IP Library › Patent Application 18665995

Patent Application

App. No. 18/665,995

BENZIMIDAZOLE AND RELATED ANALOGS FOR INHIBITING YAP/TAZ-TEAD

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App. No.: 18/665,995

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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. The present disclosure furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds as well as to said compositions or preparations for use as a medicine, more preferably 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 processes for the preparation of said compounds.

Claims (575)

1 . A compound of Formula I:

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

X 1 is selected from the group consisting of C and N;

X 2 is selected from the group consisting of C and N;

X 3 is selected from the group consisting of —CR 3 ═, —CR 4 ═, and —N═;

X 4 is selected from the group consisting of —CR 3 ═, —CR 4 ═, and —N═;

R 1 is selected from the group consisting of:

(i) hydrogen

(ii) —(CH 2 ) n —NZ 2 Z 3 ,

(iii) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) C 1 -C 6 alkyl,

(d) cyano,

(e) —C(═O)NZ 2 Z 3 ,

(f) —OZ 1 ,

(g) —NZ 2 Z 3 ,

(h) —C(═O)OZ 4 ,

(i) —C(═O)Z 4 ,

(j) —S(═O)Z 4 , and

(k) —S(═O)NZ 2 Z 3 ,

(iv) unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) cyano,

(d) —SZ 1 ,

(e) —NZ 2 Z 3 ,

(f) —C(═O)Z 4 ,

(g) —C(═O)OZ 4 ,

(h) —C(═O)NZ 2 Z 3 ,

(i) —NZ 5 C(═O)Z 4 ,

(j) —NZ 5 C(═O)OZ 4 ,

(k) —NZ 5 C(═O)NZ 2 Z 3 ,

(l) —S(═O) 2 Z 8 ,

(m) —S(═O) 2 NZ 2 Z 3 ,

(n) —S(═O)(═NZ 6 )Z 4 ,

(o) —S(═Z 6 )(═NZ 7 )Z 4 ,

(p) —S(═O)(═NZ 6 )NZ 2 Z 3 ,

(q) —NZ 5 S(═O) 2 Z 4 ,

(r) —NZ 5 S(═O) 2 NZ 2 Z 3 ,

(s) —NZ 5 S(═O)(═NZ 6 )Z 4 ,

(t) —NZ 5 S(═NZ 6 )(═NZ 7 )Z 4 ,

(u) —NZ 5 S(═O)(═NZ 6 )NZ 2 Z 3 ,

(v) C 1 -C 6 alkyl,

(w)C 1 -C 6 haloalkyl, and

(x) C 3 -C 6 cycloalkyl,

(v) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) —OZ 1 ,

(d) cyano,

(e) —C(═O)Z 1 ,

(f) —C(═O)OZ 4 ,

(g) C 1 -C 6 haloalkyl,

(vi) unsubstituted or substituted 5- to 10-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) unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of:

i. halogen,

ii. cyano,

iii. —OZ 1 ,

iv. —SZ 1 ,

v. —NZ 2 Z 3

vi. —C(═O)Z 4

vii. —C(═O)OZ 4 ,

viii. —C(═O)NZ 2 Z 3 ,

ix. —NZ 5 C(═O)Z 4 ,

x. —NZ 5 C(═O)OZ 4 ,

xi. —NZ 5 C(═O)NZ 2 Z 3 ,

xii. —S(═O) 2 Z 8 ,

xiii. —S(═O) 2 NZ 2 Z 3 ,

xiv. —S(═O)(═NZ 6 )Z 4 ,

xv. —S(═Z 6 )(═NZ 7 )Z 4 ,

xvi. —S(═O)(═NZ 6 )NZ 2 Z 3 ,

xvii. —NZ 5 S(═O) 2 Z 4 ,

xviii. —NZ 5 S(═O) 2 NZ 2 Z 3 ,

xix. —NZ 5 S(═O)(═NZ 6 )Z 4 ,

xx. —NZ 5 S(═NZ 6 )(═NZ 7 )Z 4 ,

xxi. —NZ 5 S(═O)(═NZ 6 )NZ 2 Z 3 ,

xxii. C 1 -C 6 alkyl,

xxiii. C 1 -C 6 haloalkyl,

xxiv. C 3 -C 6 cycloalkyl, and

xxv. 4- to 10-membered heterocycle

(d) C 1 -C 6 haloalkyl,

(e) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of C 1 -C 6 alkyl, halogen, C 1 -C 6 haloalkyl, —OZ, and —NZ 2 Z 3 ,

