主权项 |
1. At least one chemical entity chosen from compounds of Formula Iand pharmaceutically acceptable salts and prodrugs thereof wherein:
X and Y are independently chosen from —N— and —CH—, provided that at least one of X and Y is —N—; R1 is aryl or monocyclic heteroaryl, each of which is substituted with
a first group of the formula —Z—R6 wherein
Z is chosen from —O—, —S—, —S(O)—, —S(O)2—, —CR11R12—, —OCR11R12—, —NR13—, —NR13CR11R12—, —CR11R12NR13—, and —C(O)— where R11, R12, and R13 are independently chosen from hydrogen, lower alkyl, hydroxyl, and lower alkoxy,R6 is chosen from hydrogen, optionally substituted C1-C6 alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted heterocycloalkyl, provided that if Z is —O—, then R6 is not optionally substituted benzyl or optionally substituted pyridylmethyl, orR6 and R13, taken together with the nitrogen to which they are bound form an optionally substituted 5- to 7-membered heterocycloalkyl ring, anda second group chosen from halo and lower alkyl optionally substituted with halo, or R1 is chosen from: 2,3-dihydrobenzofuran-5-yl, chroman-6-yl, 1,3-benzodioxol-5-yl, 2,3-dihydro-1,4-benzodioxin-6-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl, 2-oxo-2,3-dihydro-1,3-benzoxazol-5-yl, benzothiophen-5-yl, benzothiazol-5-yl, benzoimidazol-5-yl, benzofuran-5-yl, 1H-indol-5-yl, 1H-indazol-5-yl, isoindolin-5-yl, benzo[c][1,2,5]oxadiazol-5-yl, 1,2,3,4-tetrahydroquinolin-6-yl, imidazo[1,2-a]pyridin-6-yl, pyrazolo[1,5-a]pyridine-5-yl, quinolin-6-yl, quinazolin-6-yl, quinazolin-7-yl, and quinoxalin-6-yl, each of which is optionally substituted, or R1 and R3, taken together with intervening atoms form a bicyclic ring of the formula which is optionally substituted where m is 0 or 1 and n is 0 or 1, provided that at least one of m and n is 1 and W is —O—, or —N(R8)— where R8 is hydrogen or lower alkyl; R2 is chosen from hydrogen and optionally substituted lower alkyl; R3 is chosen from hydrogen, halo, optionally substituted lower alkyl, hydroxyl, optionally substituted lower alkoxy, and optionally substituted amino; L is chosen from —C(O)—, —C(O)O—, —C(O)N(R4)—, —C(O)N(OR7)—, —N(R4)S(O)2—, —S(O)2N(R4)—, and —C(O)N(R4)—S(O)2—; R4 is chosen from hydrogen and lower alkyl; R5 is chosen from hydrogen, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and optionally substituted heterocycloalkyl; provided that when L is —N(R4)S(O)2—, then R5 is not hydrogen, or R4 and R5 taken together with the nitrogen to which they are bound form an optionally substituted 4- to 7-membered heterocycloalkyl ring, which is optionally fused to an optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl ring; or R3 and R5, taken together with the intervening atoms, form an optionally substituted 5- to 7-membered ring; and R7 is chosen from hydrogen and lower alkyl; provided that the compound of Formula I is not chosen from 6-(3-chloro-4-methyl-phenyl)-pyrimidine-4-carboxylic acid methyl ester; 6-(3-chloro-4-methyl-phenyl)-pyrimidine-4-carboxylic acid; 6-(3-chloro-4-methoxy-phenyl)-pyrimidine-4-carboxylic acid methyl ester; and 6-(3-chloro-4-methoxy-phenyl)-pyrimidine-4-carboxylic acid. |