# US 12,110,276 B2 · Pyrazolo compounds and methods of use thereof

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- Number: US 12,110,276 B2
- Document ID: US12110276B2
- Status: Granted
- Kind: B2
- Application number: 18/057,738
- Filed: 2022-11-21
- Published: 2023-06-29
- Granted: 2024-10-08
- Earliest claimed: 2021-11-24
- Assignees: Genentech, Inc.
- Applicants: Genentech, Inc.
- Inventors: Jason Robert Zbieg; Russell Tyler Smith; Paul Powell Beroza; Vishal Anil Verma; Bing-Yan Zhu; Ramsay Beveridge; Lisa Marie Barton; Bryan Ka Ip Chan; Curtis Colwell; Samir Bouayad-Gervais; Anwesha Dey; Marie Anne Evangelista
- Web page: https://patentgrep.com/patent/US12110276B2

## CPC

- C07D 231/56: Benzopyrazoles; Hydrogenated benzopyrazoles
- A61P 35/00: Antineoplastic agents
- C07D 471/04: Ortho-condensed systems
- C07F 9/095: {Compounds containing the structure P(=O)-O-acyl, P(=O)-O-heteroatom, P(=O)-O-CN}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

This disclosure relates to compounds and methods of using said compounds, as well as pharmaceutical compositions containing such compounds, for treating diseases and conditions mediated by TEAD, such as cancer.

## Claims

### Claim 1

A compound of formula (I-AB):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:
L′ is *—N(R1)-L-**, wherein * denotes the point of attachment to Z, and ** denotes the point of attachment to
R1 is H or C1-6 alkyl;
X1 is N or CRs, wherein Rs is selected from H, deuterium, —CN, halo, C1-15alkyl, C1-6alkynyl, C6-20aryl, 5 to 15 membered heteroaryl, C3-20cycloalkyl, 3 to 15 membered heterocyclyl, —OH, —ORf, C1-15alkoxy, —NRdCORe, —CONRdRe, —SO2Rd, —SO2NRdRe, —NRdSO2Re, and —NRdRe;
wherein each of Rd, Re and Rf are independently H, C1-6alkyl, or C3-20cycloalkyl, wherein each of C1-6alkyl and C3-20cycloalkyl are independently optionally substituted with one or more halo, oxo, —OH, or —CN;
wherein the C1-15alkyl and C1-15alkoxy of Rs are each independently optionally substituted with one or more Rt1, wherein Rt1 is independently, at each occurrence, selected from halo, oxo, —OH, —OR1, —CN, —NRdRe, and 3 to 15 membered heterocyclyl optionally substituted with one or more —OH; wherein Rf1 is —C(O)CH2NRdRe, —C(O)C1-6alkyl, —P(O)(OH)2; wherein Rd and Re are each independently H or C1-6alkyl, and the C1-6alkyl of Rd or Re is optionally substituted with one or more halo, oxo, —OH, or —CN; and
wherein the C6-20aryl, 5 to 15 membered heteroaryl, C3-20cycloalkyl, and 3 to 15 membered heterocyclyl of Rs are each independently optionally substituted with one or more Rt2, wherein Rt2 is independently, at each occurrence, selected from halo, oxo, —OH, —CN, C(O)NH2, —C(O)NRdRe, —NRdRe, C1-6alkoxyl, 3 to 6 membered heterocyclyl, C3-6cycloalkyl, and C1-6alkyl; wherein the C1-6alkyl of Rt2 is optionally substituted with one or more —OH, C1-6alkoxyl, halo, oxo, —S(O)2CH3, or —NRdRe; wherein Rd and Re are each independently H, —C(O)CH3, —C(O)C1-6alkyl, or C1-6alkyl;
X2, X3, and X4 are each independently N, CH, or CD, provided that: 1) only one of X1, X2, X3, and X4 is N; or 2) X1 is N, X2 is CH, X3 is CH, and X4 is N; or 3) X1 is CRs and X2, X3, and X4 are each independently CH or CD;
B is phenyl or 5 to 6 membered heteroaryl, wherein the phenyl or 5 to 6 membered heteroaryl of B are each independently optionally substituted with one or more R, wherein R is independently at each occurrence selected from halo, C1-15alkyl, C1-6alkoxy, and S(Ry)5, wherein each Ry is halo, and wherein the C1-15alkyl or C1-6alkoxy of Rt is optionally substituted with one or more halo;
Z is —C(O)Rx, wherein Rx is C2-6alkenyl, optionally substituted with one or more substituents selected from C1-6alkyl, deuterium, —OH, C1-6alkoxyl, and halo; or Rx is C1-6alkyl, optionally substituted with one or more halo; or Rx is C1-6alkynyl optionally substituted with —OH; or Rx is cyclobutenyl, dihydrofuranyl, bicyclobutanyl, or cyclopentenyl; or
Z is S(O)2Rx1, wherein Rx1 is C2-6alkenyl; and
L is methylene, optionally substituted with one or more C1-6alkyl.

