A compound of formula 1: wherein: R 1 is H, (C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, (C 1 -C 6)alkanoyl, (C 1 -C 6)alkoxycarbonyl, (C 1 -C 6)alkanoyloxy, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, halo(C 1 -C 6)alkyl, aryl, aryl(C 1 -C 6)alkyl, aryl(C 1 -C 6)alkoxy, aryl(C 1 -C 6)alkanoyl, het, het(C 1 -C 6)alkyl, het(C 1 -C 6)alkoxy, or het(C 1 -C 6)alkanoyl; W is O, S, or two hydrogens; X is O or N-Y-R 4; Y is a direct bond, -CH2-, -C(=O)-, -C(=S)-, -O-. -C(=O)O-, -OC(=O), -C(=O)NR a -,-S-, -S(=O)-, -S(=O) 2 -, or SC(=O) 2 NR a -; R 4 is H, (C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, (C 1 -C 6)alkanoyl, hydroxy, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, halo(C 1 -C 6)alkyl, hydroxy(C 1 -C 6)alkyl, (C 1 -C 6)alkoxycarbonyl, carboxy, aryl, aryl(C 1 -C 6)alkyl, het, NR d R e, -C(=O)NR d R e, NR d R e (C 1 -C 6)alkyl, or het(C 1 -C 6)alkyl; R a is H, (C 1 -C 6)alkyl, (C 3 -C 8)cycloalkyl, (C 1 -C 6)alkoxy(C 2 -C 6)alkyl, or (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl; wherein Z is wherein R 2 is (C 1 -C 6)alkyl, or halo(C 1 -C 6)alkyl; R 3 is (C 3 -C 8)cycloalkyl; or Z is selected from a structure of formula III, IV, and V: that is optionally substituted with one or more substituents selected from (C 1 -C 6)alkyl, halo(C 1 -C 6)alkyl, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, halo(C 2 -C 6)alkoxy, (C 3 -C 8)cycloalkyloxy, and (C 3 -C 8)cycloalkyl(C 1 -C 6)alkoxy; wherein p is 1, 2, 3, 4, 5 or 6; each R d and R e is independently H, hydroxy, (C 1 -C 6)alkyl, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyloxy, (C 2 -C 6)alkynyloxy, (C 1 -C 6)alkanoyl, (C 1 -C 6)alkoxycarbonyl, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, aryl, aryl(C 1 -C 6)alkyl, NR f R g, or aryl(C 1 -C 6)alkoxy; and each R f and Rg is independently H, (C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, (C 1 -C 6)alkanoyl, (C 1 -C 6)alkoxycarbonyl, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, aryl, aryl(C 1 -C 6)alkyl, oraryl(C 1 -C 6)alkoxy; or R f and Rg together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, morpholino, or thiomorpholino ring; wherein any aryl or het of R 1 or R 4 is optionally substituted with one or more substituents independently selected from (C 1 -C 6)alkyl, phenyl, (C 1 -C 6)alkoxy, (C 1 -C 6)alkanoyl, (C 1 -C 6)alkoxycarbonyl, (C 1 -C 6)alkanoyloxy, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, halo(C 1 -C 6)alkyl, (C 3 -C 8)cycloalkyloxy, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkoxy, halo(C 2 -C 6)alkoxy, cyano, nitro, halo, carboxy or NR d R e; and wherein the ring containing X is optionally substituted on carbon with one or more halo, (C 1 -C 6)alkyl, or (C 1 -C 6)alkoxy or a pharmaceutically acceptable salt thereof. R 1 is H, (C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, (C 1 -C 6)alkanoyl, (C 1 -C 6)alkoxycarbonyl, (C 1 -C 6)alkanoyloxy, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, halo(C 1 -C 6)alkyl, aryl, aryl(C 1 -C 6)alkyl, aryl(C 1 -C 6)alkoxy, aryl(C 1 -C 6)alkanoyl, het, het(C 1 -C 6)alkyl, het(C 1 -C 6)alkoxy, or het(C 1 -C 6)alkanoyl; W is O, S, or two hydrogens; X is O or N-Y-R 4; Y is a direct bond, -CH2-, -C(=O)-, -C(=S)-, -O-. -C(=O)O-, -OC(=O), -C(=O)NR a -,-S-, -S(=O)-, -S(=O) 2 -, or SC(=O) 2 NR a -; R 4 is H, (C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, (C 1 -C 6)alkanoyl, hydroxy, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, halo(C 1 -C 6)alkyl, hydroxy(C 1 -C 6)alkyl, (C 1 -C 6)alkoxycarbonyl, carboxy, aryl, aryl(C 1 -C 6)alkyl, het, NR d R e, -C(=O)NR d R e, NR d R e (C 1 -C 6)alkyl, or het(C 1 -C 6)alkyl; R a is H, (C 1 -C 6)alkyl, (C 3 -C 8)cycloalkyl, (C 1 -C 6)alkoxy(C 2 -C 6)alkyl, or (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl; wherein Z is wherein R 2 is (C 1 -C 6)alkyl, or halo(C 1 -C 6)alkyl; R 3 is (C 3 -C 8)cycloalkyl; or Z is selected from a structure of formula III, IV, and V: that is optionally substituted with one or more substituents selected from (C 1 -C 6)alkyl, halo(C 1 -C 6)alkyl, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, halo(C 2 -C 6)alkoxy, (C 3 -C 8)cycloalkyloxy, and (C 3 -C 8)cycloalkyl(C 1 -C 6)alkoxy; wherein p is 1, 2, 3, 4, 5 or 6; each R d and R e is independently H, hydroxy, (C 1 -C 6)alkyl, (C 2 -C 6)alkenyl, (C 2 -C 6)alkynyl, (C 1 -C 6)alkoxy, (C 2 -C 6)alkenyloxy, (C 2 -C 6)alkynyloxy, (C 1 -C 6)alkanoyl, (C 1 -C 6)alkoxycarbonyl, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, aryl, aryl(C 1 -C 6)alkyl, NR f R g, or aryl(C 1 -C 6)alkoxy; and each R f and Rg is independently H, (C 1 -C 6)alkyl, (C 1 -C 6)alkoxy, (C 1 -C 6)alkanoyl, (C 1 -C 6)alkoxycarbonyl, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, aryl, aryl(C 1 -C 6)alkyl, oraryl(C 1 -C 6)alkoxy; or R f and Rg together with the nitrogen to which they are attached form a pyrrolidino, piperidino, piperazino, morpholino, or thiomorpholino ring; wherein any aryl or het of R 1 or R 4 is optionally substituted with one or more substituents independently selected from (C 1 -C 6)alkyl, phenyl, (C 1 -C 6)alkoxy, (C 1 -C 6)alkanoyl, (C 1 -C 6)alkoxycarbonyl, (C 1 -C 6)alkanoyloxy, (C 3 -C 8)cycloalkyl, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkyl, halo(C 1 -C 6)alkyl, (C 3 -C 8)cycloalkyloxy, (C 3 -C 8)cycloalkyl(C 1 -C 6)alkoxy, halo(C 2 -C 6)alkoxy, cyano, nitro, halo, carboxy or NR d R e; and wherein the ring containing X is optionally substituted on carbon with one or more halo, (C 1 -C 6)alkyl, or (C 1 -C 6)alkoxy or a pharmaceutically acceptable salt thereof.