A compound of formula I: where: R 1 is selected from H, -C 1-8 alkyl, -C 1-3 alkylene-C 6-10 aryl, -C 1-3 alkylene-C 1-9 heteroaryl, -C 3-7 cycloalkyl, -[(CH 2) 2 O] 1-3 CH 3, -C 1-6 alkylene-OC R 10, -C 1-6 alkylene-NR 11 R 12, -C 1-6 alkylene-C R 13, -C 0-6 alkylenemorpholinyl, -C 1-6 alkylene-SO 2 -C 1-6 alkyl, R 10 is selected from -C 1-6 alkyl, -O-C 1-6 alkyl, -C 3-7 cycloalkyl, -O-C 3-7 cycloalkyl, phenyl, -O-phenyl, -NR 11 R 12, -CH(R 15)-NH 2, -CH(R 15)-NHC O-C 1-6 alkyl, and -CH(NH 2)CH 2 COOCH 3; and R 11 and R 12 are independently selected from H, -C 1-6 alkyl, and benzyl; or R 11 and R 12 are taken together as -(CH 2) 3-6 -, -C -(CH 2) 3 -, or -(CH 2) 2 O(CH 2) 2 -; R 13 is selected from -O-C 1-6 alkyl, -O-benzyl, and -NR 11 R 12; and R 14 is -C 1-6 alkyl or -C 0-6 alkylene-C 6-10 aryl; R 15 is H, -CH 3, -CH(CH 3) 2, phenyl, or benzyl; R 2 is -OR 21 or -CH 2 OR 21, and R 3 is H or -CH 3; where R 21 is H, -C -C 1-6 alkyl, -C -CH(R 22)-NH 2, -C -CH(R 22)-NHC O-C 1-6 alkyl, or -P (OR 23) 2; R 22 is H, -CH 3, -CH(CH 3) 2, phenyl, or benzyl; R 23 is H, -C 1-6 alkyl, or phenyl; or R 2 is taken together with R 1 to form -OCR 15 R 16 - or -CH 2 O-CR 15 R 16 -, and R 3 is selected from H and -CH 3, where R 15 and R 16 are independently selected from H, -C 1-6 alkyl, and -O-C 3-7 cycloalkyl, or R 15 and R 16 are taken together to form =O; or R 2 is taken together with R 3 to form -CH 2 -O-CH 2 - or -CH 2 -CH 2 -; or R 2 and R 3 are both -CH 3; Z is selected from -CH- and -N-; R 4 is selected from H, -C 1-8 alkyl, -C 1-3 alkylene-O-C 1-8 alkyl, -C 1-3 alkylene-C 6-10 aryl, -C 1-3 alkylene-O-C 6-10 aryl, -C 1-3 alkylene-C 1-9 heteroaryl, -C 3-7 cycloalkyl, -[(CH 2) 2 O] 1-3 CH 3, -C 1-6 alkylene-OC R 40, -C 1-6 alkylene-NR 41 R 42, -C 1-6 alkylene-C R 43, -C 0-6 alkylenemorpholinyl, -C 1-6 alkylene-SO 2 -C 1-6 alkyl, R 40 is selected from -C 1-6 alkyl, -O-C 1-6 alkyl, -C 3-7 cycloalkyl, -O-C 3-7 cycloalkyl, phenyl, -O-phenyl, -NR 41 R 42, -CH(R 45)-NH 2, -CH(R 45)-NHC O-C 1-6 alkyl, and -CH(NH 2)CH 2 COOCH 3; and R 41 and R 42 are independently selected from H, -C 1-6 alkyl, and benzyl; or R 41 and R 42 are taken together as -(CH 2) 3-6 -, -C -(CH 2) 3 -, or -(CH 2) 2 O(CH 2) 2 -; R 43 is selected from -O-C 1-6 alkyl, -O-benzyl, and -NR 41 R 42; and R 44 is -C 1-6 alkyl or -C 0-6 alkylene-C 6-10 aryl; R 45 is H, -CH 3, -CH(CH 3) 2, phenyl, or benzyl; a is 0 or 1; R 5 is selected from halo, -CH 3, -CF 3, and -CN; b is 0 or an integer from 1 to 3; each R 6 is independently selected from halo, -OH, -CH 3, -OCH 3, -CN, and -CF 3; where each alkyl group in R 1 and R 4 is optionally substituted with 1 to 8 fluoro atoms; and where the methylene linker on the biphenyl is optionally substituted with one or two -C 1-6 alkyl groups or cyclopropyl; or a