Biaryl substituted heterocycle inhibitors of LTA4H for treating inflammation

A compound of formula:

• wherein
• Ar is selected from the group consisting of
• phenyl;
• and
• phenyl substituted with from one to three substituents independently selected from the group consisting of halogen, loweralkyl, loweracyl, loweralkoxy, fluoroloweralkyl, fluoroloweralkoxy, hydroxy, hydroxy(C1-C4)alkyl, formyl, formyl(C1-C4)alkyl, cyano, cyano(C1-C4)alkyl, benzyl, benzyloxy, phenyl, substituted phenyl, heteroaryl, heterocyclylalkyl, substituted heteroaryl, and nitro;
• X is selected from the group consisting of direct bond, O, SO, S(O2), NR1, CH2, CF2, CH2CH2, CH2NR1, NR1CH2, CH═CH, C═O, CH2C═O, CR1aR1b, OCR1aR1b, CR1aR1bO;
• SO2NR1, NR1SO2, C(═O)NR1 and NR1C(═O);
• R1 is selected separately in each occurrence from the group consisting of H and lower alkyl;
• R1a is selected from the group consisting of H, OH and lower alkyl;
• R1b is selected from the group consisting of H and lower alkyl, or R1a and R1b taken together may form a 3-6 membered ring, which may optionally contain a heteroatom chosen from O, S, and N;
• HetAr is a phenyl ring attached via a ring carbon to Q, further characterized in that Q and X cannot be on adjacent positions in said aryl ring;
• Q is —O—;
• n is an integer selected from 1-5;
• HET is selected from the group consisting of
• pyrrolidine and
• pyrrolidine substituted with one or two substituents independently selected from the group consisting of halogen, hydroxyl, amino, carboxy, loweralkyl, loweracyl, loweralkoxy, N-oxide, fluoroloweralkyl, fluoroloweralkoxy, formyl, cyano, benzyl, benzyloxy, phenyl, heteroaryl and nitro;
• and
• taken together ZW is H or
• Z is (CH2)1-10, in which one or two (CH2) may optionally be replaced by —O—, —NR1—, —SO—, —S(O)2—, —C(═O)— or —C═O(NH)—, provided that said —O—, —NR1—, —SO—, —S(O)2—, —C(═O)— or —C═O(NH)— are not at the point of attachment to HET and are separated by at least one —(CH2)—;
• W is selected from the group consisting of acyl, hydroxyl, carboxyl, amino, —C(O)NHR4, aminoacyl, —COOalkyl, —CHO, heterocyclyl, substituted aryl, substituted heterocyclyl, sulfonamide, —C(O)fluoroalkyl, —C(O)CH2C(O)Oalkyl, —C(O)CH2C(O)Ofluoroalkyl, —SH, —C(O)NH(OH), —C(O)N(OH)R4, —N(OH)C(O)OH, —N(OH)C(O)R4;
• and
• R4 is selected from the group consisting of H, (C1-C4) alkyl, and phenyl(C1-C4) alkyl;
• with the provisos that;
• (a) when HET is (S)-pyrrolidine or rac-pyrrolidine Ar is phenyl or halo-substituted phenyl, and HetAr is p-phenylene, then the Z—W combination is other than H.