07D 213/40 (2006.01); C07D 213/56 (2006.01); C07D 213/643 (2006.01); C07D 213/73 (2006.01); C07D 213/74 (2006.01); C07D 231/12 (2006.01); C07D 233/64 (2006.01); C07D 237/08 (2006.01); C07D 239/26 (2006.01); C07D 249/04 (2006.01); C07D 261/08 (2006.01); C07D 263/32 (2006.01); C07D 277/28 (2006.01); C07D 401/06 (2006.01); C07D 401/12 (2006.01); C07D 403/12 (2006.01); C07D 405/12 (2006.01); C07D 405/14 (2006.01); C07D 409/12 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 417/12 (2006.01); C07D 471/04 (2006.01); C07D 498/08 (2006.01)
CPC A61K 31/4409 (2013.01) [A61K 31/196 (2013.01); A61K 31/245 (2013.01); A61K 31/415 (2013.01); A61K 31/417 (2013.01); A61K 31/4155 (2013.01); A61K 31/4192 (2013.01); A61K 31/42 (2013.01); A61K 31/422 (2013.01); A61K 31/426 (2013.01); A61K 31/427 (2013.01); A61K 31/437 (2013.01); A61K 31/4355 (2013.01); A61K 31/44 (2013.01); A61K 31/4402 (2013.01); A61K 31/443 (2013.01); A61K 31/444 (2013.01); A61K 31/4406 (2013.01); A61K 31/4418 (2013.01); A61K 31/4433 (2013.01); A61K 31/4436 (2013.01); A61K 31/4439 (2013.01); A61K 31/454 (2013.01); A61K 31/4545 (2013.01); A61K 31/47 (2013.01); A61K 31/472 (2013.01); A61K 31/4725 (2013.01); A61K 31/497 (2013.01); A61K 31/50 (2013.01); A61K 31/505 (2013.01); A61K 31/5377 (2013.01); A61K 31/5386 (2013.01); C07C 275/42 (2013.01); C07D 213/40 (2013.01); C07D 213/56 (2013.01); C07D 213/643 (2013.01); C07D 213/73 (2013.01); C07D 213/74 (2013.01); C07D 231/12 (2013.01); C07D 233/64 (2013.01); C07D 237/08 (2013.01); C07D 239/26 (2013.01); C07D 249/04 (2013.01); C07D 261/08 (2013.01); C07D 263/32 (2013.01); C07D 277/28 (2013.01); C07D 401/06 (2013.01); C07D 401/12 (2013.01); C07D 403/12 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 409/12 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 417/12 (2013.01); C07D 471/04 (2013.01); C07D 498/08 (2013.01)] 20 Claims
 
1. A pharmaceutical composition comprising a compound of Formula (Ia), or a pharmaceutically acceptable salt, or solvate thereof:

OG Complex Work Unit Chemistry
wherein:

OG Complex Work Unit Chemistry
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—, —NR5C(═O)—, —OC(═O)—, —C(═O)O—, —OC(═O)O—, —C(═O)—, —OC(═O)NR5—, —NR5C(═O)O—, and —NR5C(═O)NR5—;
each R5 is independently selected from the group consisting of H, D, unsubstituted C1-C6alkyl, unsubstituted C1-C6deuteroalkyl, unsubstituted C1-C6fluoroalkyl, unsubstituted C3-C6cycloalkyl, and unsubstituted benzyl;
L2 is absent or unsubstituted C1-C4alkylene;
Y is selected from the group consisting of D, unsubstituted C1-C6deuteroalkyl, unsubstituted C1-C6fluoroalkyl, 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, unsubstituted C1-C6alkyl, unsubstituted C1-C6deuteroalkyl, unsubstituted C1-C6fluoroalkyl, a substituted or—unsubstituted C3-C6cycloalkyl, a substituted or unsubstituted C2-C6heterocycloalkyl, a substituted or unsubstituted aryl, 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, C1-C6heteroalkyl, 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, and at least one pharmaceutically acceptable excipient.
 
15. A pharmaceutical composition comprising 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;
[[1]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-yl methyl)-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-yl methyl)-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;
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;
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, and at least one pharmaceutically acceptable excipient.
 
16. A pharmaceutical composition comprising 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-ylsutfonyl)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, and at least one pharmaceutically acceptable excipient.