IP Library › Patent Application 18666159

Patent Application

App. No. 18/666,159

BENZOPIPERAZINE AND RELATED ANALOGS FOR INHIBITING YAP/TAZ-TEAD

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US None
App. No.: 18/666,159

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present disclosure relates to novel compounds, to said compounds for use as a medicine, more in particular for the prevention or treatment of diseases mediated by activity of YAP/TAZ-TEAD transcription, yet more in particular for the prevention or treatment of cancer or fibrosis. The present disclosure also relates to a method for the prevention or treatment of said diseases comprising the use of the novel compounds.

Claims (1256)

1 . A compound of Formula I:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

Z is selected from —O—, —N—, —S—, —S(O)— or —S(O) 2 —,

with the proviso that: when Z is —O—, —S—, —S(O)— or —S(O) 2 —, R 3 is absent;

X 1 and X 2 are independently selected from the group consisting of:

(i) hydrogen,

(ii) halogen,

(iii) hydroxyl,

(iv) cyano,

(v) C 1 -C 6 alkyl,

(vi) C 1 -C 6 haloalkyl,

(vii) C 2 -C 6 alkenyl, and

(viii) carbonyl, or

X 1 and X 2 are taken together with the carbon atoms they are bound to form an:

(i) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

i. halogen,

ii. cyano,

iii. C 1 -C 6 alkyl,

iv. C 3 -C 6 cycloalkyl,

v. C 1 -C 6 haloalkyl, and

vi. —OZ 1 ,

vii. —N(Z 1 ) 2 , and

viii. —C(O)N(Z 1 ) 2 ,

(ii) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O and one or more substituents are independently selected from the group consisting of:

i. halogen,

ii. cyano,

iii. C 1 -C 6 alkyl,

iv. C 3 -C 6 cycloalkyl,

v. C 1 -C 6 haloalkyl, and

vi. —OZ 1 ,

vii. —N(Z 1 ) 2 , and

viii. —C(O)N(Z 1 ) 2 ,

(iii) unsubstituted or substituted C 6 -C 10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

i. halogen,

ii. cyano,

iii. C 1 -C 6 alkyl,

iv. C 3 -C 6 cycloalkyl,

v. C 1 -C 6 haloalkyl, and

vi. —OZ 1 ,

vii. —N(Z 1 ) 2 , and

viii. —C(O)N(Z 1 ) 2 , or

(iv) unsubstituted or substituted 5- to 9-membered heteroaryl, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

i. halogen,

ii. cyano,

iii. C 1 -C 6 alkyl,

iv. C 3 -C 6 cycloalkyl,

v. C 1 -C 6 haloalkyl, and

vi. —OZ 1 ,

vii. —N(Z 1 ) 2 , and

viii. —C(O)N(Z 1 ) 2 ,

with the provisos that:

(i) represents a double bond when X 1 and X 2 are taken together to form an aryl or heteroaryl, and

(ii) represents a single bond when X 1 and X 2 are otherwise

R 1 is selected from the group consisting of:

(i) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

(a) unsubstituted or substituted C 6 -C 10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

(1) halogen,

(2) cyano,

(3) C 1 -C 6 alkyl,

(4) C 3 -C 6 cycloalkyl,

(5) C 1 -C 6 haloalkyl,

(6) —OZ 1 ,

(7) C 2 -C 6 alkenyl, and

(8) C 2 -C 6 alkynyl,

(b) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

(1) halogen,

(2) cyano,

(3) C 1 -C 6 alkyl,

(4) C 3 -C 6 cycloalkyl,

(5) C 1 -C 6 haloalkyl, and

(6) —OZ 1 ,

(d) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, C 2 -C 8 alkenyl, and C 1 -C 6 alkyl,

(ii) unsubstituted or substituted C 6 -C 10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) cyano,

(d) C 3 -C 6 cycloalkyl,

(e) C 1 -C 6 haloalkyl,

(f) —OZ 1 , and

(g) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl, and —OZ 1 ,

(iii) unsubstituted or substituted 5- to 9-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) cyano,

(d) C 3 -C 6 cycloalkyl,

(e) C 1 -C 6 haloalkyl,

(f) —OZ 1 , and

(iv) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) cyano,

(d) C 3 -C 6 cycloalkyl,

(e) C 1 -C 6 haloalkyl, and

(f) —OZ 1 ,

(v) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) cyano,

(d) C 3 -C 6 cycloalkyl,

(e) C 1 -C 6 haloalkyl, and

(f) —OZ 1 ,

(vi) —S(═O) 2 Z 2 , and

(vii) —C(═O)Z 2 ;

R 2 and R 3 are independently selected from the group consisting of:

(i) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

a. cyano,

b. C 1 -C 6 alkyl,

c. —S(═O) 2 Z 5 ,

d. C 3 -C 8 cycloalkyl,

e. —C(═O)OH,

f. —C(═O)Z 1 ,

g. —NZ 3 Z 4 ,

h. halogen,

i. hydroxy,

j. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,

k. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and

l. unsubstituted or substituted C 6 -C 10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 haloalkyl, and cyano,

(ii) unsubstituted or substituted 3- to 6-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

a. halogen,

b. cyano,

c. C 1 -C 6 alkyl,

d. C 3 -C 6 cycloalkyl,

e. C 1 -C 6 haloalkyl,

f. —OZ 1 , and

g. —C(═O)Z 1 ,

(iii) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

a. halogen,

b. cyano,

c. C 1 -C 6 alkyl,

d. C 3 -C 6 cycloalkyl,

e. C 1 -C 6 haloalkyl,

f. —OZ 1 , and

g. —C(═O)Z 1 ,

(iv) hydrogen,

(v) —C(═O)Z 1 , and

(vi) —S(═O) 2 Z 5 , or

R 2 and R 3 are taken together with the carbon and nitrogen atom they are respectively bound to form an:

(i) unsubstituted or substituted 3- to 6-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) cyano,

(c) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

(1) cyano,

(2) C 3 -C 8 cycloalkyl,

(3) —C(═O)OH,

(4) —S(═O) 2 Z 1 ,

(5) —NZ 3 Z 4 ,

(6) halogen, and

(7) unsubstituted or substituted C 3 -C 6 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

a. halogen,

b. cyano,

c. hydroxy,

d. C 1 -C 6 alkyl,

e. C 3 -C 6 cycloalkyl,

f. C 1 -C 6 haloalkyl,

g. —OZ 1 ,

h. —C(═O)Z 1 , and

i. S(═O) 2 Z 5 ,

(d) C 3 -C 6 cycloalkyl,

(e) C 1 -C 6 haloalkyl,

(f) —OZ 1 ,

(g) —C(═O)Z 1 ,

(h) —S(═O) 2 Z 1 ,

(i) unsubstituted or substituted C 3 -C 6 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

(1) halogen,

(2) cyano,

(3) hydroxy,

(4) C 1 -C 6 alkyl,

(5) C 3 -C 6 cycloalkyl,

(6) C 1 -C 6 haloalkyl,

(7) —OZ 1 ,

(8) —C(═O)Z 1 , and

(9) S(═O) 2 Z 5 , and

(j) unsubstituted or substituted 3- to 6-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

(1) halogen,

(2) cyano,

(3) C 1 -C 6 alkyl,

(4) C 3 -C 6 cycloalkyl,

(5) C 1 -C 6 haloalkyl,

(6) —OZ 1 ,

(7) —C(═O)Z 1 , and

(8) S(═O) 2 Z 5 ;

each Z 1 is independently selected from the group consisting of:

