Methods for treating spinal muscular atrophy

Abstract

The present invention provides nucleic acid constructs, methods for identifying and validating compounds that increase the inclusion of exon 7 of SMN2 into mRNA transcribed from the SMN2 gene, compounds and pharmaceutical compositions that increase levels of SMN protein produced from the SMN2 gene, and methods for use thereof in treating of SMA.

1 .- 36 . (canceled) 
     
     
         37 . A method for increasing the expression of SMN in a human subject in need thereof, comprising administering to the human subject an effective amount of a compound that increases the inclusion of exon 7 of SMN2 into mRNA transcribed from the SMN2 gene. 
     
     
         38 . A method for treating spinal muscular atrophy (SMA) in a human subject in need thereof, comprising administering to the human subject an effective amount of a compound that increases the inclusion of exon 7 of SMN2 into mRNA transcribed from the SMN2 gene. 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . The method of  claim 37 , wherein the compound is a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable free acid, free base, salt, hydrate, solvate, clathrate, racemate, stereoisomer, or polymorph thereof, wherein: 
         Y and Z are each selected from N or C, wherein Y and Z are each not simultaneously N or C; 
         W is N or C; 
         R 1  is selected from hydrogen or aryl, wherein aryl is optionally substituted with carboxyl and, wherein R 1  is absent when Z is N; 
         R 2  is selected from hydrogen, C 3-14 cycloalkyl, aryl, heteroaryl or heterocyclyl, 
         wherein aryl is optionally substituted with one, two, or three substituents each selected from halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy, C 1-6 alkoxy-carbonyl, amino or C 1-6 alkyl-amino, or one substituent selected from halo-C 1-6 alkyl-amino, hydroxy-C 1-6 alkyl-amino, amino-carbonyl, C 1-6 alkyl-amino-carbonyl, aryl, heteroaryl or heterocyclyl, optionally substituted on heterocyclyl with one or two oxo substituents, 
         wherein heteroaryl is optionally substituted with one or two C 1-6 alkyl substituents or one heterocyclyl substituent, 
         wherein heterocyclyl is optionally substituted with one or two substituents each selected from halogen or C 1-6 alkyl, and 
         wherein R 2  is absent when Y is N; and 
         R 3  is one, two, or three carbon atom substituents each selected from hydrogen, halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, amino, amino-C 1-6 alkyl, C 1-6 alkyl-carbonyl-amino, C 3-14 cycloalkyl, C 3-14 cycloalkyloxy, C 3-14 cycloalkyl-C 1-6 alkyl, aryl, aryloxy, aryloxy-C 1-6 alkyl, heteroaryl, heteroaryl-C 1-6 alkyl, heterocyclyl, heterocyclyl-C 1-6 alkyl or heterocyclyl-carbonyl, 
         wherein each instance of amino is optionally substituted with one or two substituents each selected from C 1-6 alkyl, hydroxy-C 1-6 alkyl, carboxy-C 1-6 alkyl, aryl-C 1-6 alkyl, heterocyclyl-C 1-6 alkyl or aryl optionally substituted with one or two C 1-6 alkyl substituents, 
         wherein each instance of aryl is optionally substituted with one or two substituents each selected from halogen, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy or aryl optionally substituted with one or two C 1-6 alkyl substituents, and 
         wherein each instance of heterocyclyl is optionally substituted with one or two substituents each selected from C 1-6 alkyl or aryl optionally substituted with one or two C 1-6 alkyl substituents, or is optionally substituted on one or two carbon atoms with an oxo substituent. 
       
     
     
         42 . The method of  claim 41 , wherein
 R 2  is selected from hydrogen, aryl, heteroaryl or heterocyclyl,   wherein aryl is optionally substituted with one or two substituents each selected from halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy or C 1-6 alkoxy-carbonyl, or one substituent selected from halo-C 1-6 alkyl-amino, hydroxy-C 1-6 alkyl-amino, amino-carbonyl, aryl, heteroaryl or heterocyclyl optionally substituted with one oxo substituent,   wherein heteroaryl is optionally substituted with one or two C 1-6 alkyl substituents or one heterocyclyl substituent,   wherein heterocyclyl is optionally substituted with two halogen substituents, and wherein R 2  is absent when Y is N; and   R 3  is one, two, or three carbon atom substituents each selected from hydrogen, halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, amino, amino-C 1-6 alkyl, C 1-6 alkyl-carbonyl-amino, aryl, aryloxy, aryloxy-C 1-6 alkyl, heteroaryl, heteroaryl-C 1-6 alkyl, heterocyclyl or heterocyclyl-carbonyl,   wherein each instance of amino is optionally substituted with one or two substituents each selected from C 1-6 alkyl, hydroxy-C 1-6 alkyl, carboxy-C 1-6 alkyl, aryl-C 1-6 alkyl, heterocyclyl-C 1-6 alkyl or aryl optionally substituted with one or two C 1-6 alkyl substituents,   wherein each instance of aryl is optionally substituted with one or two substituents each selected from halogen, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkoxy or halo-C 1-6 alkoxy, and   wherein each instance of heterocyclyl is optionally substituted with one or two C 1-6 alkyl substituents, or is optionally substituted on a carbon atom with an oxo substituent.   
     
