Substituted quinoxalines as inhibitors of fatty acid binding protein

摘要

The present invention relates to novel quinoxaline compounds of Formula I:;
as Fatty Acid Binding Protein (“FABP”) inhibitors, pharmaceutical compositions comprising the quinoxaline compounds and the use of the quinoxaline compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose.

主权项

1. A compound of the formula I: or a pharmaceutically acceptable salt thereof, wherein:
wherein X and Y represent carbon atoms and Z represents a nitrogen atom;each R1 is H or is selected from the group consisting of: halo, CN, OH, C1-6alkyl, OC1-6alkyl, haloC1-6alkyl, OC1-6haloalkyl, S(O)xC1-6alkyl, and S(O)xC1-6haloalkyl, wherein x is 0, 1 or 2;
R2 represents OH, halo, C1-6alkyl, OC1-6alkyl, C1-6haloalkyl, OC1-6haloalkyl, NH2, NHC1-6alkyl and N(C1-6alkyl)2, the alkyl portions of NHC1-6alkyl and N(C1-6alkyl)2 being optionally substituted with 1-3 halo atoms;R3 and R4 taken together with the N atom to which they are attached represent a 4-7 membered ring consisting of carbon atoms and 1 N atom, wherein the 4-7 membered ring is substituted with 1-3 groups selected from Rb; each Rb is selected from the group consisting of: a) C1-6alkyl optionally substituted with 1-2 Aryl, Heteroaryl, Heterocyclyl, Cycloalkyl, O—C1-6Alkyl, O-Aryl, O-Heteroaryl, NH—C1-6Alkyl, NH-Aryl, and NH-Heteroaryl groups, the Aryl, Heteroaryl, Heterocyclyl and Alkyl portions being further optionally substituted with 1-3 C1-3alkyl, halo, OC1-6alkyl, C1-6haloalkyl and OC1-6haloalkyl groups; b) CO2C1-6Alkyl, CO2-Aryl, CO2-Heteroaryl, and CO2C3-6Cycloalkyl, each being optionally substituted with 1-2 C1-3 alkyl, halo, Aryl, Heteroaryl, Heterocyclyl, Cycloalkyl, O—C1-6Alkyl, NH—C1-6Alkyl, and NH-Aryl groups, the Aryl, Heteroaryl, and Heterocyclyl portions, and the alkyl portions of O—C1-6Alkyl and NH—C1-6Alkyl being further optionally substituted with 1-3 C1-6alkyl, halo, OC1-6alkyl, haloC1-6alkyl and OC1-6haloalkyl groups; c) Aryl, Heteroaryl, Heterocyclyl, Cycloalkyl, O—C1-6Alkyl, NH—C1-6Alkyl, and NH-Aryl, each being optionally substituted with 1-3 alkyl, halo, OC1-6alkyl, haloC1-6alkyl and OC1-6haloalkyl groups;
or 2 Rb groups are taken together and represent a fused phenyl ring, optionally substituted with 1-3 halo atoms or C1-6alkyl groups.