### Claim 2 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-A):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein Ra, Rb, and Rc are each independently H, deuterium, —OH, C1-6alkoxyl, halo, or C1-5alkyl.

### Claim 3 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (A-1):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-A-1):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:
Ra, Rb, and Rc are each independently H, halo, deuterium, —OH, C1-6alkoxyl, or C1-5alkyl; and
Rt is selected from halo, C1-15alkyl, C1-6alkoxy, and S(Ry)5, wherein each Ry is halo, and wherein the C1-15alkyl or C1-6alkoxy of Rt is optionally substituted with one or more halo.

### Claim 5 (depends on 2)

The compound of claim 2, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-A-5):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 5)

The compound of claim 5, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-A-12):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 6)

The compound of claim 6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (I-A-13):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the R of B is —SF5, —O—CHF2, or —O—CF3.

### Claim 9 (depends on 1)

The compound of claim 1 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein Z is —C(O)Rx and Rx is C2-6alkenyl optionally substituted with one or more substituents selected from C1-6alkyl, deuterium, —OH, C1-6alkoxyl, and halo; or Rx is C1-6alkyl optionally substituted with one or more halo.

### Claim 10 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof or a pharmaceutically acceptable salt thereof, wherein X1 is CRs; and X2, X3, and X4 are CH.

### Claim 11 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof or a pharmaceutically acceptable salt thereof, wherein X1 is CRs; X2 and X3 are CH; and X4 is N.

### Claim 12 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein Rs is H, halo, or —CN.

### Claim 13 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein Rs is —ORf, wherein Rf is C3-20cycloalkyl optionally substituted with one or more —OH.

### Claim 14 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein Rs is C1-15alkyl or C1-15alkoxy, wherein the C1-15alkyl or C1-15alkoxy of Rs are each independently optionally substituted with one or more Rt1, wherein Rt1 is independently, at each occurrence, selected from halo, oxo, —OH, —ORf1, —CN, —NRdRe, and 3 to 15 membered heterocyclyl optionally substituted with one or more —OH; wherein Rf1 is —C(O)CH2NRdRe, —C(O)C1-6alkyl, —P(O)(OH)2; wherein Rd and Re are each independently H or C1-6alkyl, and the C1-6alkyl of Rd or Re is optionally substituted with one or more halo, oxo, —OH, or —CN.

### Claim 15 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein Rs is —NRdRe, wherein Rd and Re are each independently selected from the group consisting of H, C1-6alkyl, C3-20cycloalkyl, —C(O)Rt, wherein Rt is C1-6alkyl, wherein each of C1-6alkyl, C3-20cycloalkyl are optionally substituted with one or more —OH.

### Claim 16 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein Rs is —C(O)NRdRe, wherein Rd and Re are each independently selected from the group consisting of H and C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more —OH.

### Claim 17 (depends on 1)

The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein Rs is C1-6alkyl optionally substituted with one or more —OH.

### Claim 18 (depends on 1)

The compound of claim 1 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein Rs is selected from the group consisting of