     
         43 . The method of  claim 41 , wherein
 R 1  is selected from hydrogen or phenyl, wherein phenyl is optionally substituted with carboxyl and, wherein R 1  is absent when Z is N;   R 2  is selected from hydrogen, phenyl, furanyl, thienyl, pyridinyl, 2,3-dihydro-benzofuranyl or benzo[1,3]dioxolyl,   wherein phenyl is optionally substituted with one or two substituents each selected from halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy or C 1-6 alkoxy-carbonyl, or one substituent selected from halo-C 1-6 alkyl-amino, hydroxy-C 1-6 alkyl-amino, amino-carbonyl, phenyl, pyrazolyl, azetidinyl, pyrrolidinyl or morpholinyl, optionally substituted on pyrrolidinyl with one oxo substituent,   wherein furanyl, thienyl and pyridinyl is optionally substituted with one or two C 1-6 alkyl substituents or one azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl substituent,   wherein benzo[1,3]dioxolyl is optionally substituted with two halogen substituents, and   wherein R 2  is absent when Y is N; and   R 3  is one, two, or three carbon atom substituents each selected from hydrogen, halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, amino, amino-C 1-6 alkyl, C 1-6 alkyl-carbonyl-amino, phenyl, phenyloxy, phenyloxy-C 1-6 alkyl, imidazolyl, pyrazolyl, 1H-1,2,4-triazolyl, benzofuranyl, imidazolyl-C 1-6 alkyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 1,4-diazepanyl, 2,3-dihydro-indolyl, 3,4-dihydroisoquinolin-(1H)-yl, 1,4-dioxa-8-azaspiro[4.5]decanyl, pyrrolidinyl-carbonyl or morpholinyl-carbonyl,   wherein each instance of amino is optionally substituted with one or two substituents each selected from C 1-6  alkyl, hydroxy-C 1-6  alkyl, carboxy-C 1-6  alkyl, phenyl-C 1-6 alkyl, benzo[1,3]dioxolyl-C 1-6 alkyl, or phenyl optionally substituted with one or two C 1-6 alkyl substituents,   wherein each instance of phenyl is optionally substituted with one or two substituents each selected from halogen, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkoxy or halo-C 1-6 alkoxy, and   wherein each instance of azetidinyl, pyrrolidinyl, piperazinyl, morpholinyl or 1,4-diazepanyl is optionally substituted with one or two C 1-6 alkyl substituents, or is optionally substituted on one azetidinyl or pyrrolidinyl carbon atom with an oxo substituent.   
     
     
         44 . The method of  claim 41 , wherein the compound of Formula (I) or a form thereof is a compound of Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), Formula (Ie) or Formula (If) or a form thereof, wherein all substituent variables are as previously defined: 
       
         
           
           
               
               
           
         
       
     
     
         45 . (canceled) 
     
     
         46 . (canceled) 
     