(f) —C(═O)NZ 2 Z 3 ,

(g) —NZ 2 Z 3 ,

(h) 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 halogen, cyano, —OZ 1 , —SZ 1 , —NZ 2 Z 3 , —C(═O)Z 4 , —C(═O)OZ 4 , —C(═O)NZ 2 Z 3 , —NZ 5 C(═O)Z 4 , —NZ 5 C(═O)OZ 4 , —NZ 5 C(═O)NZ 2 Z 3 ,—S(═O) 2 Z 8 , —S(═O) 2 NZ 2 Z 3 , —S(═O)(═NZ 6 )Z 4 , —S(═Z 6 )(═NZ 7 )Z 4 , —S(═O)(═NZ 6 )NZ 2 Z 3 ,—NZ 5 S(═O) 2 Z 4 , —NZ 5 S(═O) 2 NZ 2 Z 3 , —NZ 5 S(═O)(═NZ 6 )Z 4 , —NZ 5 S(═NZ 6 )(═NZ 7 )Z 4 , —NZ 5 S(═O)(═NZ 6 )NZ 2 Z 3 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, and 4- to 8-membered heterocycle,

(i) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of:

i. halo,

ii. —OZ 1 ,

iii. cyano,

iv. C 1 -C 6 haloalkyl,

v. unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of C 1 -C 6 alkyl, hydroxy, and —NZ 3 Z 4 ,

vi. —C(═O)NZ 3 Z 4 ,

vii. —NZ 3 Z 4 ,

viii. and unsubstituted or substituted C 1 -C 6 alkyl, wherein one or more substituents are independently selected from the group consisting of halogen, cyano, —OZ 1 , —SZ 1 , —NZ 2 Z 3 , —C(═O)Z 4 , —C(═O)OZ 4 , —C(═O)NZ 2 Z 3 , —NZ 5 C(═O)Z 4 , —NZ 5 C(═O)OZ 4 , —NZ 5 C(═O)NZ 2 Z 3 , —S(═O) 2 Z 8 , —S(═O) 2 NZ 2 Z 3 , —S(═O)(═NZ 6 )Z 4 , —S(═Z 6 )(═NZ 7 )Z 4 , —S(═O)(═NZ 6 )NZ 2 Z 3 ,—NZ 5 S(═O) 2 Z 4 , —NZ 5 S(═O) 2 NZ 2 Z 3 , —NZ 5 S(═O)(═NZ 6 )Z 4 , —NZ 5 S(═NZ 6 )(═NZ 7 )Z 4 , —NZ 5 S(═O)(═NZ 6 )NZ 2 Z 3 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, and 4- to 8-membered heterocycle,

ix. 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 halogen, cyano, —OZ 1 , —SZ 1 , —NZ 2 Z 3 , —C(═O)Z 4 , —C(═O)OZ 4 , —C(═O)NZ 2 Z 3 , —NZ 5 C(═O)Z 4 , —NZ 5 C(═O)OZ 4 , —NZ 5 C(═O)NZ 2 Z 3 ,—S(═O) 2 Z 8 , —S(═O) 2 NZ 2 Z 3 , —S(═O)(═NZ 6 )Z 4 , —S(═Z 6 )(═NZ 7 )Z 4 , —S(═O)(═NZ 6 )NZ 2 Z 3 , —NZ 5 S(═O) 2 Z 4 , —NZ 5 S(═O) 2 NZ 2 Z 3 , —NZ 5 S(═O)(═NZ 6 )Z 4 , —NZ 5 S(═NZ 6 )(═NZ 7 )Z 4 , —NZ 5 S(═O)(═NZ 6 )NZ 2 Z 3 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, and 4- to 8-membered heterocycle,

x. unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of halo, —OZ 1 , C 1 -C 6 alkyl, cyano, hydroxy, and C 1 -C 6 haloalkyl,

xi. unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl,

xii. —OZ 1 ,

xiii. —NZ 5 S(═O)Z 4 ,

xiv. —NZ 5 S(═O) 2 Z 4 , and

xv. —NZ 5 S(═O) 2 NZ 2 Z 3 ,

(j) unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of:

i. halogen,

ii. cyano,

iii. —OZ 1 ,

iv. —SZ 1 ,

v. —NZ 2 Z 3

vi. —C(═O)Z 4

vii. —C(═O)OZ 4 ,

viii. —C(═O)NZ 2 Z 3 ,

ix. —NZ 5 C(═O)Z 4 ,

x. —NZ 5 C(═O)OZ 4 ,

xi. —NZ 5 C(═O)NZ 2 Z 3 ,

xii. —S(═O) 2 Z 8 ,

xiii. —S(═O) 2 NZ 2 Z 3 ,

xiv. —S(═O)(═NZ 6 )Z 4 ,

xv. —S(═Z 6 )(═NZ 7 )Z 4 ,

xvi. —S(═O)(═NZ 6 )NZ 2 Z 3 ,

xvii. —NZ 5 S(═O) 2 Z 4 ,

xviii. —NZ 5 S(═O) 2 NZ 2 Z 3 ,

xix. —NZ 5 S(═O)(═NZ 6 )Z 4 ,

xx. —NZ 5 S(═NZ 6 )(═NZ 7 )Z 4 ,

xxi. —NZ 5 S(═O)(═NZ 6 )NZ 2 Z 3 ,

xxii. C 1 -C 6 alkyl,

xxiii. C 1 -C 6 haloalkyl, and

xxiv. C 3 -C 6 cycloalkyl,

xxv. —OZ 1 ,

xxvi. —C(═O)OZ 4 ,

xxvii. —S(═O) 2 Z 1 , and

xxviii. —NZ 5 C(═O)Z 4 ;

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

i. halogen,

ii. cyano,

iii. —OZ 1 ,

iv. —SZ 1 ,

v. —NZ 2 Z 3

vi. —C(═O)Z 4

vii. —C(═O)OZ 4 ,

viii. —C(═O)NZ 2 Z 3 ,

ix. —NZ 5 C(═O)Z 4 ,

x. —NZ 5 C(═O)OZ 4 ,

xi. —NZ 5 C(═O)NZ 2 Z 3 ,

xii. —S(═O) 2 Z 8 ,

xiii. —S(═O) 2 NZ 2 Z 3 ,

xiv. —S(═O)(═NZ 6 )Z 4 ,

xv. —S(═Z 6 )(═NZ 7 )Z 4 ,

xvi. —S(═O)(═NZ 6 )NZ 2 Z 3 ,

xvii. —NZ 5 S(═O) 2 Z 4 ,

xviii. —NZ 5 S(═O) 2 NZ 2 Z 3 ,

xix. —NZ 5 S(═O)(═NZ 6 )Z 4 ,

xx. —NZ 5 S(═NZ 6 )(═NZ 7 )Z 4 ,

xxi. —NZ 5 S(═O)(═NZ 6 )NZ 2 Z 3 ,

xxii. C 1 -C 6 alkyl,

xxiii. C 1 -C 6 haloalkyl,

xxiv. C 3 -C 6 cycloalkyl, and

xxv. 4- to 10-membered heterocycle

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

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

i. halogen,

ii. cyano,

iii. —OZ 1 ,

iv. —SZ 1 ,

v. —NZ 2 Z 3

vi. —C(═O)Z 4

vii. —C(═O)OZ 4 ,

viii. —C(═O)NZ 2 Z 3 ,

ix. —NZ 5 C(═O)Z 4 ,

x. —NZ 5 C(═O)OZ 4 ,

xi. —NZ 5 C(═O)NZ 2 Z 3 ,

xii. —S(═O) 2 Z 8 ,

xiii. —S(═O) 2 NZ 2 Z 3 ,

xiv. —S(═O)(═NZ 6 )Z 4 ,

xv. —S(═Z 6 )(═NZ 7 )Z 4 ,

xvi. —S(═O)(═NZ 6 )NZ 2 Z 3 ,

xvii. —NZ 5 S(═O) 2 Z 4 ,

xviii. —NZ 5 S(═O) 2 NZ 2 Z 3 ,

xix. —NZ 5 S(═O)(═NZ 6 )Z 4 ,

xx. —NZ 5 S(═NZ 6 )(═NZ 7 )Z 4 ,

xxi. —NZ 5 S(═O)(═NZ 6 )NZ 2 Z 3 ,

xxii. C 1 -C 6 alkyl,

xxiii. C 1 -C 6 haloalkyl,

xxiv. C 3 -C 6 cycloalkyl, and

xxv. 4- to 10-membered heterocycle

(b) —NZ 2 Z 3

(d) —C(═O)OZ 4 , and

(e) —S(═O) 2 Z 1 ;

n is 0 or 1;