pharmaceutically acceptable salt thereof. R 1 is selected from H, -C 1-8 alkyl, -C 1-3 alkylene-C 6-10 aryl, -C 1-3 alkylene-C 1-9 heteroaryl, -C 3-7 cycloalkyl, -[(CH 2) 2 O] 1-3 CH 3, -C 1-6 alkylene-OC R 10, -C 1-6 alkylene-NR 11 R 12, -C 1-6 alkylene-C R 13, -C 0-6 alkylenemorpholinyl, -C 1-6 alkylene-SO 2 -C 1-6 alkyl, R 10 is selected from -C 1-6 alkyl, -O-C 1-6 alkyl, -C 3-7 cycloalkyl, -O-C 3-7 cycloalkyl, phenyl, -O-phenyl, -NR 11 R 12, -CH(R 15)-NH 2, -CH(R 15)-NHC O-C 1-6 alkyl, and -CH(NH 2)CH 2 COOCH 3; and R 11 and R 12 are independently selected from H, -C 1-6 alkyl, and benzyl; or R 11 and R 12 are taken together as -(CH 2) 3-6 -, -C -(CH 2) 3 -, or -(CH 2) 2 O(CH 2) 2 -; R 13 is selected from -O-C 1-6 alkyl, -O-benzyl, and -NR 11 R 12; and R 14 is -C 1-6 alkyl or -C 0-6 alkylene-C 6-10 aryl; R 15 is H, -CH 3, -CH(CH 3) 2, phenyl, or benzyl; R 2 is -OR 21 or -CH 2 OR 21, and R 3 is H or -CH 3; where R 21 is H, -C -C 1-6 alkyl, -C -CH(R 22)-NH 2, -C -CH(R 22)-NHC O-C 1-6 alkyl, or -P (OR 23) 2; R 22 is H, -CH 3, -CH(CH 3) 2, phenyl, or benzyl; R 23 is H, -C 1-6 alkyl, or phenyl; or R 2 is taken together with R 1 to form -OCR 15 R 16 - or -CH 2 O-CR 15 R 16 -, and R 3 is selected from H and -CH 3, where R 15 and R 16 are independently selected from H, -C 1-6 alkyl, and -O-C 3-7 cycloalkyl, or R 15 and R 16 are taken together to form =O; or R 2 is taken together with R 3 to form -CH 2 -O-CH 2 - or -CH 2 -CH 2 -; or R 2 and R 3 are both -CH 3; Z is selected from -CH- and -N-; R 4 is selected from H, -C 1-8 alkyl, -C 1-3 alkylene-O-C 1-8 alkyl, -C 1-3 alkylene-C 6-10 aryl, -C 1-3 alkylene-O-C 6-10 aryl, -C 1-3 alkylene-C 1-9 heteroaryl, -C 3-7 cycloalkyl, -[(CH 2) 2 O] 1-3 CH 3, -C 1-6 alkylene-OC R 40, -C 1-6 alkylene-NR 41 R 42, -C 1-6 alkylene-C R 43, -C 0-6 alkylenemorpholinyl, -C 1-6 alkylene-SO 2 -C 1-6 alkyl, R 40 is selected from -C 1-6 alkyl, -O-C 1-6 alkyl, -C 3-7 cycloalkyl, -O-C 3-7 cycloalkyl, phenyl, -O-phenyl, -NR 41 R 42, -CH(R 45)-NH 2, -CH(R 45)-NHC O-C 1-6 alkyl, and -CH(NH 2)CH 2 COOCH 3; and R 41 and R 42 are independently selected from H, -C 1-6 alkyl, and benzyl; or R 41 and R 42 are taken together as -(CH 2) 3-6 -, -C -(CH 2) 3 -, or -(CH 2) 2 O(CH 2) 2 -; R 43 is selected from -O-C 1-6 alkyl, -O-benzyl, and -NR 41 R 42; and R 44 is -C 1-6 alkyl or -C 0-6 alkylene-C 6-10 aryl; R 45 is H, -CH 3, -CH(CH 3) 2, phenyl, or benzyl; a is 0 or 1; R 5 is selected from halo, -CH 3, -CF 3, and -CN; b is 0 or an integer from 1 to 3; each R 6 is independently selected from halo, -OH, -CH 3, -OCH 3, -CN, and -CF 3; where each alkyl group in R 1 and R 4 is optionally substituted with 1 to 8 fluoro atoms; and where the methylene linker on the biphenyl is optionally substituted with one or two -C 1-6 alkyl groups or cyclopropyl;