     
         47 . The method of  claim 37 , wherein the compound is:
 3-benzooxazol-2-yl-benzoic acid,   3-(6-methyl-benzooxazol-2-yl)-benzoic acid,   3-(5-phenyl-benzooxazol-2-yl)-benzoic acid,   3-[5-(4-isopropyl-3-methyl-phenoxymethyl)-benzooxazol-2-yl]-benzoic acid,   3-{5-[(4-isopropyl-phenylamino)-methyl]-benzooxazol-2-yl}-benzoic acid,   3-(5-tert-butyl-benzooxazol-2-yl)-benzoic acid,   3-(5-chloro-benzooxazol-2-yl)-benzoic acid,   3-(6-imidazol-1-ylmethyl-benzooxazol-2-yl)-benzoic acid,   3-(5-bromo-benzooxazol-2-yl)-benzoic acid,   4-(5-phenyl-benzooxazol-2-yl)-benzoic acid,   4-(6-methyl-benzooxazol-2-yl)-benzoic acid,   4-(5-chloro-benzooxazol-2-yl)-benzoic acid,   4-(5-tert-butyl-benzooxazol-2-yl)-benzoic acid,   2-(3-carboxy-phenyl)-benzooxazole-6-carboxylic acid,   2-(3-carboxy-phenyl)-benzooxazole-5-carboxylic acid,   3-[5-(morpholine-4-carbonyl)-benzooxazol-2-yl]-benzoic acid,   3-[6-(morpholine-4-carbonyl)-benzooxazol-2-yl]-benzoic acid,   2-biphenyl-4-yl-benzooxazole-6-carboxylic acid,   2-biphenyl-4-yl-benzooxazole-5-carboxylic acid,   4-(5-bromo-benzooxazol-2-yl)-benzoic acid,   3-(5-methyl-benzooxazol-2-yl)-benzoic acid,   3-[5-(1,1-dimethyl-propyl)-benzooxazol-2-yl]-benzoic acid,   3-(6-Phenyl-benzooxazol-2-yl)-benzoic acid,   2-(4-isopropyl-phenyl)-benzooxazole-5-carboxylic acid,   2-(4-isopropyl-phenyl)-benzooxazole-6-carboxylic acid,   2-benzo[1,3]dioxol-5-yl-benzooxazole-5-carboxylic acid,   2-biphenyl-4-yl-benzooxazole-7-carboxylic acid,   2-[4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzooxazole-5-carboxylic acid,   3-[5-(4-trifluoromethoxy-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-[5-(3,4-difluoro-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-(5-benzofuran-2-yl-benzooxazol-2-yl)-benzoic acid,   3-(5-methoxy-benzooxazol-2-yl)-benzoic acid,   3-(6-fluoro-benzooxazol-2-yl)-benzoic acid,   3-[6-(2,6-dimethyl-morpholin-4-yl)-benzooxazol-2-yl]-benzoic acid methyl ester,   2-(4-bromo-phenyl)-benzooxazole-5-carboxylic acid,   3-[5-(4-isopropyl-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-[5-(3,5-dimethyl-phenyl)-benzooxazol-2-yl]-benzoic acid,   2-p-tolyl-benzooxazole-5-carboxylic acid,   2-(4-methoxy-phenyl)-benzooxazole-5-carboxylic acid,   2-(4-pyrrolidin-1-yl-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-piperidin-1-yl-benzooxazol-2-yl)-benzoic acid,   3-(6-morpholin-4-yl-benzooxazol-2-yl)-benzoic acid,   3-(5-pyrrolidin-1-yl-benzooxazol-2-yl)-benzoic acid,   3-(6-pyrazol-1-yl-benzooxazol-2-yl)-benzoic acid,   3-[6-(2-oxo-azetidin-1-yl)-benzooxazol-2-yl]-benzoic acid,   3-[6-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-benzooxazol-2-yl]-benzoic acid,   2-[4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzooxazole-5-carboxylic acid,   3-[6-(4-methyl-piperazin-1-yl)-benzooxazol-2-yl]-benzoic acid,   3-(6-imidazol-1-yl-benzooxazol-2-yl)-benzoic acid,   3-[6-(2,3-dihydro-indol-1-yl)-benzooxazol-2-yl]-benzoic acid,   2-(4-morpholin-4-yl-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-azetidin-1-yl-benzooxazol-2-yl)-benzoic acid,   3-(6-pyrrolidin-1-yl-benzooxazol-2-yl)-benzoic acid,   2-[4-(3-chloro-propylamino)-phenyl]-benzooxazole-5-carboxylic acid,   2-(4-fluoro-phenyl)-benzooxazole-5-carboxylic acid,   2-(4-pyrazol-1-yl-phenyl)-benzooxazole-5-carboxylic acid,   2-(4-azetidin-1-yl-phenyl)-benzooxazole-5-carboxylic acid,   2-phenyl-oxazolo[4,5-b]pyridine,   6-bromo-2-phenyl-oxazolo[4,5-b]pyridine,   3-(6-[1,2,4]triazol-1-yl-benzooxazol-2-yl)-benzoic acid,   3-[6-(2-hydroxy-ethylamino)-benzooxazol-2-yl]-benzoic acid,   3-[5-(2-oxo-pyrrolidin-1-yl)-benzooxazol-2-yl]-benzoic acid,   2-[4-(3-hydroxy-propylamino)-phenyl]-benzooxazole-5-carboxylic acid,   2-phenyl-benzooxazole-6-carboxylic acid,   2-furan-2-yl-benzooxazole-6-carboxylic acid,   2-(2-fluoro-phenyl)-benzooxazole-6-carboxylic acid,   2-(2,5-dimethyl-furan-3-yl)-benzooxazole-6-carboxylic acid,   2-pyridin-4-yl-benzooxazole-6-carboxylic acid,   2-pyridin-3-yl-benzooxazole-6-carboxylic acid,   2-(3-methyl-thiophen-2-yl)-benzooxazole-6-carboxylic acid,   3-[6-(pyrrolidine-1-carbonyl)-benzooxazol-2-yl]-benzoic acid,   3-[6-(5-hydroxy-pentylamino)-benzooxazol-2-yl]-benzoic acid,   3-(6-phenethylamino-benzooxazol-2-yl)-benzamide,   3-[6-(3-phenyl-propylamino)-benzooxazol-2-yl]-benzoic acid,   2-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-benzooxazole-6-carboxylic acid,   3-oxazolo[4,5-b]pyridin-2-yl-benzoic acid,   2-(2,5-dimethyl-furan-3-yl)-benzooxazole-5-carboxylic acid,   2-furan-2-yl-benzooxazole-5-carboxylic acid,   2-benzo[1,3]dioxol-5-yl-benzooxazole-6-carboxylic acid,   3-[6-(6-hydroxy-hexylamino)-benzooxazol-2-yl]-benzoic acid,   3-[6-(4-methyl-[1,4]diazepan-1-yl)-benzooxazol-2-yl]-benzoic acid,   3-(6-phenoxy-benzooxazol-2-yl)-benzoic acid,   3-[6-(4-hydroxy-butylamino)-benzooxazol-2-yl]-benzoic acid,   3-(6-phenethylamino-benzooxazol-2-yl)-benzoic acid,   2-(2-pyrrolidin-1-yl-pyridin-3-yl)-benzooxazole-6-carboxylic acid,   2-(3,4-dimethoxy-phenyl)-benzooxazole-6-carboxylic acid,   2-(6-morpholin-4-yl-pyridin-3-yl)-benzooxazole-6-carboxylic acid,   2-(3,4-dimethoxy-phenyl)-benzooxazole-5-carboxylic acid,   2-(6-pyrrolidin-1-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid,   2-(6-morpholin-4-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid,   2-(3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-5′-yl)-benzooxazole-5-carboxylic acid,   2-(6-azetidin-1-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid,   2-(6-azetidin-1-yl-pyridin-3-yl)-benzooxazole-6-carboxylic acid,   2-(3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-5′-yl)-benzooxazole-6-carboxylic acid,   2-(2,3-dihydro-benzofuran-5-yl)-benzooxazole-6-carboxylic acid,   2-(6-piperazin-1-yl-pyridin-3-yl)-benzooxazole-6-carboxylic acid,   2-(2,3-dihydro-benzofuran-5-yl)-benzooxazole-5-carboxylic acid,   2-(4-trifluoromethoxy-phenyl)-benzooxazole-6-carboxylic acid,   2-(3-methoxy-phenyl)-benzooxazole-6-carboxylic acid,   2-(4-trifluoromethoxy-phenyl)-benzooxazole-5-carboxylic acid,   2-(3-methoxy-phenyl)-benzooxazole-5-carboxylic acid,   3-[6-(benzyl-methyl-amino)-benzooxazol-2-yl]-benzoic acid,   3-{6-[(benzo[1,3]dioxol-5-ylmethyl)-amino]-benzooxazol-2-yl}-benzoic acid,   2-(3-trifluoromethoxy-phenyl)-benzooxazole-6-carboxylic acid,   2-(3-trifluoromethoxy-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-phenylamino-benzooxazol-2-yl)-benzamide,   3-(6-phenoxy-benzooxazol-2-yl)-benzamide,   3-(6-fluoro-benzooxazol-2-yl)-benzamide,   3-(6-morpholin-4-yl-benzooxazol-2-yl)-benzamide,   3-(6-piperidin-1-yl-benzooxazol-2-yl)-benzamide,   3-(6-methoxy-benzooxazol-2-yl)-benzamide,   3-(6-methyl-benzooxazol-2-yl)-benzamide,   4-(6-methyl-benzooxazol-2-yl)-benzamide,   3-(6-phenethylamino-benzooxazol-2-yl)-benzamide,   4-(5-isopropyl-benzo[d]isoxazol-3-yl)-benzoic acid,   3-(5-isopropyl-benzo[d]isoxazol-3-yl)-benzoic acid,   3-(5-methoxy-benzo[d]isoxazol-3-yl)-benzoic acid,   4-(6-methoxy-benzo[d]isoxazol-3-yl)-benzoic acid,   3-(6-methoxy-benzo[d]isoxazol-3-yl)-benzoic acid,   3-(6-phenyl-benzo[d]isoxazol-3-yl)-benzoic acid,   4-(6-phenyl-benzo[d]isoxazol-3-yl)-benzoic acid,   3-(6-p-tolyl-benzo[d]isoxazol-3-yl)-benzoic acid,   4-(6-p-tolyl-benzo[d]isoxazol-3-yl)-benzoic acid,   4-[6-(4-fluoro-phenyl)-benzo[d]isoxazol-3-yl]-benzoic acid,   3-[6-(4-fluoro-phenyl)-benzo[d]isoxazol-3-yl]-benzoic acid,   3-[6-(4-trifluoromethoxy-phenyl)-benzo[d]isoxazol-3-yl]-benzoic acid,   3-[6-(4-trifluoromethyl-phenyl)-benzo[d]isoxazol-3-yl]-benzoic acid,   N-[2-(4-bromo-3-methyl-phenyl)-benzooxazol-5-yl]-acetamide,   or a pharmaceutically acceptable free acid, free base, salt, hydrate, solvate, clathrate, racemate, stereoisomer, or polymorph thereof.   
     
