A chemical entity of Formula: wherein X is -CH 2 - or -O-; Y is -CH 2 - or -CF 2 -; Z is -CH 2 - or -C(=O)-; R 1 is a member selected from the group consisting of: (a) phenyl unsubstituted or substituted with one, two, three, four, or five R a members; where R a is each independently selected from the group consisting of: -H, -halo, -C 1-6 alkyl, -C 1-6 haloalkyl, -C 1-6 alkoxy, -C 1-6 haloalkoxy, -CN, -N(C 1-6 alkyl) 2, -SF 5, -C 3-6 cycloalkyl, -pyrrolidine, -morpholine, -piperidine, -pyrazole, -furan, -imidazole, -thiophene, -thiazole, -pyridine, and -phenyl, wherein phenyl is unsubstituted or substituted with one, two, three, four, or five R b members; where R b is each independently selected from the group consisting of: -H, -Cl and -F; or optionally two adjacent R a members come together to form a ring, each optionally unsubstituted or substituted with one or more members independently selected from: -H, -halo, -C 1-6 alkyl, or -C 1-6 alkoxy; (b) monocyclic or bicyclic heteroaromatic ring each unsubstituted or substituted with one, two, three, or four R c members; where each R c is independently selected from the group consisting of: -H, -halo, -C 1-6 alkyl, -C 1-4 haloalkyl, -C 1-4 alkoxy, -N(C 1-6 alkyl) 2, -(C 1-6 alkyl)cycloalkyl, -cyclopropyl, -morpholine, -pyrrolidine, -4-chlorophenoxy, and -phenyl optionally unsubstituted or substituted with -halo, -C 1-6 alkyl, or -C 1-4 alkoxy; and (c) heterocycloalkyl ring unsubstituted or substituted with one or more -H, -F, or -OCH 3; and R 2 is -C 1-6 alkyl; wherein alkyl groups may be optionally substituted with one or more substituents selected from hydroxyl, alkoxy, thioalkoxy, amino, and aminoalkyl; wherein "cycloalkyl" refers to a saturated or partially saturated carbocycle, and "heterocycloalkyl" refers to a monocyclic, or fused, bridged, or spiro polycyclic ring structure that is saturated or partially saturated and has from 3 to 12 ring atoms per ring structure selected from carbon atoms and up to three heteroatoms selected from nitrogen, oxygen, and sulfur; and wherein the chemical entity is a compound of Formula, or a pharmaceutically acceptable salt of a compound of Formula. X is -CH 2 - or -O-; Y is -CH 2 - or -CF 2 -; Z is -CH 2 - or -C(=O)-; R 1 is a member selected from the group consisting of: (a) phenyl unsubstituted or substituted with one, two, three, four, or five R a members; where R a is each independently selected from the group consisting of: -H, -halo, -C 1-6 alkyl, -C 1-6 haloalkyl, -C 1-6 alkoxy, -C 1-6 haloalkoxy, -CN, -N(C 1-6 alkyl) 2, -SF 5, -C 3-6 cycloalkyl, -pyrrolidine, -morpholine, -piperidine, -pyrazole, -furan, -imidazole, -thiophene, -thiazole, -pyridine, and -phenyl, wherein phenyl is unsubstituted or substituted with one, two, three, four, or five R b members; where R b is each independently selected from the group consisting of: -H, -Cl and -F; or optionally two adjacent R a members come together to form a ring, each optionally unsubstituted or substituted with one or more members independently selected from: -H, -halo, -C 1-6 alkyl, or -C 1-6 alkoxy; (b) monocyclic or bicyclic heteroaromatic ring each unsubstituted or substituted with one, two, three, or four R c members; where each R c is independently selected from the group consisting of: -H, -halo, -C 1-6 alkyl, -C 1-4 haloalkyl, -C 1-4 alkoxy, -N(C 1-6 alkyl) 2, -(C 1-6 alkyl)cycloalkyl, -cyclopropyl, -morpholine, -pyrrolidine, -4-chlorophenoxy, and -phenyl optionally unsubstituted or substituted with -halo, -C 1-6 alkyl, or -C 1-4 alkoxy; and (a) phenyl unsubstituted or substituted with one, two, three, four, or five R a members; where R a is each independently selected from the group consisting of: -H, -halo, -C 1-6 alkyl, -C 1-6 haloalkyl, -C 1-6 alkoxy, -C 1-6 haloalkoxy, -CN, -N(C 1-6 alkyl) 2, -SF 5, -C 3-6 cycloalkyl, -pyrrolidine, -morpholine, -piperidine, -pyrazole, -furan, -imidazole, -thiophene, -thiazole, -pyridine, and -phenyl, wherein phenyl is unsubstituted or substituted with one, two, three, four, or five R b members; where R b is each independently selected from the group consisting of: -H, -Cl and -F; or optionally two adjacent R a members come together to form a ring, each optionally unsubstituted or substituted with one or more members independently selected from: -H, -halo, -C 1-6 alkyl, or -C 1-6 alkoxy; (b) monocyclic or bicyclic heteroaromatic ring each unsubstituted or substituted with one, two, three, or four R c members; where each R c is independently selected from the group consisting of: -H, -halo, -C 1-6 alkyl, -C 1-4 haloalkyl, -C 1-4 alkoxy, -N(C 1-6 alkyl) 2, -(C 1-6 alkyl)cycloalkyl, -cyclopropyl, -morpholine, -pyrrolidine, -4-chlorophenoxy, and -phenyl optionally unsubstituted or substituted with -halo, -C 1-6 alkyl, or -C 1-4 alkoxy; and (c) heterocycloalkyl ring unsubstituted or substituted with one or more -H, -F, or -OCH 3; and R 2 is -C 1-6 alkyl; wherein alkyl groups may be optionally substituted with one or more substituents selected from hydroxyl, alkoxy, thioalkoxy, amino, and aminoalkyl;