α-ketoamide derivatives useful endothelial lipase inhibitors

A compound of formula (I)

• wherein
• R1 is an aromatic ring selected from the group consisting of phenyl, pyridyl, pyrimidinyl, thiazolyl, and quinolinyl;
• wherein the aromatic ring is optionally substituted with one to two substituents independently selected from the group consisting of halogen, C1-4alkyl, trifluoromethyl, C1-4alkoxy, trifluoromethoxy, cyano, —C(O)—NRARB, —NH—C(O)—(C1-4alkyl), and phenyl;
• and wherein RA and RB are each independently selected from the group consisting of hydrogen and C1-4 alkyl;
• L1 is selected from the group consisting of -(n-pentyl)-, -(n-hexyl)-, —O—(n-pentyl)-, —NH-(n-pentyl)-,—CH═CH-(n-propyl)-, —CH═CH-(n-butyl)-, —CC-(n-propyl)- and —CC-(n-butyl)-;
• X is selected from the group consisting of —NH—, —O— and —S—;
• is selected from the group consisting of
• (a)
• a is an integer from 0 to 2;
• each R4 is independently selected from the group consisting of halogen, C1-4alkyl, trifluoromethoxy, NR6R7, —C(O)—NH—CH2CH2—NR6R7 and phenyl;
• wherein R6 and R7 are each independently selected form the group consisting of hydrogen and C1-4alkyl;
• wherein the R4 phenyl is optionally substituted with one to three substituents independently selected from the group consisting of halogen, C1-4alkyl, trifluoromethyl, C1-4alkoxy and trifluoromethoxy;
• (b)
• L2 is selected from the group consisting of —O—, —NR7— and —S(O)—;
• wherein R7 is selected from the group consisting of hydrogen, C1-4alkyl and t-butoxycarbonyl;
• R5 is an aromatic ring structure selected from the group consisting of phenyl, benzyl, phenylethyl-, imidazolyl, imidazolyl-methyl-, pyridyl, pyridyl-methyl-, pyrimidinyl, pyrimidinyl-methyl-, furyl, furylmethyl-, quinolinyl, quinolinyl-methyl-, benzo[d][1,2,3]triazolyl and benzo[d][1,2,3]triazolyl-methyl-;
• wherein the R5 aromatic ring structure is optionally substituted with one to two substituents independently selected from the group consisting of halogen, C1-4alkyl, trifluoromethyl, C1-4alkoxy, trifluoromethoxy, —C(O)OH, —C(O)—O—C1-4alkyl, cyano, and —C(O)—NR8R9;
• wherein R8 and R9 are each independently selected from the group consisting of hydrogen and C1-4alkyl;
• alternatively R5 is 4-(pyrid-4-yl-N-oxide-methoxy)-phenyl;
• and wherein the -L2-R5 group is bound at the 3- or 4-position;
• (c) naphth-2-yl;
• and
• (d) a heteroaryl selected from the group consisting of pyridyl, benzo[d][1,3]dioxolyl, dibenzo[b,e][1,4]dioxinyl, and 2,3-dihydropyrrolo[2,1-b]quinazolin-9-one;
• or a pharmaceutically acceptable salt thereof.