### Claim 19 (depends on 1)

The compound of claim 1 or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:
Compound
Number
Structure
Compound Name
1
N-((1-(4-(trifluoromethoxy)phenyl)- 1H-indazol-3-yl)methyl)acrylamide
2
2-chloro-N-((1-(4- (trifluoromethoxy)phenyl)-1H-indazol- 3-yl)methyl)acetamide
3
N-((l-(4-(pentafluoro-λ6- sulfaneyl)phenyl)-1H-indazol-3- yl)methyl)acrylamide
4
N-((4-(hydroxymethyl)-1-(4- (trifluoromethoxy)phenyl)-1H-indazol- 3-yl)methyl)acrylamide
5
N-((4-(hydroxymethyl)-1-(4- (pentafluoro-λ6-sulfaneyl)phenyl)-1H- indazol-3-yl)methyl)acrylamide
6
N-((4-(1,2-dihydroxyethyl)-1-(4- (trifluoromethoxy)phenyl)-1H-indazol- 3-yl)methyl)acrylamide
7
(R)-N-((4-(1,2-dihydroxyethyl)-1-(4- (trifluoromethoxy)phenyl)-1H-indazol- 3-yl)methyl)acrylamide
8
(S)-N-((4-(1,2-dihydroxyethyl)-1-(4- (trifluoromethoxy)phenyl)-1H-indazol- 3-yl)methyl)acrylamide
9
N-((4-(1,2-dihydroxyethyl)-1-(4- (pentafluoro-λ6-sulfaneyl)phenyl)-1H- indazol-3-yl)methyl)acrylamide
10
(R)-N-((4-(1,2-dihydroxyethyl)-1-(4- (pentafluoro-λ6-sulfaneyl)phenyl)-1H- indazol-3-yl)methyl)acrylamide
11
(S)-N-((4-(1,2-dihydroxyethyl)-1-(4- (pentafluoro-λ6-sulfaneyl)phenyl)-1H- indazol-3-yl)methyl)acrylamide
12
N-((l-(4-(pentafluoro-λ6- sulfaneyl)phenyl)-1H-pyrazolo[4,3- b]pyridin-3-yl)methyl)acrylamide
13
N-((l-(4-(pentafluoro-λ6- sulfaneyl)phenyl)-1H-pyrazolo[3,4- b]pyridin-3-yl)methyl)acrylamide
14
N-((4-cyano-1-(4-(pentafluoro-λ6- sulfaneyl)phenyl)-1H-indazol-3- yl)methyl)acrylamide
15
N-[[4-(1,2-dihydroxyethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl]methyl]acrylamide
16
(R)-N-[[4-(1,2-dihydroxyethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl]methyl]acrylamide
17
(S)-N-[[4-(1,2-dihydroxyethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl]methyl]acrylamide
18
N-methyl-N-((1-(4- (trifluoromethoxy)phenyl)-1H-indazol- 3-yl)methyl)acrylamide
19
2-chloro-N-methyl-N-((1-(4- (trifluoromethoxy)phenyl)-1H-indazol- 3-yl)methyl)acetamide
23
N-[[1-[4-(pentafluoro-lambda6- sulfanyl)phenyl]-4-[rac-(1S)-1,2- dihydroxyethyl]pyrazolo[3,4-b]pyridin- 3-yl]methyl]prop-2-enamide
24
N-[[4-[(2-hydroxyacetyl)amino]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
25
N-(2-hydroxyethyl)-3-[(prop-2- enoylamino)methyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridine-4-carboxamide
26
(Z)-3-chloro-N-[[4-[(1R)-1,2- dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
27
N-[[1-[4-(pentafluoro-lambda6- sulfanyl)phenyl]-4-[rac-(1R)-1,2- dihydroxyethyl]pyrazolo[3,4-b]pyridin- 3-yl]methyl]prop-2-enamide
30
N-methyl-3-[(prop-2- enoylamino)methyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridine-4-carboxamide
32
N-[[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
33
N-[[4-[(3S)-3-hydroxy-1-piperidyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
34
N-[[4-(3-hydroxycyclobutoxy)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
35
N-[[4-[l-(2-hydroxyethyl)pyrazol-4-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
36
N-[[4-(2-hydroxyethylamino)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
37
(E)-3-chloro-N-[[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
38
N-[[4-(3-hydroxycyclobutyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
43
N-[[4-[3-(hydroxymethyl)azetidin- 1-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
44
N-[[4-(1H-1,2,4-triazol-3-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
46
N-[[4-[(3S)-3-hydroxypyrrolidin-1-yl]-1-4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
47
N-[[4-[(3R)-3-hydroxypyrrolidin-1-yl]-1-4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
49
2-chloro-N-[[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
51
N-[[4-(1H-triazol-4-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
52
N-[[4-(3-cyanoazetidin-1-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
53
(Z)-3-chloro-N-[[4-[(1S)-1,2- dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
54
N-[[4-[(3-hydroxyazetidin-1- yl)methyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
55
N-[[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]-N-methyl-prop- 2-enamide
56
N-[[4-(3-hydroxycyclobutyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
61
(E)-N-[[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]but-2-enamide
62
N-[[4-[(lR)-1-hydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
63
N-[[4-[(1S)-1-hydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
65
N-[[4-[(3R)-3-hydroxy-1-piperidyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
67
N-[[4-(3-hydroxycyclobutoxy)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
68
2-fluoro-N-[[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
69
(E)-4,4-difluoro-N-[[4- (hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]but-2-enamide
73
N-[[4-[rac-(1S)-1,2-dihydroxyethyl]-1-[3- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
74
N-[[4-(3-hydroxy-3-methyl-azetidin-1- yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
76
N-[[4-(6-hydroxy-2- azaspiro[3.3]heptan-2-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
77
N-[[4-morpholino-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
83
N-[[4-(1H-pyrazol-3-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
84
N-[[4-(3-fluoroazetidin-1-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
85
N-[[4-[(3-hydroxycyclobutyl)amino]-1- [4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
86
N-[[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-ynamide
87
N-[[4-(hydroxymethyl)-1-[4- (pentafluoro-lambda6- sulfanyl)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
88
N-[[4-[rac-(lR)-1,2-dihydroxyethyl]-1- [4- (trifluoromethyl)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
90
N-[[4-[(3-hydroxycyclobutyl)-methyl- amino]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
91
N-[[4-(4-hydroxy-1-piperidyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
92
N-[[4-(3-aminoazetidin-1-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
93
N-[[4-[(1R)-1,2-dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]-N-methyl-prop- 2-enamide
98
N-[[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]but-2-ynamide
99
(Z)-3-chloro-N-[[4-(hydroxymethyl)-1- [4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
100
N-[[4-[rac-(1S)-1,2-dihydroxyethyl]-1- [4- (trifluoromethyl)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
101
N-[[4-[2-hydroxyethyl(methyl)amino]- 1-4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
104
3-[(prop-2-enoylamino)methyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridine-4-carboxamide
105
N-[[4-[(dimethylamino)methyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
106
N-[[4-(3-hydroxyazetidin-1-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
107
N-[[4-[3-(dimethylamino)azetidin-1- yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
111
2,3,3-trideuterio-N-[[4- (hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
116
N-[[4-(3-acetamidoazetidin-1-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
117
N-[[4-[(3-hydroxycyclobutyl)-methyl- amino]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
118
N-[[4-(3-methoxyazetidin-1-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
119
N-[[4-(IH-imidazol-4-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
121
(E)-4-fluoro-N-[[4-(hydroxymethyl)-1- [4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]but-2-enamide
122
N-[[4-[3-(methylamino)azetidin-1-yl]- 1-4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
123
N-[[4-[3-[(1R)-1- hydroxyethyl]azetidin-1-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
124
N-[[4-[3-hydroxy-3- (hydroxymethyl)azetidin-1-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
126
N-[[4-(2-hydroxyethoxy)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
128
4-hydroxy-N-[[4-(hydroxymethyl)-1- [4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]but-2-ynamide
131
N-[[4-[rac-(lR)-1,2-dihydroxyethyl]-1- 3- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
132
(E)-4,4,4-trifluoro-N-[[4- (hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]but-2-enamide
134
N-[[4-(1H-pyrazol-4-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
135
N-[[4-(1-hydroxy-1-methyl-ethyl)-1- [4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
136
N-[[4-[3-(1-hydroxy-1-methyl- ethyl)azetidin-1-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
138
N-[[4-[3-[(1S)-1- hydroxyethyl]azetidin-1-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
139
N-[[4-[(1S)-1,2-dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]-N-methyl-prop- 2-enamide
140
N-[[l-[4-(difluoromethoxy)phenyl]-4- (hydroxymethyl)pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
143
N-[[4-[(3-hydroxycyclobutyl)amino]-1- [4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]prop-2-enamide
144
(S)-N-((4-(2-Oxo-1,3-dioxolan-4-yl)-1- (4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
145
(S)-2-(3-(Acrylamidomethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-4-yl)-2- hydroxyethyl2-aminoacetateformate
146
(S)-2-(3-(Acrylamidomethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-4-yl)-2- hydroxyethylacetate
147
(S)-2-(3-(Acrylamidomethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-4-yl)-2- hydroxyethyldihydrogenphosphate
148
N-((4-(Hydroxymethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)cyclobut-1-enecarboxamide
149
N-((4-(Hydroxymethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)methyl)- 2,5-dihydrofuran-3-carboxamide
154
(S)-N-((4-(1,2-Dihydroxyethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide-2,3,3-d3
155
(S)-N-((4-(1,2-Dihydroxyethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)methyl)-2- fluoroacrylamide
156
(S)-N-((4-(1,2-Dihydroxyethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)cyclobut-1-enecarboxamide
164
N-((4-(l-Methyl-IH-pyrazol-4-yl)-1- (4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
165
N-((4-(1-(2-amino-2-oxoethyl)-1H- pyrazol-4-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
166
N-((4-(1-(2-(dimethylamino)-2- oxoethyl)-1H-pyrazol-4-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
167
N-((4-(1-(2-methoxyethyl)-1H-pyrazol- 4-yl)-1-(4-(trifluoromethoxy)phenyl)- 1H-pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
168
N-((4-(1-(methylsulfonyl)ethyl)-1H-pyrazol- pyrazol-4-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
169
N-((4-(1-(difluoromethyl)-1H-pyrazol- 4-yl)-1-(4-(trifluoromethoxy)phenyl)- 1H-pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
170
N-((4-(1-isopropyl-1H-pyrazol-4-yl)-1- (4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
171
N-((4-(1-(oxetan-3-yl)-1H-pyrazol-4- yl)-1-(4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
172
pyrazol-4-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
173
N-((4-(1-cycloprpyl-1H-pyrazol-4- yl)-1-(4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
186
N-((4-cyano-1-(4- (trifluoromethoxy)phenyl)-1H-indazol- 3-yl)methyl)acrylamide
187
N-((1-(4-(trifluoromethoxy)phenyl)- 1H-pyrazolo[4,3-b]pyridin-3- yl)methyl)acrylamide
188
N-((1-(4-(trifluoromethoxy)phenyl)- 1H-pyrazolo[3,4-b]pyridin-3- yl)methyl)acrylamide
or a pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 1)