     
         48 . The method of  claim 37 , wherein the compound is:
 3-(6-methyl-benzooxazol-2-yl)-benzoic acid,   3-(5-tert-butyl-benzooxazol-2-yl)-benzoic acid,   3-(6-imidazol-1-ylmethyl-benzooxazol-2-yl)-benzoic acid,   4-(6-methyl-benzooxazol-2-yl)-benzoic acid,   2-biphenyl-4-yl-benzooxazole-6-carboxylic acid,   2-biphenyl-4-yl-benzooxazole-5-carboxylic acid,   3-(5-methyl-benzooxazol-2-yl)-benzoic acid,   3-[5-(1,1-dimethyl-propyl)-benzooxazol-2-yl]-benzoic acid,   3-(6-Phenyl-benzooxazol-2-yl)-benzoic acid,   2-(4-isopropyl-phenyl)-benzooxazole-5-carboxylic acid,   2-benzo[1,3]dioxol-5-yl-benzooxazole-5-carboxylic acid,   2-[4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzooxazole-5-carboxylic acid,   3-[5-(4-trifluoromethoxy-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-[5-(3,4-difluoro-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-(5-benzofuran-2-yl-benzooxazol-2-yl)-benzoic acid,   3-(5-methoxy-benzooxazol-2-yl)-benzoic acid,   2-(4-bromo-phenyl)-benzooxazole-5-carboxylic acid,   3-[5-(4-isopropyl-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-[5-(3,5-dimethyl-phenyl)-benzooxazol-2-yl]-benzoic acid,   2-p-tolyl-benzooxazole-5-carboxylic acid,   2-(4-methoxy-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-piperidin-1-yl-benzooxazol-2-yl)-benzoic acid,   3-(6-morpholin-4-yl-benzooxazol-2-yl)-benzoic acid,   3-(5-pyrrolidin-1-yl-benzooxazol-2-yl)-benzoic acid,   3-(6-pyrazol-1-yl-benzooxazol-2-yl)-benzoic acid,   3-[6-(4-methyl-piperazin-1-yl)-benzooxazol-2-yl]-benzoic acid,   2-(4-morpholin-4-yl-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-azetidin-1-yl-benzooxazol-2-yl)-benzoic acid,   2-[4-(3-chloro-propylamino)-phenyl]-benzooxazole-5-carboxylic acid,   2-(4-fluoro-phenyl)-benzooxazole-5-carboxylic acid,   2-(4-azetidin-1-yl-phenyl)-benzooxazole-5-carboxylic acid,   2-furan-2-yl-benzooxazole-6-carboxylic acid,   2-(2-fluoro-phenyl)-benzooxazole-6-carboxylic acid,   2-(2,5-dimethyl-furan-3-yl)-benzooxazole-6-carboxylic acid,   2-pyridin-3-yl-benzooxazole-6-carboxylic acid,   3-[6-(pyrrolidine-1-carbonyl)-benzooxazol-2-yl]-benzoic acid,   3-(6-phenethylamino-benzooxazol-2-yl)-benzamide,   2-(2,5-dimethyl-furan-3-yl)-benzooxazole-5-carboxylic acid,   3-[6-(4-methyl-[1,4]diazepan-1-yl)-benzooxazol-2-yl]-benzoic acid,   3-(6-phenoxy-benzooxazol-2-yl)-benzoic acid,   2-(6-pyrrolidin-1-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid,   2-(6-morpholin-4-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid,   2-(3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-5′-yl)-benzooxazole-5-carboxylic acid,   2-(6-azetidin-1-yl-pyridin-3-yl)-benzooxazole-6-carboxylic acid,   2-(4-trifluoromethoxy-phenyl)-benzooxazole-5-carboxylic acid,   3-[6-(benzyl-methyl-amino)-benzooxazol-2-yl]-benzoic acid,   2-(3-trifluoromethoxy-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-phenylamino-benzooxazol-2-yl)-benzamide,   3-(6-piperidin-1-yl-benzooxazol-2-yl)-benzamide,   3-(6-methoxy-benzooxazol-2-yl)-benzamide,   3-(6-methyl-benzooxazol-2-yl)-benzamide,   N-[2-(4-bromo-3-methyl-phenyl)-benzooxazol-5-yl]-acetamide,   or a pharmaceutically acceptable free acid, free base, salt, hydrate, solvate, clathrate, racemate, stereoisomer, or polymorph thereof.   
     
     
         49 . The method of  claim 37 , wherein the compound is:
 2-(4-isopropyl-phenyl)-benzooxazole-5-carboxylic acid,   3-(5-methoxy-benzooxazol-2-yl)-benzoic acid,   2-p-tolyl-benzooxazole-5-carboxylic acid,   3-(6-piperidin-1-yl-benzooxazol-2-yl)-benzoic acid,   2-(2-fluoro-phenyl)-benzooxazole-6-carboxylic acid,   2-(6-pyrrolidin-1-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid, or   N-[2-(4-bromo-3-methyl-phenyl)-benzooxazol-5-yl]-acetamide.   
     