R 2 is selected from the group consisting of:

(i) —(CH 2 ) n NZ 2 Z 3 ,

(ii) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) —OZ 1 ,

(d) cyano,

(e) C 1 -C 6 alkyl, and

(f) C 1 -C 6 haloalkyl,

(iii) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:

(a) halogen,

(b) C 1 -C 6 alkyl,

(d) cyano,

(e) —C(═O)NZ 2 Z 3 ,

(f) —OZ 1 ,

(g) —NZ 2 Z 3 ,

(h) —C(═O)OZ 4 ,

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

(i) halogen,

(ii) C 1 -C 6 alkyl,

(iii) cyano,

(iv) —C(═O)NZ 2 Z 3 ,

(v) —OZ 1 ,

(vi) —NZ 2 Z 3 ,

(vii) —C(═O)OZ 4 ,

(viii) hydrogen, and

(ix) C 1 -C 6 haloalkyl;

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

(i) halogen,

(ii) C 1 -C 6 alkyl,

(iii) cyano,

(iv) —C(═O)NZ 2 Z 3 ,

(v) —OZ 1 ,

(vi) —NZ 2 Z 3

(vii) —C(═O)OZ 4 ,

(viii) hydrogen, and

(ix) C 1 -C 6 haloalkyl;

each Z 1 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:

a. halogen,

b. cyano,

c. —OZ 9 ,

d. —SZ 9 ,

e. —NZ 2 Z 3 ,

f. —C(═O)Z 4 ,

g. —C(═O)OZ 4 ,

h. —C(═O)NZ 2 Z 3 ,

i. —NZ 5 C(═O)Z 4 ,

j. —NZ 5 C(═O)OZ 4 ,

k. —NZ 5 C(═O)NZ 2 Z 3 ,

l. —S(═O) 2 Z 8 ,

m. —S(═O) 2 NZ 2 Z 3 ,

n. —S(═O)(═NZ 6 )Z 4 ,

o. —S(═Z 6 )(═NZ 7 )Z 4 ,

p. —S(═O)(═NZ 6 )NZ 2 Z 3 ,

q. —NZ 5 S(═O) 2 Z 4 ,

r. —NZ 5 S(═O) 2 NZ 2 Z 3 ,

s. —NZ 5 S(═O)(═NZ 6 )Z 4 ,

t. —NZ 5 S(═NZ 6 )(═NZ 7 )Z 4 ,

u. —NZ 5 S(═O)(═NZ 6 )NZ 2 Z 3 ,

v. C 1 -C 6 alkyl,

w. C 1 -C 6 haloalkyl,

x. C 3 -C 6 cycloalkyl, and

y. 4- to 10-membered heterocycle,

(v) unsubstituted or substituted C 3 -C 6 cycloalkyl, 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 2 Z 3 and 4- to 8-membered heterocycle,

(vi) C 3 -C 6 cycloalkenyl, 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 2 Z 3 and 4- to 8-membered heterocycle,

(vii) C 1 -C 6 haloalkyl, 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 2 Z 3 and 4- to 8-membered heterocycle, and

(viii) —NZ 2 Z 3 ;

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

(i) hydrogen,

(ii) 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 —NH 2 , —NH(unsubstituted or substituted C 2 -C 6 alkenyl), —NH(unsubstituted or substituted C 2 -C 6 alkynyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —NH(unsubstituted or substituted C 1 -C 6 haloalkyl), —NH(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 , —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 , —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl), —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl), N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), and 4- to 8-membered heterocycle,

(iii) unsubstituted or substituted C 2 -C 6 alkynyl, 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 —NH 2 , —NH(unsubstituted or substituted C 2 -C 6 alkenyl), —NH(unsubstituted or substituted C 2 -C 6 alkynyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —NH(unsubstituted or substituted C 1 -C 6 haloalkyl), —NH(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 , —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 , —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl), —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl), N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), and 4- to 8-membered heterocycle,

(iv) unsubstituted or substituted C 3 -C 6 cycloalkyl, 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 —NH 2 , —NH(unsubstituted or substituted C 2 -C 6 alkenyl), —NH(unsubstituted or substituted C 2 -C 6 alkynyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —NH(unsubstituted or substituted C 1 -C 6 haloalkyl), —NH(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 , —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 , —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl), —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl), N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), and 4- to 8-membered heterocycle,

(v) unsubstituted or substituted C 3 -C 6 cycloalkenyl, 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 —NH 2 , —NH(unsubstituted or substituted C 2 -C 6 alkenyl), —NH(unsubstituted or substituted C 2 -C 6 alkynyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —NH(unsubstituted or substituted C 1 -C 6 haloalkyl), —NH(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 , —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 , —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl), —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl), N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), and 4- to 8-membered heterocycle,

(vi) unsubstituted or substituted C 1 -C 6 haloalkyl, 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 —NH 2 , —NH(unsubstituted or substituted C 2 -C 6 alkenyl), —NH(unsubstituted or substituted C 2 -C 6 alkynyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —NH(unsubstituted or substituted C 1 -C 6 haloalkyl), —NH(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 , —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 , —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl), —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl), N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), and 4- to 8-membered heterocycle,

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

(a) —OZ 9 ,

(b) —C(═O)OZ 4 ,

(viii) —S(═O) 2 Z 4 , and

(ix) —(C═O)Z 4 ;

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

(i) hydrogen,

(ii) 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 —NH 2 , —NH(unsubstituted or substituted C 2 -C 6 alkenyl), —NH(unsubstituted or substituted C 2 -C 6 alkynyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —NH(unsubstituted or substituted C 1 -C 6 haloalkyl), —NH(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 , —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 , —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl), —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl), N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), and 4- to 8-membered heterocycle,

(iv) unsubstituted or substituted C 2 -C 6 alkynyl, 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 —NH 2 , —NH(unsubstituted or substituted C 2 -C 6 alkenyl), —NH(unsubstituted or substituted C 2 -C 6 alkynyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —NH(unsubstituted or substituted C 1 -C 6 haloalkyl), —NH(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 , —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 , —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl), —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl), N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), and 4- to 8-membered heterocycle,

(v) unsubstituted or substituted C 2 -C 6 alkynyl, 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 —NH 2 , —NH(unsubstituted or substituted C 2 -C 6 alkenyl), —NH(unsubstituted or substituted C 2 -C 6 alkynyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —NH(unsubstituted or substituted C 1 -C 6 haloalkyl), —NH(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 , —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 , —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl), —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl), N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), and 4- to 8-membered heterocycle,

(vi) unsubstituted or substituted C 3 -C 6 cycloalkyl, 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 —NH 2 , —NH(unsubstituted or substituted C 2 -C 6 alkenyl), —NH(unsubstituted or substituted C 2 -C 6 alkynyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —NH(unsubstituted or substituted C 1 -C 6 haloalkyl), —NH(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 , —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 , —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl), —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl), N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), and 4- to 8-membered heterocycle,

(vii) unsubstituted or substituted C 3 -C 6 cycloalkenyl, 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 —NH 2 , —NH(unsubstituted or substituted C 2 -C 6 alkenyl), —NH(unsubstituted or substituted C 2 -C 6 alkynyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —NH(unsubstituted or substituted C 1 -C 6 haloalkyl), —NH(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 , —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 , —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl), —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl), N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), and 4- to 8-membered heterocycle, and

(viii) unsubstituted or substituted C 1 -C 6 haloalkyl, 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 —NH 2 , —NH(unsubstituted or substituted C 2 -C 6 alkenyl), —NH(unsubstituted or substituted C 2 -C 6 alkynyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl), —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —NH(unsubstituted or substituted C 1 -C 6 haloalkyl), —NH(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 , —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 , —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 , —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 , —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl), —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl), N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl), —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl), —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl), and 4- to 8-membered heterocycle;

each Z 5 , Z 6 and Z 7 -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 8 is independently selected from the group consisting of:

(i) hydrogen,

(ii) C 1 -C 6 alkyl,

(iv) halogen, and

(v) —OZ 9 .

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:

a. halogen,

b. cyano,

c. —OH,

d. —O(unsubstituted or substituted C 1 -C 6 alkyl),

e. —O(unsubstituted or substituted C 2 -C 6 alkenyl),

f. —O(unsubstituted or substituted C 2 -C 6 alkynyl),

g. —O(unsubstituted or substituted C 3 -C 6 cycloalkyl),

h. —O(C 3 -C 6 cycloalkenyl),

i. —O(C 1 -C 6 haloalkyl),

j. —SH,

k. —S(unsubstituted or substituted C 1 -C 6 alkyl),

l. —S(unsubstituted or substituted C 2 -C 6 alkenyl),

m. —S(unsubstituted or substituted C 2 -C 6 alkynyl),

n. —S(unsubstituted or substituted C 3 -C 6 cycloalkyl),

o. —O(C 3 -C 6 cycloalkenyl),

p. —S(C 1 -C 6 haloalkyl),

q. —NH 2 ,

r. —NH(unsubstituted or substituted C 2 -C 6 alkenyl),

s. —NH(unsubstituted or substituted C 2 -C 6 alkynyl),

t. —NH(unsubstituted or substituted C 3 -C 6 cycloalkyl),

u. —NH(unsubstituted or substituted C 3 -C 6 cycloalkenyl),

v. —NH(unsubstituted or substituted C 1 -C 6 haloalkyl),

w. —NH(unsubstituted or substituted C 1 -C 6 alkyl),

x. —N(unsubstituted or substituted C 2 -C 6 alkenyl) 2 ,

y. —N(unsubstituted or substituted C 2 -C 6 alkynyl) 2 ,

z. —N(unsubstituted or substituted C 3 -C 6 cycloalkyl) 2 ,

aa. —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl) 2 ,

bb. —N(unsubstituted or substituted C 1 -C 6 haloalkyl) 2 ,

cc. —N(unsubstituted or substituted C 1 -C 6 alkyl) 2 ,

dd. —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 alkyl),

ee. —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 2 -C 6 alkynyl),

ff. —N((unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl),

gg. —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl),

hh. —N(unsubstituted or substituted C 2 -C 6 alkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl),

ii. —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 alkyl),

jj. —N((unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkyl),

kk. —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl),

ll. —N(unsubstituted or substituted C 2 -C 6 alkynyl)(unsubstituted or substituted C 1 -C 6 haloalkyl),

mm. —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl),

nn. —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 3 -C 6 cycloalkenyl),

oo. —N(unsubstituted or substituted C 3 -C 6 cycloalkyl)(unsubstituted or substituted C 1 -C 6 haloalkyl),

pp. —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 alkyl),

qq. —N(unsubstituted or substituted C 3 -C 6 cycloalkenyl)(unsubstituted or substituted C 1 -C 6 haloalkyl),

rr. —N(unsubstituted or substituted C 1 -C 6 haloalkyl)(unsubstituted or substituted C 1 -C 6 alkyl),

ss. —C(═O)Z 4 ,

tt. —C(═O)OZ 4 ,

uu. —C(═O)NZ 10 Z 11 ,

vv. —NZ 5 C(═O)Z 4 ,

ww. —NZ 5 C(═O)OZ 4 ,

xx. —NZ 5 C(═O)NZ 10 Z 11 ,

yy. —S(═O) 2 Z 8 ,

zz. —S(═O) 2 NZ 10 Z 11 ,

aaa. —S(═O)(═NZ 6 )Z 4 ,

bbb. —S(═Z 6 )(═NZ 7 )Z 4 ,

ccc. —S(═O)(═NZ 6 )NZ 10 Z 11 ,

ddd. —NZ 5 S(═O) 2 Z 4 ,

eee. —NZ 5 S(═O) 2 NZ 10 Z 11 ,

fff. —NZ 5 S(═O)(═NZ 6 )Z 4 ,

ggg. —NZ 5 S(═NZ 6 )(═NZ 7 )Z 4 ,

hhh. —NZ 5 S(═O)(═NZ 6 )NZ 10 Z 11 ,

iii. C 1 -C 6 alkyl,

jjj. C 1 -C 6 haloalkyl,

kkk. C 3 -C 6 cycloalkyl, and

lll. 4- to 10-membered heterocycle,

(vi) unsubstituted or substituted C 3 -C 6 cycloalkenyl, 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 10 Z 11 and 4- to 8-membered heterocycle,

(vii) unsubstituted or substituted C 1 -C 6 haloalkyl, 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 10 Z 11 and 4- to 8-membered heterocycle, and

(viii) —NZ 8 Z 9 ; and

each of Z 10 and Z 11 is independently selected from the group consisting of:

(i) hydrogen,

(ii) unsubstituted or substituted C 1 -C 6 alkyl,

(iii) unsubstituted or substituted C 2 -C 6 alkenyl,

(iv) unsubstituted or substituted C 2 -C 6 alkynyl

(v) unsubstituted or substituted C 3 -C 6 cycloalkyl,

(vi) unsubstituted or substituted C 3 -C 6 cycloalkenyl, and

(vii) unsubstituted or substituted C 1 -C 6 haloalkyl.