(i) hydrogen,

(ii) hydroxyl,

(iii) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

a. cyano,

b. C 1 -C 6 alkyl,

c. —S(═O) 2 Z 5 ,

d. C 3 -C 8 cycloalkyl,

e. —C(═O)OH,

f. —NZ 3 Z 4 ,

g. halogen,

h. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,

i. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and

j. unsubstituted or substituted C 6 -C 10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 haloalkyl, and cyano,

(iv) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of:

a. cyano,

b. —S(═O) 2 Z 5 ,

c. halogen, and

d. unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

i. cyano,

ii. —S(═O) 2 Z 5 ,

iii. C 3 -C 8 cycloalkyl,

iv. —C(═O)OH,

v. —NZ 3 Z 4 ,

vi. halogen,

vii. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 Alkyl, and C 2 -C 6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,

viii. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and

ix. unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 haloalkyl, cyano, —S(═O) 2 Z 5 , —NZ 3 Z 4 and unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 Alkyl, and C 2 -C 6 alkenyl, and zero or more of the aryl carbons can be oxidized to form a C═O,

(v) C 2 -C 6 alkynyl,

(vi) C 3 -C 6 cycloalkyl,

(vii) C 3 -C 6 cycloalkenyl,

(viii) C 1 -C 6 haloalkyl,

(ix) —OZ 2 ,

(x) —C(═O)Z 2 ,

(xi) —NHZ 2 ,

(xii) unsubstituted or substituted C 3 -C 8 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O) 2 Z 5 , —NZ 3 Z 4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,

(xiii) unsubstituted or substituted C 6 -C 10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O) 2 Z 5 , —NZ 3 Z 4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,

(xiv) unsubstituted or substituted 3- to 8-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl, and

(xv) unsubstituted or substituted 3- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl;

each Z 2 is independently selected from the group consisting of:

(i) C 1 -C 6 alkyl,

(ii) —NHZ 3 ,

(iii) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 5 , halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 5 , —NZ 3 Z 4 and 4- to 8-membered heterocycle,

(iv) C 2 -C 6 alkynyl,

(v) C 3 -C 6 cycloalkyl,

(vi) C 3 -C 6 cycloalkenyl,

(vii) C 1 -C 6 haloalkyl, and

(viii) hydrogen;

each Z 3 is independently selected from the group consisting of:

(i) hydrogen,

(iv) —C(═O)Z 7 ,

(v) C 2 -C 6 alkynyl,

(vi) C 3 -C 6 cycloalkyl,

(vii) C 3 -C 6 cycloalkenyl, and

(viii) C 1 -C 6 haloalkyl;

each Z 4 is independently selected from the group consisting of:

(i) hydrogen,

(ii) C 1 -C 6 alkyl, and

(iii) C 3 -C 6 cycloalkyl;

each Z 5 is independently selected from the group consisting of:

(i) hydrogen,

(ii) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, and C 1 -C 6 alkyl,

(iii) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of —NZ 6 Z 4 and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,

(iv) halogen, and

(v) hydroxy;

each Z 6 is independently selected from the group consisting of:

(i) hydrogen,

(ii) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of C 2 -C 6 alkenyl, cyano, —C(═O)OH, —S(═O) 2 H, —S(═O) 2 (unsubstituted or substituted C 1 -C 6 alkyl), —S(═O) 2 (unsubstituted or substituted C 2 -C 6 alkenyl), —S(═O) 2 (halogen), —S(═O) 2 OH, —NHZ 4 , —N(unsubstituted or substituted C 1 -C 6 alkyl)Z 4 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)Z 4 , —N(—C(═O)Z 7 )Z 4 , —N(C 2 -C 6 alkynyl)Z 4 , —N(C 3 -C 6 cycloalkyl)Z 4 , —N(C 3 -C 6 cycloalkenyl)Z 4 , —N(C 1 -C 6 haloalkyl)Z 4 , and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,

(iii) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 H, —S(═O) 2 (unsubstituted or substituted C 1 -C 6 alkyl), —S(═O) 2 (unsubstituted or substituted C 2 —C 6 alkenyl), —S(═O) 2 (halogen), —S(═O) 2 OH, halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 5 , —NHZ 4 , —N(unsubstituted or substituted C 1 -C 6 alkyl)Z 4 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)Z 4 , —N(—C(═O)Z 7 )Z 4 , —N(C 2 -C 6 alkynyl)Z 4 , —N(C 3 -C 6 cycloalkyl)Z 4 , —N(C 3 -C 6 cycloalkenyl)Z 4 , —N(C 1 -C 6 haloalkyl)Z 4 , and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,

(iv) —C(═O)Z 7 ,

(v) C 2 -C 6 alkynyl,

(vi) C 3 -C 6 cycloalkyl,

(vii) C 3 -C 6 cycloalkenyl, and

(viii) C 1 -C 6 haloalkyl; and

each Z 7 is independently selected from the group consisting of:

(i) hydrogen,

(ii) hydroxyl,

(iii) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

a. cyano,

b. C 1 -C 6 alkyl,

c. —S(═O) 2 Z 9 ,

d. C 3 -C 8 cycloalkyl,

e. —C(═O)OH,

f. —NHZ 8 ,

g. —N(unsubstituted or substituted C 1 -C 6 alkyl)Z 8 ,

h. —N(unsubstituted or substituted C 2 -C 6 alkenyl)Z 8 ,

i. —N(—C(═O) unsubstituted or substituted C 3 -C 6 cycloalkyl)Z 8 ,

j. —N(—C(═O) unsubstituted or substituted C 3 -C 6 cycloalkenyl)Z 8 ,

k. —N(—C(═O) unsubstituted or substituted C 1 -C 6 haloalkyl)Z 8 ,

l. —N(C 2 -C 6 alkynyl)Z 8 ,

m. —N(C 3 -C 6 cycloalkyl)Z 8 ,

n. —N(C 3 -C 6 cycloalkenyl)Z 8 ,

o. —N(C 1 -C 6 haloalkyl)Z 8 ,

p. halogen,

q. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,

r. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and

s. unsubstituted or substituted C 6 -C 10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 haloalkyl, and cyano,

(iv) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of:

a. cyano,

b. —S(═O) 2 Z 9 ,

c. halogen, and

(v) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

a. cyano,

b. —S(═O) 2 Z 9 ,

c. C 3 -C 8 cycloalkyl,

d. —C(═O)OH,

(vi) —NHZ 8 ,

(vii) —N(unsubstituted or substituted C 1 -C 6 alkyl)Z 8 ,

(viii) —N(unsubstituted or substituted C 2 -C 6 alkenyl)Z 8 ,

(ix) —N(unsubstituted or substituted C 2 -C 6 alkynyl)Z 8 ,

(x) —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)Z 8 ,

(xi) —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)Z 8 ,

(xii) —N(C 1 -C 6 haloalkyl)Z 8 ,

(xiii) halogen,

(xiv) unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 akyl, and C 2 -C 6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,

(xv) unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 Alkyl, and C 2 -C 6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and

(xvi) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 haloalkyl, cyano, —S(═O) 2 Z 9 , —NZ 6 Z 8 and unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl, and zero or more of the aryl carbons can be oxidized to form a C═O,