     
         50 . The method of  claim 37 , wherein the compound is N-[2-(4-bromo-3-methyl-phenyl)-benzooxazol-5-yl]-acetamide. 
     
     
         51 . The method of  claim 38 , wherein the compound is a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable free acid, free base, salt, hydrate, solvate, clathrate, racemate, stereoisomer, or polymorph thereof, wherein: 
         Y and Z are each selected from N or C, wherein Y and Z are each not simultaneously N or C; 
         W is N or C; 
         R 1  is selected from hydrogen or aryl, wherein aryl is optionally substituted with carboxyl and, wherein R 1  is absent when Z is N; 
         R 2  is selected from hydrogen, C 3-14 cycloalkyl, aryl, heteroaryl or heterocyclyl, 
         wherein aryl is optionally substituted with one, two, or three substituents each selected from halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy, C 1-6 alkoxy-carbonyl, amino or C 1-6 alkyl-amino, or one substituent selected from halo-C 1-6 alkyl-amino, hydroxy-C 1-6 alkyl-amino, amino-carbonyl, C 1-6 alkyl-amino-carbonyl, aryl, heteroaryl or heterocyclyl, optionally substituted on heterocyclyl with one or two oxo substituents, 
         wherein heteroaryl is optionally substituted with one or two C 1-6 alkyl substituents or one heterocyclyl substituent, 
         wherein heterocyclyl is optionally substituted with one or two substituents each selected from halogen or C 1-6 alkyl, and 
         wherein R 2  is absent when Y is N; and 
         R 3  is one, two, or three carbon atom substituents each selected from hydrogen, halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, amino, amino-C 1-6 alkyl, C 1-6 alkyl-carbonyl-amino, C 3-14 cycloalkyl, C 3-14 cycloalkyloxy, C 3-14 cycloalkyl-C 1-6 alkyl, aryl, aryloxy, aryloxy-C 1-6 alkyl, heteroaryl, heteroaryl-C 1-6 alkyl, heterocyclyl, heterocyclyl-C 1-6 alkyl or heterocyclyl-carbonyl, 
         wherein each instance of amino is optionally substituted with one or two substituents each selected from C 1-6 alkyl, hydroxy-C 1-6 alkyl, carboxy-C 1-6 alkyl, aryl-C 1-6 alkyl, heterocyclyl-C 1-6 alkyl or aryl optionally substituted with one or two C 1-6 alkyl substituents, 
         wherein each instance of aryl is optionally substituted with one or two substituents each selected from halogen, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy or aryl optionally substituted with one or two C 1-6 alkyl substituents, and 
         wherein each instance of heterocyclyl is optionally substituted with one or two substituents each selected from C 1-6 alkyl or aryl optionally substituted with one or two C 1-6 alkyl substituents, or is optionally substituted on one or two carbon atoms with an oxo substituent. 
       
     
     
         52 . The method of  claim 51 , wherein
 R 2  is selected from hydrogen, aryl, heteroaryl or heterocyclyl,   wherein aryl is optionally substituted with one or two substituents each selected from halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy or C 1-6 alkoxy-carbonyl, or one substituent selected from halo-C 1-6 alkyl-amino, hydroxy-C 1-6 alkyl-amino, amino-carbonyl, aryl, heteroaryl or heterocyclyl optionally substituted with one oxo substituent,   wherein heteroaryl is optionally substituted with one or two C 1-6 alkyl substituents or one heterocyclyl substituent,   wherein heterocyclyl is optionally substituted with two halogen substituents, and   wherein R 2  is absent when Y is N; and   R 3  is one, two, or three carbon atom substituents each selected from hydrogen, halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, amino, amino-C 1-6 alkyl, C 1-6 alkyl-carbonyl-amino, aryl, aryloxy, aryloxy-C 1-6 alkyl, heteroaryl, heteroaryl-C 1-6 alkyl, heterocyclyl or heterocyclyl-carbonyl,   wherein each instance of amino is optionally substituted with one or two substituents each selected from C 1-6 alkyl, hydroxy-C 1-6 alkyl, carboxy-C 1-6 alkyl, aryl-C 1-6 alkyl, heterocyclyl-C 1-6 alkyl or aryl optionally substituted with one or two C 1-6 alkyl substituents,   wherein each instance of aryl is optionally substituted with one or two substituents each selected from halogen, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkoxy or halo-C 1-6 alkoxy, and   wherein each instance of heterocyclyl is optionally substituted with one or two C 1-6 alkyl substituents, or is optionally substituted on a carbon atom with an oxo substituent.   
     
     
         53 . The method of  claim 51 , wherein
 R 1  is selected from hydrogen or phenyl, wherein phenyl is optionally substituted with carboxyl and, wherein R 1  is absent when Z is N;   R 2  is selected from hydrogen, phenyl, furanyl, thienyl, pyridinyl, 2,3-dihydro-benzofuranyl or benzo[1,3]dioxolyl,   wherein phenyl is optionally substituted with one or two substituents each selected from halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkoxy or C 1-6 alkoxy-carbonyl, or one substituent selected from halo-C 1-6 alkyl-amino, hydroxy-C 1-6 alkyl-amino, amino-carbonyl, phenyl, pyrazolyl, azetidinyl, pyrrolidinyl or morpholinyl, optionally substituted on pyrrolidinyl with one oxo substituent,   wherein furanyl, thienyl and pyridinyl is optionally substituted with one or two C 1-6 alkyl substituents or one azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl substituent,   wherein benzo[1,3]dioxolyl is optionally substituted with two halogen substituents, and   wherein R 2  is absent when Y is N; and   R 3  is one, two, or three carbon atom substituents each selected from hydrogen, halogen, carboxyl, C 1-6 alkyl, C 1-6 alkoxy, amino, amino-C 1-6 alkyl, C 1-6 alkyl-carbonyl-amino, phenyl, phenyloxy, phenyloxy-C 1-6 alkyl, imidazolyl, pyrazolyl, 1H-1,2,4-triazolyl, benzofuranyl, imidazolyl-C 1-6 alkyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, 1,4-diazepanyl, 2,3-dihydro-indolyl, 3,4-dihydroisoquinolin-(1H)-yl, 1,4-dioxa-8-azaspiro[4.5]decanyl, pyrrolidinyl-carbonyl or morpholinyl-carbonyl,   wherein each instance of amino is optionally substituted with one or two substituents each selected from C 1-6 alkyl, hydroxy-C 1-6 alkyl, carboxy-C 1-6 alkyl, phenyl-C 1-6 alkyl, benzo[1,3]dioxolyl-C 1-6 alkyl, or phenyl optionally substituted with one or two C 1-6 alkyl substituents,   wherein each instance of phenyl is optionally substituted with one or two substituents each selected from halogen, C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 alkoxy or halo-C 1-6 alkoxy, and   wherein each instance of azetidinyl, pyrrolidinyl, piperazinyl, morpholinyl or 1,4-diazepanyl is optionally substituted with one or two C 1-6 alkyl substituents, or is optionally substituted on one azetidinyl or pyrrolidinyl carbon atom with an oxo substituent.   
     