2 . The compound of claim 1 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:

X 1 is selected from the group consisting of C and N;

X 2 is selected from the group consisting of C and N;

X 3 is selected from the group consisting of —CR 3 ═ and —CH═;

X 4 is selected from the group consisting of —CR 3 ═ and —CH═;

R i is selected from the group consisting of:

(i) —(CH 2 ) n —NZ 2 Z 3 ,

(ii) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH, and

(b) —C(═O)OH,

(iii) unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH, and

(b) —C(═O)OH,

(iv) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH,

(b) —C(═O)Z 1 , and

(v) unsubstituted or substituted 5- to 10-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH,

(b) —C(═O)OH, and

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

(a) —OH, and

(b) —C(═O)OH,

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

(a) —OH,

(b) —C(═O)OH, and

n is 0 or 1;

R 2 is selected from the group consisting of:

(i) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of:

(a) C 1 -C 6 alkyl,

(b) halogen, and

(ii) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:

(a) C 1 -C 6 alkyl,

(b) halogen, and

R 3 is selected from the group consisting of:

(a) hydrogen, and

(b) C 1 -C 6 haloalkyl;

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

(i) hydrogen,

(ii) C 1 -C 6 alkyl,

(iii) C 2 -C 6 alkenyl, and

(iv) —NZ 2 Z 3 ;

each Z 2 and Z 3 are 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:

(a) —OH, and

(b) —C(═O)OH,

(iii) —S(═O) 2 Z 4 ,

(iv) —(C═O)Z 4 ;

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

(i) C 1 -C 6 alkyl, and

(ii) C 2 -C 6 alkenyl.

3 . A compound of Formula II:

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

R 1 is selected from the group consisting of:

(i) —(CH 2 ) n —NZ 2 Z 3 ,

(ii) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH, and

(b) —C(═O)OH,

(iii) unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH, and

(b) —C(═O)OH,

(iv) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH,

(b) —C(═O)Z 1 , and

(v) unsubstituted or substituted 5- to 10-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH,

(b) —C(═O)OH, and

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

(a) —OH, and

(b) —C(═O)OH,

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

(a) —OH,

(b) —C(═O)OH, and

n is 0 or 1;

R 2 is selected from the group consisting of:

(i) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of:

(a) C 1 -C 6 alkyl,

(b) halogen, and

(ii) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:

(a) C 1 -C 6 alkyl,

(b) halogen, and

R 3 is selected from the group consisting of:

(i) hydrogen, and

(ii) C 1 -C 6 haloalkyl;

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

(i) hydrogen,

(ii) C 1 -C 6 alkyl,

(iii) C 2 -C 6 alkenyl, and

(iv) —NZ 2 Z 3 ;

each Z 2 and Z 3 are 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:

(d) —C(═O)OH,

(iii) —S(═O) 2 Z 4 ,

(iv) —(C═O)Z 4 ;

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

(i) C 1 -C 6 alkyl, and

(ii) C 2 -C 6 alkenyl.

4 . A compound of Formula III:

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

R 1 is selected from the group consisting of:

(i) —(CH 2 ) n NZ 2 Z 3 ,

(ii) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH, and

(b) —C(═O)OH,

(iii) unsubstituted or substituted 4- to 10-membered heterocycle, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH, and

(b) —C(═O)OH,

(iv) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH,

(b) —C(═O)Z 1 , and

(v) unsubstituted or substituted 5- to 10-membered heteroaryl, wherein one or more substituents are independently selected from the group consisting of:

(a) —OH,

(b) —C(═O)OH, and

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

(a) —OH, and

(b) —C(═O)OH,

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

(a) —OH,

(b) —C(═O)OH, and

n is 0 or 1;