(xvii) C 2 -C 6 alkynyl,

(xviii) C 3 -C 6 cycloalkyl,

(xix) C 3 -C 6 cycloalkenyl,

(xx) C 1 -C 6 haloalkyl,

(xxi) —OZ 10 ,

(xxii) —C(═O)Z 10 ,

(xxiii) —NHZ 10 ,

(xxiv) unsubstituted or substituted C 3 -C 8 cycloalkyl, wherein zero or more of the cycloalkyl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O) 2 Z 5 , —NZ 3 Z 4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,

(xxv) unsubstituted or substituted C 6 -C 10 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, cyano, and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —S(═O) 2 Z 5 , —NZ 3 Z 4 and 4- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O,

(xxvi) unsubstituted or substituted 3- to 8-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl,

(xxvii) unsubstituted or substituted 3- to 8-membered heterocycle, wherein zero or more of the heterocycle carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 alkyl, and C 2 -C 6 alkenyl; and

each Z 8 is independently selected from the group consisting of:

(i) hydrogen,

(ii) C 1 -C 6 alkyl, and

(iii) C 3 -C 6 cycloalkyl;

each Z 9 is independently selected from the group consisting of:

(i) hydrogen,

(ii) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, and C 1 -C 6 alkyl,

(iv) halogen, and

(v) hydroxy; and

each Z 10 is independently selected from the group consisting of:

(i) C 1 -C 6 alkyl,

(ii) —NH 2 ,

(iii) —NH(C 1 -C 6 alkyl),

(iv) —N(C 1 -C 6 alkyl) 2 ,

(v) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 5 , halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 5 , —NZ 3 Z 4 and 4- to 8-membered heterocycle,

(vi) C 2 -C 6 alkynyl,

(vii) C 3 -C 6 cycloalkyl,

(viii) C 3 -C 6 cycloalkenyl,

(ix) C 1 -C 6 haloalkyl, and

(x) hydrogen.

2 . The compound of claim 1 of Formula II:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

Z′ and Z″ are independently selected from —CH═ or —N═.

3 . The compound of claim 2 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z′ and Z″ are —CH═.

4 . The compound of claim 2 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z′ is —N═ and Z″ is —CH═.

5 . The compound of claim 2 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z′ and Z″ are —N═.

6 . The compound of claim 2 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z is —O—.

7 . The compound of claim 2 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z is —N—.

8 . The compound of claim 1 of Formula III:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

R′ is selected from the group consisting of:

i. hydrogen,

ii. halogen,

iii. cyano,

iv. unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

a) cyano,

b) C 3 -C 8 cycloalkyl,

c) —C(═O)OH,

d) —S(═O) 2 Z 1 ,

e) —NZ 3 Z 4 ,

f) halogen, and

g) unsubstituted or substituted C 3 -C 6 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

1. halogen,

2. cyano,

3. hydroxy,

4. C 1 -C 6 alkyl,

5. C 3 -C 6 cycloalkyl,

6. C 1 -C 6 haloalkyl,

7. —OZ 1 ,

8. —C(═O)Z 1 , and

9. S(═O) 2 Z 5 ,

v. C 3 -C 6 cycloalkyl,

vi. C 1 -C 6 haloalkyl,

vii. —OZ 1 ,

viii. —C(═O)Z 1 ,

ix. —S(═O) 2 Z 1 ,

x. unsubstituted or substituted C 3 -C 6 aryl, wherein zero or more of the aryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

a) halogen,

b) cyano,

c) hydroxy,

d) C 1 -C 6 alkyl,

e) C 3 -C 6 cycloalkyl,

f) C 1 -C 6 haloalkyl,

g) —OZ 1 ,

h) —C(═O)Z 1 , and

i) S(═O) 2 Z 5 , and

xi. unsubstituted or substituted 3- to 6-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

a) halogen,

b) cyano,

c) C 1 -C 6 alkyl,

d) C 3 -C 6 cycloalkyl,

e) C 1 -C 6 haloalkyl,

f) —OZ 1 ,

g) —C(═O)Z 1 , and

h) S(═O) 2 Z 5 .

9 . The compound of claim 8 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is —C(═O)Z 1 .

10 . The compound of claim 8 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is —S(═O) 2 Z 1 .

11 . The compound of claim 8 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is unsubstituted or substituted 3- to 6-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

a) halogen,

b) cyano,

c) C 1 -C 6 alkyl,

d) C 3 -C 6 cycloalkyl,

e) C 1 -C 6 haloalkyl,

f) —OZ 1 ,

g) —C(═O)Z 1 , and

h) S(═O) 2 Z 5 .

12 . The compound of claim 1 of Formula IV:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

Z′ and Z″ are independently selected from —CH═ or —N═;

R′ is selected from the group consisting of:

i. hydrogen,

ii. halogen,

iii. cyano,

iv. unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

a) cyano,

b) C 3 -C 8 cycloalkyl,

c) —C(═O)OH,

d) —S(═O) 2 Z 1 ,

e) —NZ 3 Z 4 ,

f) halogen, and

1. halogen,

2. cyano,

3. hydroxy,

4. C 1 -C 6 alkyl,

5. C 3 -C 6 cycloalkyl,

6. C 1 -C 6 haloalkyl,

7. —OZ 1 ,

8. —C(═O)Z 1 , and

9. S(═O) 2 Z 5 ,

v. C 3 -C 6 cycloalkyl,

vi. C 1 -C 6 haloalkyl,

vii. —OZ 1 ,

viii. —C(═O)Z,

ix. —S(═O) 2 Z 1 ,

a) halogen,

b) cyano,

c) hydroxy,

d) C 1 -C 6 alkyl,

e) C 3 -C 6 cycloalkyl,

f) C 1 -C 6 haloalkyl,

g) —OZ 1 ,

h) —C(═O)Z 1 , and

i) S(═O) 2 Z 5 , and

a) halogen,

b) cyano,

c) C 1 -C 6 alkyl,

d) C 3 -C 6 cycloalkyl,

e) C 1 -C 6 haloalkyl,

f) —OZ 1 ,

g) —C(═O)Z 1 , and

h) S(═O) 2 Z 5 .

13 . The compound of claim 12 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z′ and Z″ are —CH═.

14 . The compound of claim 12 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z′ is —N═ and Z″ is —CH═.

15 . The compound of claim 12 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z′ and Z″ are —N═.

16 . The compound of claim 12 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is —C(═O)Z 1 .

17 . The compound of claim 12 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is —S(═O) 2 Z 1 .

18 . The compound of claim 12 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is unsubstituted or substituted 3- to 6-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

a) halogen,

b) cyano,

c) C 1 -C 6 alkyl,

d) C 3 -C 6 cycloalkyl,

e) C 1 -C 6 haloalkyl,

f) —OZ 1 ,

g) —C(═O)Z 1 , and

h) S(═O) 2 Z 5 .

19 . The compound of claim 1 of Formula V:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

Z′ and Z″ are independently selected from —CH═ or —N═;

each of Q 1 , Q 2 , Q 3 , and Q 4 are independently ═N— or ═CH—.

20 . The compound of claim 19 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z′ and Z″ are —CH═.

21 . The compound of claim 19 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z′ is —N═ and Z″ is —CH═.

22 . The compound of claim 19 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z′ and Z″ are —N═.

23 . The compound of claim 19 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z is —O—.

24 . The compound of claim 19 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z is —N—.

25 . The compound of claim 19 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , Q 3 , and Q 4 are ═CH—.

26 . The compound of claim 19 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , and Q 4 are ═CH— and Q 3 is ═N—.

27 . The compound of claim 19 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , and Q 3 are ═CH— and Q 4 is ═N—.