     
         54 . The method of  claim 51 , wherein the compound of Formula (I) or a form thereof is a compound of Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id), Formula (Ie) or Formula (If) or a form thereof, wherein all substituent variables are as previously defined: 
       
         
           
           
               
               
           
         
       
     
     
         55 . The method of  claim 38 , wherein the compound is:
 3-benzooxazol-2-yl-benzoic acid,   3-(6-methyl-benzooxazol-2-yl)-benzoic acid,   3-(5-phenyl-benzooxazol-2-yl)-benzoic acid,   3-[5-(4-isopropyl-3-methyl-phenoxymethyl)-benzooxazol-2-yl]-benzoic acid,   3-{5-[(4-isopropyl-phenylamino)-methyl]-benzooxazol-2-yl}-benzoic acid,   3-(5-tert-butyl-benzooxazol-2-yl)-benzoic acid,   3-(5-chloro-benzooxazol-2-yl)-benzoic acid,   3-(6-imidazol-1-ylmethyl-benzooxazol-2-yl)-benzoic acid,   3-(5-bromo-benzooxazol-2-yl)-benzoic acid,   4-(5-phenyl-benzooxazol-2-yl)-benzoic acid,   4-(6-methyl-benzooxazol-2-yl)-benzoic acid,   4-(5-chloro-benzooxazol-2-yl)-benzoic acid,   4-(5-tert-butyl-benzooxazol-2-yl)-benzoic acid,   2-(3-carboxy-phenyl)-benzooxazole-6-carboxylic acid,   2-(3-carboxy-phenyl)-benzooxazole-5-carboxylic acid,   3-[5-(morpholine-4-carbonyl)-benzooxazol-2-yl]-benzoic acid,   3-[6-(morpholine-4-carbonyl)-benzooxazol-2-yl]-benzoic acid,   2-biphenyl-4-yl-benzooxazole-6-carboxylic acid,   2-biphenyl-4-yl-benzooxazole-5-carboxylic acid,   4-(5-bromo-benzooxazol-2-yl)-benzoic acid,   3-(5-methyl-benzooxazol-2-yl)-benzoic acid,   3-[5-(1,1-dimethyl-propyl)-benzooxazol-2-yl]-benzoic acid,   3-(6-Phenyl-benzooxazol-2-yl)-benzoic acid,   2-(4-isopropyl-phenyl)-benzooxazole-5-carboxylic acid,   2-(4-isopropyl-phenyl)-benzooxazole-6-carboxylic acid,   2-benzo[1,3]dioxol-5-yl-benzooxazole-5-carboxylic acid,   2-biphenyl-4-yl-benzooxazole-7-carboxylic acid,   2-[4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzooxazole-5-carboxylic acid,   3-[5-(4-trifluoromethoxy-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-[5-(3,4-difluoro-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-(5-benzofuran-2-yl-benzooxazol-2-yl)-benzoic acid,   3-(5-methoxy-benzooxazol-2-yl)-benzoic acid,   3-(6-fluoro-benzooxazol-2-yl)-benzoic acid,   3-[6-(2,6-dimethyl-morpholin-4-yl)-benzooxazol-2-yl]-benzoic acid methyl ester,   2-(4-bromo-phenyl)-benzooxazole-5-carboxylic acid,   3-[5-(4-isopropyl-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-[5-(3,5-dimethyl-phenyl)-benzooxazol-2-yl]-benzoic acid,   2-p-tolyl-benzooxazole-5-carboxylic acid,   2-(4-methoxy-phenyl)-benzooxazole-5-carboxylic acid,   2-(4-pyrrolidin-1-yl-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-piperidin-1-yl-benzooxazol-2-yl)-benzoic acid,   3-(6-morpholin-4-yl-benzooxazol-2-yl)-benzoic acid,   3-(5-pyrrolidin-1-yl-benzooxazol-2-yl)-benzoic acid,   3-(6-pyrazol-1-yl-benzooxazol-2-yl)-benzoic acid,   3-[6-(2-oxo-azetidin-1-yl)-benzooxazol-2-yl]-benzoic acid,   3-[6-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-benzooxazol-2-yl]-benzoic acid,   2-[4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzooxazole-5-carboxylic acid,   3-[6-(4-methyl-piperazin-1-yl)-benzooxazol-2-yl]-benzoic acid,   3-(6-imidazol-1-yl-benzooxazol-2-yl)-benzoic acid,   3-[6-(2,3-dihydro-indol-1-yl)-benzooxazol-2-yl]-benzoic acid,   2-(4-morpholin-4-yl-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-azetidin-1-yl-benzooxazol-2-yl)-benzoic acid,   3-(6-pyrrolidin-1-yl-benzooxazol-2-yl)-benzoic acid,   2-[4-(3-chloro-propylamino)-phenyl]-benzooxazole-5-carboxylic acid,   2-(4-fluoro-phenyl)-benzooxazole-5-carboxylic acid,   2-(4-pyrazol-1-yl-phenyl)-benzooxazole-5-carboxylic acid,   2-(4-azetidin-1-yl-phenyl)-benzooxazole-5-carboxylic acid,   2-phenyl-oxazolo[4,5-b]pyridine,   6-bromo-2-phenyl-oxazolo[4,5-b]pyridine,   3-(6-[1,2,4]triazol-1-yl-benzooxazol-2-yl)-benzoic acid,   3-[6-(2-hydroxy-ethylamino)-benzooxazol-2-yl]-benzoic acid,   3-[5-(2-oxo-pyrrolidin-1-yl)-benzooxazol-2-yl]-benzoic acid,   2-[4-(3-hydroxy-propylamino)-phenyl]-benzooxazole-5-carboxylic