A pharmaceutical composition, comprising (i) a compound of claim 1, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and (ii) a pharmaceutically acceptable carrier, diluent, or excipient.

### Claim 21 (depends on 1)

A method for treating cancer in a mammal, comprising administering a therapeutically effective amount of a compound of claim 1, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, to the mammal.

### Claim 22 (depends on 1)

A method for treating a disease or condition mediated by TEAD activity in a mammal, comprising administering a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, to the mammal, wherein the disease or condition is selected from the group consisting of acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphagioendotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin's and non-Hodgkin's), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, thyroid cancer, Waldenstrom's macroglobulinemia, testicular tumors, uterine cancer and Wilms' tumor.

### Claim 23 (depends on 1)

A composition, comprising: (i) one or more TEAD inhibitors, or a pharmaceutically acceptable salt thereof; and (ii) one or more KRAS inhibitors, or a pharmaceutically acceptable salt thereof,
wherein the one or more TEAD inhibitors comprise a compound of claim 1.

### Claim 24 (depends on 1)

A method of treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of a combination, comprising: i) one or more TEAD inhibitors, or a pharmaceutically acceptable salt thereof; and (ii) one or more KRAS inhibitors, or a pharmaceutically acceptable salt thereof,
wherein the one or more TEAD inhibitors comprise a compound of claim 1.

### Claim 25 (depends on 1)

A method of reducing resistance of a subject to treatment comprising a KRAS inhibitor, wherein the method comprises administering a therapeutically effective amount of a TEAD inhibitor, or a pharmaceutically acceptable salt thereof, wherein the TEAD inhibitor is a compound of claim 1.

### Claim 26 (depends on 19)

The compound of claim 19, wherein the compound is:
or a pharmaceutically acceptable salt thereof.

### Claim 27 (depends on 19)

The compound of claim 19, wherein the compound is:
or a pharmaceutically acceptable salt thereof.

### Claim 28 (depends on 19)

The compound of claim 19, wherein the compound is:
or a pharmaceutically acceptable salt thereof.