28 . The compound of claim 1 of Formula VI:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

R′ is selected from the group consisting of:

i. hydrogen,

ii. halogen,

iii. cyano,

iv. unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

a) cyano,

b) C 3 -C 8 cycloalkyl,

c) —C(═O)OH,

d) —S(═O) 2 Z 1 ,

e) —NZ 3 Z 4 ,

f) halogen, and

1. halogen,

2. cyano,

3. hydroxy,

4. C 1 -C 6 alkyl,

5. C 3 -C 6 cycloalkyl,

6. C 1 -C 6 haloalkyl,

7. —OZ 1 ,

8. —C(═O)Z 1 , and

9. S(═O) 2 Z 5 ,

V. C 3 -C 6 cycloalkyl,

vi. C 1 -C 6 haloalkyl,

vii. —OZ 1 ,

viii. —C(═O)Z 1 ,

ix. —S(═O) 2 Z 1 ,

a) halogen,

b) cyano,

c) hydroxy,

d) C 1 -C 6 alkyl,

e) C 3 -C 6 cycloalkyl,

f) C 1 -C 6 haloalkyl,

g) —OZ 1 ,

h) —C(═O)Z 1 , and

i) S(═O) 2 Z 5 , and

a) halogen,

b) cyano,

c) C 1 -C 6 alkyl,

d) C 3 -C 6 cycloalkyl,

e) C 1 -C 6 haloalkyl,

f) —OZ 1 ,

g) —C(═O)Z 1 , and

h) S(═O) 2 Z 5 ;

each of Q 1 , Q 2 , Q 3 , and Q 4 are independently ═N— or ═CH—.

29 . The compound of claim 28 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is —C(═O)Z 1 .

30 . The compound of claim 28 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is —S(═O) 2 Z 1 .

31 . The compound of claim 28 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is unsubstituted or substituted 3- to 6-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

a) halogen,

b) cyano,

c) C 1 -C 6 alkyl,

d) C 3 -C 6 cycloalkyl,

e) C 1 -C 6 haloalkyl,

f) —OZ 1 ,

g) —C(═O)Z 1 , and

h) S(═O) 2 Z 5 .

32 . The compound of claim 28 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , Q 3 , and Q 4 are ═CH—.

33 . The compound of claim 28 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , and Q 4 are ═CH— and Q 3 is ═N—.

34 . The compound of claim 28 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , and Q 3 are ═CH— and Q 4 is ═N—.

35 . The compound of claim 1 of Formula VII:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

Z′ and Z″ are independently selected from —CH═ or —N═;

R′ is selected from the group consisting of:

i. hydrogen,

ii. halogen,

iii. cyano,

iv. unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

a) cyano,

b) C 3 -C 8 cycloalkyl,

c) —C(═O)OH,

d) —S(═O) 2 Z 1 ,

e) —NZ 3 Z 4 ,

f) halogen, and

1. halogen,

2. cyano,

3. hydroxy,

4. C 1 -C 6 alkyl,

5. C 3 -C 6 cycloalkyl,

6. C 1 -C 6 haloalkyl,

7. —OZ 1 ,

8. —C(═O)Z 1 , and

9. S(═O) 2 Z 5 ,

v. C 3 -C 6 cycloalkyl,

vi. C 1 -C 6 haloalkyl,

vii. —OZ 1 ,

viii. —C(═O)Z 1 ,

ix. —S(═O) 2 Z 1 ,

a) halogen,

b) cyano,

c) hydroxy,

d) C 1 -C 6 alkyl,

e) C 3 -C 6 cycloalkyl,

f) C 1 -C 6 haloalkyl,

g) —OZ 1 ,

h) —C(═O)Z 1 , and

i) S(═O) 2 Z 5 , and

a) halogen,

b) cyano,

c) C 1 -C 6 alkyl,

d) C 3 -C 6 cycloalkyl,

e) C 1 -C 6 haloalkyl,

f) —OZ 1 ,

g) —C(═O)Z 1 , and

h) S(═O) 2 Z 5 ;

each of Q 1 , Q 2 , Q 3 , and Q 4 are independently ═N— or ═CH—.

36 . The compound of claim 35 , or a stereoisomer, tautomer,

pharmaceutically acceptable salt, or solvate thereof, wherein Z′ and Z″ are —CH═.

37 . The compound of claim 35 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z′ is —N═ and Z″ is —CH═.

38 . The compound of claim 35 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z′ and Z″ are —N═.

39 . The compound of claim 35 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is —C(═O)Z 1 .

40 . The compound of claim 35 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is —S(═O) 2 Z 1 .

41 . The compound of claim 35 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R′ is unsubstituted or substituted 3- to 6-membered heteroaryl, wherein zero or more of the heteroaryl carbons can be oxidized to form a C═O, and one or more substituents are independently selected from the group consisting of:

a) halogen,

b) cyano,

c) C 1 -C 6 alkyl,

d) C 3 -C 6 cycloalkyl,

e) C 1 -C 6 haloalkyl,

f) —OZ 1 ,

g) —C(═O)Z 1 , and

h) S(═O) 2 Z 5 .

42 . The compound of claim 35 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , Q 3 , and Q 4 are ═CH—.

43 . The compound of claim 35 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , and Q 4 are ═CH— and Q 3 is ═N—.

44 . The compound of claim 35 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , and Q 3 are ═CH— and Q 4 is ═N—.

45 . A compound of Formula VIII:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

each of Q 1 , Q 2 , Q 3 , and Q 4 are independently ═N— or ═CH—;

Z is selected from —O—, —N—, —S—, —S(O)— or —S(O) 2 —,

with the proviso that: when Z is —O—, —S—, —S(O)— or —S(O) 2 —, R 3 is absent;

X 1 and X 2 are independently selected from the group consisting of:

(i) hydrogen,

(ii) halogen,

(iii) hydroxyl,

(iv) cyano,

(v) C 1 -C 6 alkyl,

(vi) C 1 -C 6 haloalkyl,

(vii) C 2 -C 6 alkenyl, and

(viii) carbonyl, or

X 1 and X 2 are taken together with the carbon atoms they are bound to form an:

i. halogen,

ii. cyano,

iii. C 1 -C 6 alkyl,

iv. C 3 -C 6 cycloalkyl,

v. C 1 -C 6 haloalkyl, and

vi. —OZ 1 ,

vii. —N(Z 1 ) 2 , and

viii. —C(O)N(Z 1 ) 2 ,

i. halogen,

ii. cyano,

iii. C 1 -C 6 alkyl,

iv. C 3 -C 6 cycloalkyl,

v. C 1 -C 6 haloalkyl, and

vi. —OZ 1 ,

vii. —N(Z 1 ) 2 , and

viii. —C(O)N(Z 1 ) 2 ,

i. halogen,

ii. cyano,

iii. C 1 -C 6 alkyl,

iv. C 3 -C 6 cycloalkyl,

v. C 1 -C 6 haloalkyl, and

vi. —OZ 1 ,

vii. —N(Z 1 ) 2 , and

viii. —C(O)N(Z 1 ) 2 , or

i. halogen,

ii. cyano,

iii. C 1 -C 6 alkyl,

iv. C 3 -C 6 cycloalkyl,

v. C 1 -C 6 haloalkyl, and

vi. —OZ 1 ,

vii. —N(Z 1 ) 2 , and

viii. —C(O)N(Z 1 ) 2 ,

with the provisos that:

(i) represents a double bond when X 1 and X 2 are taken together to form an aryl or heteroaryl; and

(ii) represents a single bond when X 1 and X 2 are otherwise;