acid,   2-phenyl-benzooxazole-6-carboxylic acid,   2-furan-2-yl-benzooxazole-6-carboxylic acid,   2-(2-fluoro-phenyl)-benzooxazole-6-carboxylic acid,   2-(2,5-dimethyl-furan-3-yl)-benzooxazole-6-carboxylic acid,   2-pyridin-4-yl-benzooxazole-6-carboxylic acid,   2-pyridin-3-yl-benzooxazole-6-carboxylic acid,   2-(3-methyl-thiophen-2-yl)-benzooxazole-6-carboxylic acid,   3-[6-(pyrrolidine-1-carbonyl)-benzooxazol-2-yl]-benzoic acid,   3-[6-(5-hydroxy-pentylamino)-benzooxazol-2-yl]-benzoic acid,   3-(6-phenethylamino-benzooxazol-2-yl)-benzamide,   3-[6-(3-phenyl-propylamino)-benzooxazol-2-yl]-benzoic acid,   2-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-benzooxazole-6-carboxylic acid,   3-oxazolo[4,5-b]pyridin-2-yl-benzoic acid,   2-(2,5-dimethyl-furan-3-yl)-benzooxazole-5-carboxylic acid,   2-furan-2-yl-benzooxazole-5-carboxylic acid,   2-benzo[1,3]dioxol-5-yl-benzooxazole-6-carboxylic acid,   3-[6-(6-hydroxy-hexylamino)-benzooxazol-2-yl]-benzoic acid,   3-[6-(4-methyl-[1,4]diazepan-1-yl)-benzooxazol-2-yl]-benzoic acid,   3-(6-phenoxy-benzooxazol-2-yl)-benzoic acid,   3-[6-(4-hydroxy-butylamino)-benzooxazol-2-yl]-benzoic acid,   3-(6-phenethylamino-benzooxazol-2-yl)-benzoic acid,   2-(2-pyrrolidin-1-yl-pyridin-3-yl)-benzooxazole-6-carboxylic acid,   2-(3,4-dimethoxy-phenyl)-benzooxazole-6-carboxylic acid,   2-(6-morpholin-4-yl-pyridin-3-yl)-benzooxazole-6-carboxylic acid,   2-(3,4-dimethoxy-phenyl)-benzooxazole-5-carboxylic acid,   2-(6-pyrrolidin-1-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid,   2-(6-morpholin-4-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid,   2-(3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-5′-yl)-benzooxazole-5-carboxylic acid,   2-(6-azetidin-1-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid,   2-(6-azetidin-1-yl-pyridin-3-yl)-benzooxazole-6-carboxylic acid,   2-(3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-5′-yl)-benzooxazole-6-carboxylic acid,   2-(2,3-dihydro-benzofuran-5-yl)-benzooxazole-6-carboxylic acid,   2-(6-piperazin-1-yl-pyridin-3-yl)-benzooxazole-6-carboxylic acid,   2-(2,3-dihydro-benzofuran-5-yl)-benzooxazole-5-carboxylic acid,   2-(4-trifluoromethoxy-phenyl)-benzooxazole-6-carboxylic acid,   2-(3-methoxy-phenyl)-benzooxazole-6-carboxylic acid,   2-(4-trifluoromethoxy-phenyl)-benzooxazole-5-carboxylic acid,   2-(3-methoxy-phenyl)-benzooxazole-5-carboxylic acid,   3-[6-(benzyl-methyl-amino)-benzooxazol-2-yl]-benzoic acid,   3-{6-[(benzo[1,3]dioxol-5-ylmethyl)-amino]-benzooxazol-2-yl}-benzoic acid,   2-(3-trifluoromethoxy-phenyl)-benzooxazole-6-carboxylic acid,   2-(3-trifluoromethoxy-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-phenylamino-benzooxazol-2-yl)-benzamide,   3-(6-phenoxy-benzooxazol-2-yl)-benzamide,   3-(6-fluoro-benzooxazol-2-yl)-benzamide,   3-(6-morpholin-4-yl-benzooxazol-2-yl)-benzamide,   3-(6-piperidin-1-yl-benzooxazol-2-yl)-benzamide,   3-(6-methoxy-benzooxazol-2-yl)-benzamide,   3-(6-methyl-benzooxazol-2-yl)-benzamide,   4-(6-methyl-benzooxazol-2-yl)-benzamide,   3-(6-phenethylamino-benzooxazol-2-yl)-benzamide,   4-(5-isopropyl-benzo[d]isoxazol-3-yl)-benzoic acid,   3-(5-isopropyl-benzo[d]isoxazol-3-yl)-benzoic acid,   3-(5-methoxy-benzo[d]isoxazol-3-yl)-benzoic acid,   4-(6-methoxy-benzo[d]isoxazol-3-yl)-benzoic acid,   3-(6-methoxy-benzo[d]isoxazol-3-yl)-benzoic acid,   3-(6-phenyl-benzo[d]isoxazol-3-yl)-benzoic acid,   4-(6-phenyl-benzo[d]isoxazol-3-yl)-benzoic acid,   3-(6-p-tolyl-benzo[d]isoxazol-3-yl)-benzoic acid,   4-(6-p-tolyl-benzo[d]isoxazol-3-yl)-benzoic acid,   4-[6-(4-fluoro-phenyl)-benzo[d]isoxazol-3-yl]-benzoic acid,   3-[6-(4-fluoro-phenyl)-benzo[d]isoxazol-3-yl]-benzoic acid,   3-[6-(4-trifluoromethoxy-phenyl)-benzo[d]isoxazol-3-yl]-benzoic acid,   3-[6-(4-trifluoromethyl-phenyl)-benzo[d]isoxazol-3-yl]-benzoic acid,   N-[2-(4-bromo-3-methyl-phenyl)-benzooxazol-5-yl]-acetamide,   or a pharmaceutically acceptable free acid, free base, salt, hydrate, solvate, clathrate, racemate, stereoisomer, or polymorph thereof.   
     
     
         56 . The method of  claim 38 , wherein the compound is:
 3-(6-methyl-benzooxazol-2-yl)-benzoic acid,   3-(5-tert-butyl-benzooxazol-2-yl)-benzoic acid,   3-(6-imidazol-1-ylmethyl-benzooxazol-2-yl)-benzoic acid,   4-(6-methyl-benzooxazol-2-yl)-benzoic acid,   2-biphenyl-4-yl-benzooxazole-6-carboxylic acid,   2-biphenyl-4-yl-benzooxazole-5-carboxylic acid,   3-(5-methyl-benzooxazol-2-yl)-benzoic acid,   3-[5-(1,1-dimethyl-propyl)-benzooxazol-2-yl]-benzoic acid,   3-(6-Phenyl-benzooxazol-2-yl)-benzoic acid,   2-(4-isopropyl-phenyl)-benzooxazole-5-carboxylic acid,   2-benzo[1,3]dioxol-5-yl-benzooxazole-5-carboxylic acid,   2-[4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzooxazole-5-carboxylic acid,   3-[5-(4-trifluoromethoxy-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-[5-(3,4-difluoro-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-(5-benzofuran-2-yl-benzooxazol-2-yl)-benzoic acid,   3-(5-methoxy-benzooxazol-2-yl)-benzoic acid,   2-(4-bromo-phenyl)-benzooxazole-5-carboxylic acid,   3-[5-(4-isopropyl-phenyl)-benzooxazol-2-yl]-benzoic acid,   3-[5-(3,5-dimethyl-phenyl)-benzooxazol-2-yl]-benzoic acid,   2-p-tolyl-benzooxazole-5-carboxylic acid,   2-(4-methoxy-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-piperidin-1-yl-benzooxazol-2-yl)-benzoic acid,   3-(6-morpholin-4-yl-benzooxazol-2-yl)-benzoic acid,   3-(5-pyrrolidin-1-yl-benzooxazol-2-yl)-benzoic acid,   3-(6-pyrazol-1-yl-benzooxazol-2-yl)-benzoic acid,   3-[6-(4-methyl-piperazin-1-yl)-benzooxazol-2-yl]-benzoic acid,   2-(4-morpholin-4-yl-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-azetidin-1-yl-benzooxazol-2-yl)-benzoic acid,   2-[4-(3-chloro-propylamino)-phenyl]-benzooxazole-5-carboxylic acid,   2-(4-fluoro-phenyl)-benzooxazole-5-carboxylic acid,   2-(4-azetidin-1-yl-phenyl)-benzooxazole-5-carboxylic acid,   2-furan-2-yl-benzooxazole-6-carboxylic acid,   2-(2-fluoro-phenyl)-benzooxazole-6-carboxylic acid,   2-(2,5-dimethyl-furan-3-yl)-benzooxazole-6-carboxylic acid,   2-pyridin-3-yl-benzooxazole-6-carboxylic acid,   3-[6-(pyrrolidine-1-carbonyl)-benzooxazol-2-yl]-benzoic acid,   3-(6-phenethylamino-benzooxazol-2-yl)-benzamide,   2-(2,5-dimethyl-furan-3-yl)-benzooxazole-5-carboxylic acid,   3-[6-(4-methyl-[1,4]diazepan-1-yl)-benzooxazol-2-yl]-benzoic acid,   3-(6-phenoxy-benzooxazol-2-yl)-benzoic acid,   2-(6-pyrrolidin-1-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid,   2-(6-morpholin-4-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid,   2-(3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-5′-yl)-benzooxazole-5-carboxylic acid,   2-(6-azetidin-1-yl-pyridin-3-yl)-benzooxazole-6-carboxylic acid,   2-(4-trifluoromethoxy-phenyl)-benzooxazole-5-carboxylic acid,   3-[6-(benzyl-methyl-amino)-benzooxazol-2-yl]-benzoic acid,   2-(3-trifluoromethoxy-phenyl)-benzooxazole-5-carboxylic acid,   3-(6-phenylamino-benzooxazol-2-yl)-benzamide,   3-(6-piperidin-1-yl-benzooxazol-2-yl)-benzamide,   3-(6-methoxy-benzooxazol-2-yl)-benzamide,   3-(6-methyl-benzooxazol-2-yl)-benzamide,   N-[2-(4-bromo-3-methyl-phenyl)-benzooxazol-5-yl]-acetamide,   or a pharmaceutically acceptable free acid, free base, salt, hydrate, solvate, clathrate, racemate, stereoisomer, or polymorph thereof.   
     
     
         57 . The method of  claim 38 , wherein the compound is:
 2-(4-isopropyl-phenyl)-benzooxazole-5-carboxylic acid,   3-(5-methoxy-benzooxazol-2-yl)-benzoic acid,   2-p-tolyl-benzooxazole-5-carboxylic acid,   3-(6-piperidin-1-yl-benzooxazol-2-yl)-benzoic acid,   2-(2-fluoro-phenyl)-benzooxazole-6-carboxylic acid,   2-(6-pyrrolidin-1-yl-pyridin-3-yl)-benzooxazole-5-carboxylic acid, or   N-[2-(4-bromo-3-methyl-phenyl)-benzooxazol-5-yl]-acetamide.   
     
     
         58 . The method of  claim 38 , wherein the compound is N-[2-(4-bromo-3-methyl-phenyl)-benzooxazol-5-yl]-acetamide.