Patent ID: 6686376
Filing Date: 2004-02-03
Classification: A61P,C07D

Abstract:
A method of inhibiting MRP1 in a mammal which comprises administering to a mammal in need thereof an effective amount of a compound of formula I: wherein:E is a bond or â€”C(R4)(R4)â€”; R1 is independently at each occurrence hydrogen or C1-C6 alkyl; R2 is independently at each occurrence hydrogen or C1-C6 alkyl; R3 is independently at each occurrence hydrogen, C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted (C1-C4 alkyl) C3-C8 cycloalkyl, optionally substituted (C1-C4 alkyl)-aryl, optionally substituted aryl, optionally substituted (C1-C4 alkyl)-heterocycle, optionally substituted heterocycle, C1-C6 alkoxy, optionally substituted Oâ€”(C3-C8 cycloalkyl), optionally substituted (C1-C4 alkoxy) C3-C8 cycloalkyl, optionally substituted (C1-C4 alkoxy)-aryl, optionally substituted O-aryl, optionally substituted (C1-C4 alkoxy)-heterocycle, or optionally substituted O-heterocycle; R4 is independently at each occurrence hydrogen or C1-C6 alkyl; R5 is independently at each occurrence hydrogen or C1-C6 alkyl; or a pharmaceutical salt thereof wherein: optionally substituted C3-C8 cycloalkyl refers to a C3-C8 cycloalkyl unsubstituted or substituted once with a phenyl, substituted phenyl, or CO2R1 group; optionally substituted (C1-C4 alkyl)-(C3-C8 cycloalkyl) refers to optionally substituted C3-C8 cycloalkyl linked through a C1-C4 alkyl, optionally substituted with halo or hydroxy; optionally substituted C6-C10 bicycloalkyl refers to a C6-C10 bicycloalkyl unsubstituted or substituted once with a phenyl, substituted phenyl, or CO2R1 group; optionally substituted aryl refers to a phenyl and naphthyl group respectively optionally substituted from 1 to 5 times independently with C1-C6 alkyl, C1-C4 alkoxy, halo, hydroxy, trifluoromethyl, NR4R5, SO2N(R13)2, NHâ€”Pg, C1-C6 alkoxy, benzyloxy, C(O)R13, C5-C7 cycloalkyl, trifluoromethoxy, SR1, cyano, or nitro; optionally substituted (C1-C4 alkyl)-aryl refers to optionally substituted aryl linked through a C1-C4 alkyl, optionally substituted with halo, trifluoromethyl, or hydroxy; optionally substituted phenoxy refers to a phenoxy group optionally substituted from 1 to 3 times independently with C1-C6 alkyl, halo, hydroxy, trifluoromethyl, NR4R6, SO2N(R13)2, NHâ€”Pg, C1-C6 alkoxy, benzyloxy, C(O)R13, C5-C7 cycloalkyl, trifluoromethoxy, or nitro; optionally substituted (C1-C4 alkyl)-phenoxy refers to optionally substituted phenoxy linked through a C1-C4 alkyl, optionally substituted with halo, trifluoromethyl, or hydroxy; heterocycle is taken to mean stable unsaturated and saturated 3 to 6 membered rings containing from 1 to 4 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, said rings being optionally benzofused. All of these rings may be substituted with up to three substituents independently selected from the group consisting of halo, C1-C4 alkoxy, C1-C4 alkyl, cyano, nitro, hydroxy, â€”S(O)mâ€”(C1-C4 alkyl) and â€”S(O)m-phenyl where m is 0, 1 or 2; heteroaryl is taken to mean an unsaturated or benzofused unsaturated heterocycle; substituted heterocycle refers to a heterocyclic ring substituted 1 or 3 times independently with a C1-C6 alkyl, halo, benzyl, phenyl, trifluoromethyl. Saturated heterocyclic rings may be additionally substituted 1 or 2 times with an oxo group, however, total substitution of the saturated heterocyclic ring may not exceed two substituents; and optionally substituted (C1-C4 alkyl)-heterocycle refers to optionally substituted heterocycle linked through a C1-C4 alkyl, optionally substituted with halo or hydroxy.