R 2 and R 3 are independently selected from the group consisting of:

(i) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

a. cyano,

b. C 1 -C 6 alkyl,

c. —S(═O) 2 Z 5 ,

d. C 3 -C 8 cycloalkyl,

e. —C(═O)OH,

f. —C(═O)Z 1 ,

g. —NZ 3 Z 4 ,

h. halogen,

i. hydroxy,

j. unsubstituted or substituted 3- to 8-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 Alkyl, and C 2 -C 6 alkenyl, and zero or more of the heterocycle carbons can be oxidized to form a C═O,

k. unsubstituted or substituted 3- to 9-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of halogen, C 1 -C 6 Alkyl, and C 2 -C 6 alkenyl, and zero or more of the heteroaryl carbons can be oxidized to form a C═O, and

a. halogen,

b. cyano,

c. C 1 -C 6 alkyl,

d. C 3 -C 6 cycloalkyl,

e. C 1 -C 6 haloalkyl,

f. —OZ 1 , and

g. —C(═O)Z 1 ,

a. halogen,

b. cyano,

c. C 1 -C 6 alkyl,

d. C 3 -C 6 cycloalkyl,

e. C 1 -C 6 haloalkyl,

f. —OZ 1 , and

g. —C(═O)Z 1 ,

(iv) hydrogen,

(v) —C(═O)Z 1 , and

(vi) —S(═O) 2 Z 5 , or

R 2 and R 3 are taken together with the carbon and nitrogen atom they are respectively bound to form an:

(a) halogen,

(b) cyano,

(c) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

(1) cyano,

(2) C 3 -C 8 cycloalkyl,

(3) —C(═O)OH,

(4) —S(═O) 2 Z 1 ,

(5) —NZ 3 Z 4 , and

(6) halogen,

(d) C 3 -C 6 cycloalkyl,

(e) C 1 -C 6 haloalkyl,

(f) —OZ 1 ,

(g) —C(═O)Z 1 ,

(h) —S(═O) 2 Z 1 ,

(1) halogen,

(2) cyano,

(3) hydroxy,

(4) C 1 -C 6 alkyl,

(5) C 3 -C 6 cycloalkyl,

(6) C 1 -C 6 haloalkyl,

(7) —OZ 1 ,

(8) —C(═O)Z 1 , and

(9) S(═O) 2 Z 5 , and

(1) halogen,

(2) cyano,

(3) C 1 -C 6 alkyl,

(4) C 3 -C 6 cycloalkyl,

(5) C 1 -C 6 haloalkyl,

(6) —OZ 1 ,

(7) —C(═O)Z 1 , and

(8) S(═O) 2 Z 5 ;

each Z 1 is independently selected from the group consisting of:

(i) hydrogen,

(ii) hydroxyl,

(iii) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

a. cyano,

b. C 1 -C 6 alkyl,

c. —S(═O) 2 Z 5 ,

d. C 3 -C 8 cycloalkyl,

e. —C(═O)OH,

f. —NZ 3 Z 4 ,

g. halogen,

(iv) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of:

a. cyano,

b. —S(═O) 2 Z 5 ,

c. halogen, and

d. unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

i. cyano,

ii. —S(═O) 2 Z 5 ,

iii. C 3 -C 8 cycloalkyl,

iv. —C(═O)OH,

v. —NZ 3 Z 4 ,

vi. halogen,

(v) C 2 -C 6 alkynyl,

(vi) C 3 -C 6 cycloalkyl,

(vii) C 3 -C 6 cycloalkenyl,

(viii) C 1 -C 6 haloalkyl,

(ix) —OZ 2 ,

(x) —C(═O)Z 2 ,

(xi) —NHZ 2 ,

each Z 2 is independently selected from the group consisting of:

(i) C 1 -C 6 alkyl,

(ii) —NHZ 3 ,

(iv) C 2 -C 6 alkynyl,

(v) C 3 -C 6 cycloalkyl,

(vi) C 3 -C 6 cycloalkenyl,

(vii) C 1 -C 6 haloalkyl, and

(viii) hydrogen;

each Z 3 is independently selected from the group consisting of:

(i) hydrogen,

(iv) —C(═O)Z 7 ,

(v) C 2 -C 6 alkynyl,

(vi) C 3 -C 6 cycloalkyl,

(vii) C 3 -C 6 cycloalkenyl, and

(viii) C 1 -C 6 haloalkyl;

each Z 4 is independently selected from the group consisting of:

(i) hydrogen,

(ii) C 1 -C 6 alkyl, and

(iii) C 3 -C 6 cycloalkyl;

each Z 5 is independently selected from the group consisting of:

(i) hydrogen,

(ii) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, and C 1 -C 6 alkyl,

(iv) halogen, and

(v) hydroxy;

each Z 6 is independently selected from the group consisting of:

(i) hydrogen,

(iii) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 H, —S(═O) 2 (unsubstituted or substituted C 1 -C 6 alkyl), —S(═O) 2 (unsubstituted or substituted C 2 -C 6 alkenyl), —S(═O) 2 (halogen), —S(═O) 2 OH, halogen and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of cyano, —S(═O) 2 Z 5 , —NHZ 4 , —N(unsubstituted or substituted C 1 -C 6 alkyl)Z 4 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)Z 4 , —N(—C(═O)Z 7 )Z 4 , —N(C 2 -C 6 alkynyl)Z 4 , —N(C 3 -C 6 cycloalkyl)Z 4 , —N(C 3 -C 6 cycloalkenyl)Z 4 , —N(C 1 -C 6 haloalkyl)Z 4 , and 4- to 8-membered heterocycle wherein, zero or more of the heterocycle carbons can be oxidized to form a C═O,

(iv) —C(═O)Z 7 ,

(v) C 2 -C 6 alkynyl,

(vi) C 3 -C 6 cycloalkyl,

(vii) C 3 -C 6 cycloalkenyl, and

(viii) C 1 -C 6 haloalkyl;

each Z 7 is independently selected from the group consisting of:

(i) hydrogen,

(ii) hydroxyl,

(iii) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

a. cyano,

b. C 1 -C 6 alkyl,

c. —S(═O) 2 Z 9 ,

d. C 3 -C 8 cycloalkyl,

e. —C(═O)OH,

f. —NHZ 8 ,

g. —N(unsubstituted or substituted C 1 -C 6 alkyl)Z 8 ,

h. —N(unsubstituted or substituted C 2 -C 6 alkenyl)Z 8 ,

i. —N(—C(═O) unsubstituted or substituted C 3 -C 6 cycloalkyl)Z 8 ,

j. —N(—C(═O) unsubstituted or substituted C 3 -C 6 cycloalkenyl)Z 8 ,

k. —N(—C(═O) unsubstituted or substituted C 1 -C 6 haloalkyl)Z 8 ,

l. —N(C 2 -C 6 alkynyl)Z 8 ,

m. —N(C 3 -C 6 cycloalkyl)Z 8 ,

n. —N(C 3 -C 6 cycloalkenyl)Z 8 ,

o. —N(C 1 -C 6 haloalkyl)Z 8 ,

p. halogen,

(iv) unsubstituted or substituted C 2 -C 6 alkenyl, wherein one or more substituents are independently selected from the group consisting of:

a. cyano,

b. —S(═O) 2 Z 9 ,

c. halogen, and

(v) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

e. cyano,

f. —S(═O) 2 Z 9 ,

g. C 3 -C 8 cycloalkyl,

h. —C(═O)OH,

(vi) —NHZ 8 ,

(vii) —N(unsubstituted or substituted C 1 -C 6 alkyl)Z 8 ,

(viii) —N(unsubstituted or substituted C 2 -C 6 alkenyl)Z 8 ,

(ix) —N(unsubstituted or substituted C 2 -C 6 alkynyl)Z 8 ,

(x) —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)Z 8 ,

(xi) —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)Z 8 ,

(xii) —N(C 1 -C 6 haloalkyl)Z 8 ,

(xiii) halogen,

(xvii) C 2 -C 6 alkynyl,

(xviii) C 3 -C 6 cycloalkyl,

(xix) C 3 -C 6 cycloalkenyl,

(xx) C 1 -C 6 haloalkyl,

(xxi) —OZ 10 ,

(xxii) —C(═O)Z 10 ,

(xxiii) —NHZ 10 ,

each Z 8 is independently selected from the group consisting of:

(i) hydrogen,

(ii) C 1 -C 6 alkyl, and

(iii) C 3 -C 6 cycloalkyl;

each Z 9 is independently selected from the group consisting of:

(i) hydrogen,

(ii) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, and C 1 -C 6 alkyl,

(iv) halogen, and

(v) hydroxy; and

each Z 10 is independently selected from the group consisting of:

(i) C 1 -C 6 alkyl,

(ii) —NH 2 ,

(iii) —NH(C 1 -C 6 alkyl),

(iv) —N(C 1 -C 6 alkyl) 2 ,

(vi) C 2 -C 6 alkynyl,

(vii) C 3 -C 6 cycloalkyl,

(viii) C 3 -C 6 cycloalkenyl,

(ix) C 1 -C 6 haloalkyl, and

(x) hydrogen.

46 . The compound of claim 45 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , Q 3 , and Q 4 are ═CH—.

47 . The compound of claim 45 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , and Q 4 are ═CH— and Q 3 is ═N—.

48 . The compound of claim 45 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 1 , Q 2 , and Q 3 are ═CH— and Q 4 is ═N—.

49 . The compound of claim 19 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z is —O—.

50 . The compound of claim 19 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Z is —N—.

51 . A compound of Formula IX:

or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

each of Q 1 , Q 2 , Q 3 , and Q 4 are independently ═N— or ═CH—;

each of Q 5 , Q 6 , Q 7 , and Q 8 are independently ═N— or ═CR—, wherein each R is, individually, H or C 1 -C 6 alkyl;

L is —O— or —NR 2 , wherein R 2 is H or C 1 -C 6 alkyl (e.g., Me);

each of R a , R b , R c , R d , R e , R f , R g and R h are independently H or C 1 -C 6 alkyl (e.g., Me), or one or more of R a and R b , R c and R d , R e and R f , and/or R g and R h , together with the carbon atom to which they are attached, for a carbonyl (—C(═O)) group; and

R 1 is H or C 1 -C 6 alkyl.

52 . The compound of claim 51 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein L is —O—, —NH— or —NMe-.

53 . The compound of claim 51 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein each of Q 1 , Q 2 , Q 3 , and Q 4 is ═CH—.

54 . The compound of claim 51 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein each of Q 5 , Q 6 , Q 7 and Q 1 is ═CH—.

55 . The compound of claim 51 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein Q 5 is ═N— and each of Q 6 , Q 7 and Q 1 are ═CR—.

56 . The compound of claim 51 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein R 1 is H.

57 . The compound of claim 51 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein each of R a , R b , R c , R f , R g and R h are H and R c and R d , together with the carbon atom to which they are attached, form a carbonyl (—C(═O)) group.

58 . compound of claim 1 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, selected from the group consisting of:

N-((1-(2-hydroxyethyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

N-((1-(2-hydroxyethyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acetamide;

N-((1-(cyanomethyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

N-((1-(cyanomethyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acetamide;

N-((1-(3-hydroxypropyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

N-((1-(3-hydroxypropyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acetamide;

3-(2-(acrylamidomethyl)-4-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinoxalin-1(2H)-yl)propanoic acid;

3-(2-(acetamidomethyl)-4-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinoxalin-1(2H)-yl)propanoic acid;

N-((1-(3-(methylamino)-3-oxopropyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

6-(4-(trifluoromethyl)phenyl)-4,4a,5,6-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-2(3H)-one;

N-((1-(2-amino-2-oxoethyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

N-((1-(2-(methylamino)-2-oxoethyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

N-((1-(3-amino-3-oxopropyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

1-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)prop-2-en-1-one;

(R)- or (S)-1-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)prop-2-en-1-one;

1-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)ethan-1-one;

(R)- or (S)-1-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)ethan-1-one;

3-(methylsulfonyl)-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline;

N-((1-methyl-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

(R)- or (S)—N-((1-methyl-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

N-((1-acetyl-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

N-((1-methyl-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acetamide;

Methyl 6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxaline-3-carboxylate;

1-(8-(4-(trifluoromethyl)phenyl)octahydro-2H-pyrazino[1,2-a]pyrazin-2-yl)prop-2-en-1-one;

N-((4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

(R)- or (S)—N-((4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

N-((1-(methylsulfonyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

2-methyl-5-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)-1,3,4-oxadiazole;

2-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)oxazole;

3-methyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline;

N-((4-methyl-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acrylamide;

(R)- or (S)—N-((4-methyl-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acrylamide;

(R)- or (S)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)prop-2-en-1-one;

(R)- or (S)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;

2-hydroxy-4-((6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)methyl)benzaldehyde;

2-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)acetic acid;

N-methyl-6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxaline-3-sulfonamide;

(R)- or (S)—N-methyl-6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxaline-3-sulfonamide;

8-acryloyl-2-(4-(trifluoromethyl)phenyl)hexahydro-2H-pyrazino[1,2-a]pyrazin-3(4H)-one;

N-((4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acetamide;

(R)- or (S)—N-((4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acetamide;

N-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methyl)acrylamide;

(R)- or (S)—N-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methyl)acrylamide;

N-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methyl)acetamide;

(R)- or (S)—N-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methyl)acetamide;

8-acryloyl-2-(4-(trifluoromethyl)phenyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one;

(R)- or (S)-8-acryloyl-2-(4-(trifluoromethyl)phenyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one;

(S)—N-((1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acrylamide;

(R)—N-((1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acrylamide;

(S)—N-((1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acetamide;

(R)—N-((1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acetamide;

1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-dipyrazino[1,2-a:2′,3′-e]pyrazin-8-yl)ethan-1-one;

(R)- or (S)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-dipyrazino[1,2-a:2′,3′-e]pyrazin-8-yl)ethan-1-one;

1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-dipyrazino[1,2-a:2′,3′-e]pyrazin-8-yl)prop-2-en-1-one;

(R)- or (S)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-dipyrazino[1,2-a:2′,3′-e]pyrazin-8-yl)prop-2-en-1-one;

1-(3-(4-(trifluoromethyl)phenyl)decahydro-6H-cyclobuta[e]pyrazino[1,2-a]pyrazin-6-yl)prop-2-en-1-one (diastereomer 1);

1-(3-(4-(trifluoromethyl)phenyl)decahydro-6H-cyclobuta[e]pyrazino[1,2-a]pyrazin-6-yl)prop-2-en-1-one (diastereomer 2);

1-(1,1-dichloro-2-(4-(trifluoromethyl)phenyl)octahydrocyclopropa[e]pyrazino[1,2-a]pyrazin-5(1H)-yl)prop-2-en-1-one;

8-acetyl-2-(4-(trifluoromethyl)phenyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one;

N-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazine-8-sulfonamide;

(R)- or (S)—N-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazine-8-sulfonamide;

cyclopropyl(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)methanone;

2-methyl-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)propan-1-one;

(R)- or (S)-2-methyl-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)propan-1-one;

N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acrylamide;

N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

1-((4H-1,2,4-triazol-3-yl)methyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxaline;

1-((1H-imidazol-5-yl)methyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxaline;

N-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazine-8-carboxamide;

1-(5-(5-(trifluoromethyl)pyridin-2-yl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;

1-(5-(6-(trifluoromethyl)pyridin-3-yl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;

(6aR,8S)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl methylcarbamate;

1-(3-(4-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinoxalin-1(2H)-yl)azetidin-1-yl)ethan-1-one; and

N-(2-(4-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinoxalin-1(2H)-yl)ethyl)acetamide.