R 2 is selected from the group consisting of:

(i) unsubstituted or substituted C 6 -C 10 aryl, wherein one or more substituents are independently selected from the group consisting of:

(a) C 1 -C 6 alkyl,

(b) halogen, and

(ii) unsubstituted or substituted C 3 -C 6 cycloalkyl, wherein one or more substituents are independently selected from the group consisting of:

(a) C 1 -C 6 alkyl,

(b) halogen, and

R 3 is selected from the group consisting of:

(i) hydrogen, and

(ii) C 1 -C 6 haloalkyl;

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

(i) hydrogen,

(ii) C 1 -C 6 alkyl,

(iii) C 2 -C 6 alkenyl, and

(iv) —NZ 2 Z 3 ;

each Z 2 and Z 3 are 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:

(e) —OH, and

(f) —C(═O)OH,

(iii) —S(═O) 2 Z 4 ,

(iv) —(C═O)Z 4 ;

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

(i) C 1 -C 6 alkyl, and

(ii) C 2 -C 6 alkenyl.

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

N((3-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-1-yl)methyl)acrylamide;

N((1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)methyl)acrylamide;

N((1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)methyl)propionamide;

N((1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl )methyl)methanesulfonamide;

N((3-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-1-yl)methyl)propionamide;

N((3-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-1-yl )methyl)methanesulfonamide;

(E)-3-(3-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-1-yl)acrylic acid;

(E)-3-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)acrylic acid;

N((6-(trifluoromethyl)-3-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-1-yl )methyl)acrylamide;

N((6-(trifluoromethyl)-3-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-1-yl )methyl)acetamide;

N((6-(trifluoromethyl)-3-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-1-yl )methyl)methanesulfonamide;

trans-2-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)cyclopropane-1-carboxylic acid;

2-hydroxy-4-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)benzaldehyde;

3-hydroxy-3-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)cyclobutane-1-carboxylic acid;

2-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)acetic acid;

1-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)azetidine-2-carboxylic acid;

1-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)azetidine-3-carboxylic acid;

cis-2-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)cyclopropane-1-carboxylic acid;

cis-3-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)cyclobutane-1-carboxylic acid;

trans-3-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)cyclobutane-1-carboxylic acid;

(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)glycine;

(E)-3-(6-(trifluoromethyl)-1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl )acrylic acid;

3-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)propanoic acid;

N-methyl-N—(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)glycine;

5-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)-1,3,4-oxadiazol-2(3H)-one;

N—((1-(4,4-difluorocyclohexyl)imidazo[1,5-a]pyridin-3-yl)methyl)acrylamide;

(E)—N-methyl-2-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)ethene-1-sulfonamide;

3-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)-1,2,4-oxadiazol-5(4H)-one;

5-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one; and

3-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)isoxazol-5(4H)-one.

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

(E)-3-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)acrylic acid; and

(E)—N-methyl-2-(1-(4-(trifluoromethyl)phenyl)imidazo[1,5-a]pyridin-3-yl)ethene-1-sulfonamide.

7 . A pharmaceutical composition comprising the compound of claim 1 , or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, and a pharmaceutically acceptable carrier.

8 - 12 . (canceled)

13 . A method for the prevention or treatment of a YAP/TAZ-TEAD activation mediated disorder in an animal, mammal or human comprising administering to said animal, mammal or human in need for such prevention or treatment an effective dose of the compound of claim 1 .

14 . The method of claim 13 , further comprising administering one or more additional medicines selected from the group consisting of EGFR inhibitors, MEK inhibitors, AXL inhibitors, B-RAF inhibitors, and RAS inhibitors.

Assignments (4)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 30, 2024

From: MARCHAND, ARNAUD; VANDERHOYDONCK, BART

To: CISTIM LEUVEN VZW

Reel/Frame 068745/0880 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 30, 2024

From: CISTIM LEUVEN VZW

To: KU LEUVEN R&D

Reel/Frame 068742/0960 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 30, 2024

From: KATHOLIEKE UNIVERSITEIT LEUVEN

To: KATHOLIEKE UNIVERSITEIT LEUVEN; VIB VZW

Reel/Frame 068743/0367 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2024

From: LAWHORN, BRIAN; GWALTNEY, STEPHEN L, II

To: SPRINGWORKS THERAPEUTICS, INC.

Reel/Frame 068059/0467 →