59 . The compound of claim 1 , or a tautomer, pharmaceutically acceptable salt, or solvate thereof, selected from the group consisting of:

1-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)prop-2-en-1-one;

(R)-1-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)prop-2-en-1-one;

(S)-1-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)prop-2-en-1-one;

1-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)ethan-1-one;

(R)-1-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)ethan-1-one;

(S)-1-(6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxalin-3-yl)ethan-1-one;

N-((1-methyl-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

(R)—N-((1-methyl-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

(S)—N-((1-methyl-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

N-((4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

(R)—N-((4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

(S)—N-((4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acrylamide;

N-((4-methyl-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acrylamide;

(R)—N-((4-methyl-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acrylamide;

(S)—N-((4-methyl-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acrylamide;

1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)prop-2-en-1-one;

(R)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)prop-2-en-1-one;

(S)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)prop-2-en-1-one;

1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;

(R)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;

(S)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;

N-methyl-6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxaline-3-sulfonamide;

(R)—N-methyl-6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxaline-3-sulfonamide;

(S)—N-methyl-6-(4-(trifluoromethyl)phenyl)-1,2,4,4a,5,6-hexahydro-3H-pyrazino[1,2-a]quinoxaline-3-sulfonamide;

N-((4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acetamide;

(R)—N-((4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acetamide;

(S)—N-((4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxalin-2-yl)methyl)acetamide;

N-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methyl)acrylamide;

(R)—N-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methyl)acrylamide;

(S)—N-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methyl)acrylamide;

N-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methyl)acetamide;

(R)—N-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methyl)acetamide;

(S)—N-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)methyl)acetamide;

8-acryloyl-2-(4-(trifluoromethyl)phenyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one;

(R)-8-acryloyl-2-(4-(trifluoromethyl)phenyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one;

(S)-8-acryloyl-2-(4-(trifluoromethyl)phenyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one;

N-((1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acrylamide;

(R)—N-((1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acrylamide;

(S)—N-((1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acrylamide;

N-((1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acetamide;

(R)—N-((1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acetamide;

(S)—N-((1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-3-yl)methyl)acetamide;

1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-dipyrazino[1,2-a:2′,3′-e]pyrazin-8-yl)ethan-1-one;

(R)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-dipyrazino[1,2-a:2′,3′-e]pyrazin-8-yl)ethan-1-one;

(S)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-dipyrazino[1,2-a:2′,3′-e]pyrazin-8-yl)ethan-1-one;

1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-dipyrazino[1,2-a:2′,3′-e]pyrazin-8-yl)prop-2-en-1-one;

(R)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-dipyrazino[1,2-a:2′,3′-e]pyrazin-8-yl)prop-2-en-1-one;

(S)-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-dipyrazino[1,2-a:2′,3′-e]pyrazin-8-yl)prop-2-en-1-one;

1-(3-(4-(trifluoromethyl)phenyl)decahydro-6H-cyclobuta[e]pyrazino[1,2-a]pyrazin-6-yl)prop-2-en-1-one;

1-(3-(4-(trifluoromethyl)phenyl)decahydro-6H-cyclobuta[e]pyrazino[1,2-a]pyrazin-6-yl)prop-2-en-1-one (diastereomer 1);

1-(3-(4-(trifluoromethyl)phenyl)decahydro-6H-cyclobuta[e]pyrazino[1,2-a]pyrazin-6-yl)prop-2-en-1-one (diastereomer 2);

N-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazine-8-sulfonamide;

(R)—N-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazine-8-sulfonamide;

(S)—N-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazine-8-sulfonamide;

2-methyl-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)propan-1-one;

(R)-2-methyl-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)propan-1-one;

(S)-2-methyl-1-(5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)propan-1-one; and

(6aR,8S)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl methylcarbamate.

60 . The compound of claim 1 , or a tautomer, pharmaceutically acceptable salt, or solvate thereof, selected from the group consisting of:

(R)- or (S)—N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acrylamide;

(R)- or (S)—N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)- or (S)—N-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazine-8-carboxamide;

(R)- or (S)-1-(5-(5-(trifluoromethyl)pyridin-2-yl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;

N-((4,4-dioxido-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-3-yl)methyl)acetamide;

8-acetyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8-tetrahydroimidazo[1,5-a]pyrido[3,2-e]pyrazin-9(5H)-one;

1-((1-methyl-1H-imidazol-5-yl)methyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxaline;

1-((2-methyl-1H-imidazol-5-yl)methyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxaline;

1-((1H-imidazol-2-yl)methyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxaline;

1-((1H-pyrazol-4-yl)methyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxaline;

1-(pyridin-3-ylmethyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxaline;

(cis)- or (trans)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

1-((4-methyl-1H-imidazol-5-yl)methyl)-4-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoxaline;

5-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinoxalin-1(2H)-yl)methyl)oxazole;

5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydropyrido[3′,2′:5,6]pyrazino[2,1-c][1,4]thiazine 8,8-dioxide;

5-((4-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinoxalin-1(2H)-yl)methyl)isoxazole;

N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)acetamide;

N-((6aR,8S)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)acetamide;

8-(methylsulfonyl)-2-(4-(trifluoromethyl)phenyl)octahydro-4H-pyrazino[1,2-a]pyrazin-4-one;

N-methyl-6-oxo-8-(4-(trifluoromethyl)phenyl)octahydro-2H-pyrazino[1,2-a]pyrazine-2-sulfonamide;

(6aS,8S)— or (6aR,8S)— or (6aR,8R)— or (6aS,8R)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

N-((6-methoxy-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(1H-pyrazol-4-yl)(4-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinoxalin-1(2H)-yl)methanone;

N-((7-chloro-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

N-((6-(trifluoromethyl)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

N-((6-methyl-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)- or (S)—N-((6-methyl-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)- or (S)—N-((7-chloro-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)- or (S)—N-((6-methoxy-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

N-((1-(5-(trifluoromethyl)pyridin-2-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

3-acetyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxalin-1-one;

1-((1H-pyrazol-4-yl)methyl)-4-(4-(trifluoromethyl)phenyl)-3,4-dihydroquinoxalin-2(1H)-one;

(R)- or (S)-3-acetyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxalin-1-one;

N-((6-cyclopropyl-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

N-((6-ethyl-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

methyl ((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)carbamate;

1-methyl-3-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)urea;

N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)methanesulfonamide;

N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl),N′-methylsulfuric diamide;

N-((6-(dimethylamino)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(cis)- or (trans)-3-acryloyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline-2-carboxylic acid;

(cis)- or (trans)-3-acetyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline-2-carboxylic acid;

(6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl methylcarbamate;

N-((6aR,8R)-3-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)acetamide;

(R)- or (S)—N-((6-cyclopropyl-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)- or (S)—N-((6-(dimethylamino)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

3-oxo-3-(((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)amino)propanoic acid;

2-hydroxy-N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)acetamide;

(cis)- or (trans)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

2-amino-N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)acetamide;

N-((6aR,8R)-3-chloro-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)acetamide;

(R)- or (S)—N-((6-cyano-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)- or (S)-3-(acetamidomethyl)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-6-carboxamide;

(cis)- or (trans)-3-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(6aS,8S)— or (6aR,8S)— or (6aR,8R)— or (6aS,8R)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(6aS,8S)— or (6aR,8S)— or (6aR,8R)— or (6aS,8R)-2-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazine-8-carboxylic acid;

(6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazine-8-carbonitrile;

(cis)- or (trans)-3-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(cis)- or (trans)-1-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(cis)- or (trans)-2-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

N-((6aR,8R)-2-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)acetamide;

N-((6-(difluoromethoxy)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)-2-hydroxy-N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)propanamide;

(S)-2-hydroxy-N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)propanamide;

2-hydroxy-2-methyl-N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)propanamide;

N-((6-(difluoromethyl)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(6aR,8S)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazine-8-carboxylic acid;

(cis)- or (trans)-8-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aS,8S)— or (6aR,8S)— or (6aR,8R)— or (6aS,8R)-8-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(cis)- or (trans)-N-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(cis)- or (trans)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(6aS,8S)— or (6aR,8S)— or (6aR,8R)— or (6aS,8R)-8-(1H-tetrazol-5-yl)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline;

(R)- or (S)—N-((6-bromo-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(6aS,8S)— or (6aR,8S)— or (6aR,8R)— or (6aS,8R)-8-fluoro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aS,8S)— or (6aR,8S)— or (6aR,8R)— or (6aS,8R)—N-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(6aS,8S)— or (6aR,8S)— or (6aR,8R)— or (6aS,8R)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide; and

(cis)- or (trans)-8-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid.

61 . The compound of claim 1 , or a tautomer, pharmaceutically acceptable salt, or solvate thereof, selected from the group consisting of:

N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acrylamide;

(R)—N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acrylamide;

(S)—N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acrylamide;

N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)—N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(S)—N-((1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

N-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazine-8-carboxamide;

(R)—N-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazine-8-carboxamide;

(S)—N-methyl-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazine-8-carboxamide;

1-(5-(5-(trifluoromethyl)pyridin-2-yl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;

(R)-1-(5-(5-(trifluoromethyl)pyridin-2-yl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;

(S)-1-(5-(5-(trifluoromethyl)pyridin-2-yl)-5,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrido[3,2-e]pyrazin-8-yl)ethan-1-one;

5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(cis)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(trans)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aS,8S)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aR,8S)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aR,8R)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aS,8R)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

N-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)acetamide;

N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)acetamide;

N-((6aR,8S)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)acetamide;

N-((6-methoxy-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)—N-((6-methoxy-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(S)—N-((6-methoxy-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

N-((7-chloro-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)—N-((7-chloro-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)—(S)—N-((7-chloro-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

N-((6-methyl-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)—N-((6-methyl-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(S)—N-((6-methyl-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

3-acetyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxalin-1-one;

(R)-3-acetyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxalin-1-one;

(S)-3-acetyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxalin-1-one;

N-((6-cyclopropyl-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)—N-((6-cyclopropyl-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(S)—N-((6-cyclopropyl-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

N-((6-(dimethylamino)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)—N-((6-(dimethylamino)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(S)—N-((6-(dimethylamino)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

3-acryloyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline-2-carboxylic acid;

(cis)-3-acryloyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline-2-carboxylic acid;

(trans)-3-acryloyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline-2-carboxylic acid;

3-acetyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline-2-carboxylic acid;

(cis)-3-acetyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline-2-carboxylic acid;

(trans)-3-acetyl-6-(4-(trifluoromethyl)phenyl)-2,3,4,4a,5,6-hexahydro-1H-pyrazino[1,2-a]quinoxaline-2-carboxylic acid;

5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(cis)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(trans)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(6aS,8S)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(6aR,8S)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(6aR,8R)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(6aS,8R)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

N-((6-cyano-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)—N-((6-cyano-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(S)—N-((6-cyano-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

3-(acetamidomethyl)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-6-carboxamide;

(R)-3-(acetamidomethyl)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-6-carboxamide;

(S)-3-(acetamidomethyl)-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-6-carboxamide;

3-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(cis)-3-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(trans)-3-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

2-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(6aS,8S)-2-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(6aR,8S)-2-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(6aR,8R)-2-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

(6aS,8R)-2-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-dipyrido[1,2-a:3′,2′-e]pyrazine-8-carboxylic acid;

3-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(cis)-3-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(trans)-3-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

1-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(cis)-1-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(trans)-1-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

2-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(cis)-2-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(trans)-2-chloro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

2-hydroxy-N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)propanamide;

(R)-2-hydroxy-N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)propanamide;

(S)-2-hydroxy-N-((6aR,8R)-5-(4-(trifluoromethyl)phenyl)-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-8-yl)propanamide;

8-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(cis)-8-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(trans)-8-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

8-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aS,8S)-8-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aR,8S)-8-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aR,8R)-8-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aS,8R)-8-methyl-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

N-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(cis)-N-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(trans)-N-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(cis)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(trans)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

8-(1H-tetrazol-5-yl)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline;

(6aS,8S)-8-(1H-tetrazol-5-yl)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline;

(6aR,8S)-8-(1H-tetrazol-5-yl)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline;

(6aR,8R)-8-(1H-tetrazol-5-yl)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline;

(6aS,8R)-8-(1H-tetrazol-5-yl)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline;

N-((6-bromo-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(R)—N-((6-bromo-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

(S)—N-((6-bromo-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-3-yl)methyl)acetamide;

8-fluoro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aS,8S)-8-fluoro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aR,8S)-8-fluoro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aR,8R)-8-fluoro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(6aS,8R)-8-fluoro-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

N-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(6aS,8S)—N-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(6aR,8S)—N-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(6aR,8R)—N-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(6aS,8R)—N-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(6aS,8S)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(6aR,8S)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(6aR,8R)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

(6aS,8R)-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxamide;

8-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid;

(cis)-8-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid; and

(trans)-8-hydroxy-5-(4-(trifluoromethyl)phenyl)-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-8-carboxylic acid.

62 . compound of claim 51 , or a tautomer, pharmaceutically acceptable salt, or solvate thereof, selected from the group consisting of:

1-(2-((4-(trifluoromethyl)phenyl)amino)phenyl)piperidine-4-carboxylic acid;

1-(2-(methyl(4-(trifluoromethyl)phenyl)amino)phenyl)piperidine-4-carboxylic acid;

2-oxo-1-(2-((4-(trifluoromethyl)phenyl)amino)phenyl)piperidine-4-carboxylic acid;

1-(2-(4-(trifluoromethyl)phenoxy)phenyl)piperidine-4-carboxylic acid;

1-(3-((4-(trifluoromethyl)phenyl)amino)pyridin-2-yl)piperidine-4-carboxylic acid; and

1-(6-methyl-3-((4-(trifluoromethyl)phenyl)amino)pyridin-2-yl)piperidine-4-carboxylic acid.

63 . A compound or a tautomer, pharmaceutically acceptable salt, or solvate thereof, selected from the group consisting of: