US 2025/0074881 A1Published application

Therapeutic compounds and methods of use

AssigneeGenentech, Inc.

InventorsJason 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

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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.

Claims35

Dependent claims

A compound of formula (I-AB):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:
L′ is
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 CR8, wherein R8 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, —CONRdR, —SO2Rd, —SO2NRd, —NRdSO2Re, and —NRdRe;
wherein each of Rd, Re and R 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 R8 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 Rf 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 R8 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;
whereinRd 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 C1-6alkynyl optionally substituted with —OH;
or Rx is cyclobutenyl, dihydrofuranyl, bicyclobutanyl, or cyclopentenyl;
or
Z is S(O)2Rx1, wherein Rx1 is C2-6alkenyl;
L is methylene, optionally substituted with one or more C1-6alkyl;
and
n and m are each 1;
or n and m are each 2.

24 more elements

A compound or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from any one of compounds of Table 1:

Structure
Compound Name
2-fluoro-1-[3-[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
1-[3-[4-[(lR)-1,2-dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro- prop-2-en-1-one
1-[3-[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-methyl- prop-2-en-1-one
2-fluoro-1-[3-[4-[l-(2- hydroxyethyl)pyrazol-4-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
2-fluoro-1-[3-[4-(1,2,4-triazol-4-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
1-[3-[4-[(1S)-1,2-dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro- prop-2-en-1-one
2-fluoro-1-[3-[4-[3-fluoro-3- (hydroxymethyl)azetidin-1-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop- 2-en-1-one
(E)-1-[3-[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-4- methoxy-but-2-en-1-one
1-[3-[4-(2,6-diazaspiro[3.3] heptan-2-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro- prop-2-en-1-one
N-[3-[1-(2-fluoroprop-2- enoyl)azetidin-3-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-4-yl]-2-hydroxy-acetamide
1-[3-[4-[1-[2- (dimethylamino)ethyl]pyrazol-4-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro- prop-2-en-1-one
1-[3-[4-ethynyl-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop- 2-en-1-one
(E)-4-hydroxy-1-[3-[4-(1H-pyrazol-4- yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]but-2-en- 1-one
3-fluoro-1-[3-[1-(2-fluoroprop-2- enoyl)azetidin-3-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-4-yl]azetidine-3-carboxamide
1-[3-[4-[3-[(1R)-1,2- dihydroxyethyl]azetidin-1-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro- prop-2-en-1-one
1-[3-[4-[(1S)-1,2-dihydroxyethyl]-1-[4- (pentafluoro-lambda6- sulfanyl)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro- prop-2-en-1-one
1-[3-[4-[(1R)-1,2-dihydroxyethyl]-1- [4-(pentafluoro-lambda6- sulfanyl)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro- prop-2-en-1-one
2-fluoro-1-[3-[4-imidazol-1-yl-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
(E,4R)-4-hydroxy-1-[3-[4- (hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]pent-2-en- 1-one
(E)-4-hydroxy-1-[3-[4-(3- hydroxyazetidin-1-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]but-2-en- 1-one
1-[3-[4-[(lR)-1,2-dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]but-2-yn- 1-one
cyclobuten-1-yl-[3-[4-[(1S)-1,2- dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]methanone
2-fluoro-1-[3-[4-[3-hydroxy-3- (hydroxymethyl)azetidin-1-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
2-fluoro-1-[3-[4-(3-hydroxyazetidin-1- yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[4,3- c]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
3-[1-[(E)-4-hydroxybut-2- enoyl]azetidin-3-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridine-4-carbonitrile
3-[1-(2-fluoroprop-2-enoyl)azetidin-3- yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridine-4-carbonitrile
2-fluoro-1-[3-[4-(3-hydroxyazetidin-1- yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
(3S)-1-[3-[l-(2-fluoroprop-2- enoyl)azetidin-3-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-4-yl]-3-hydroxy-pyrrolidin- 2-one
cyclobuten-1-yl-[3-[4- (hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]methanone
(E)-4-hydroxy-1-[3-[4- (hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]but-2-en- 1-one
(E)-1-[3-[4-[(1R)-1,2-dihydroxyethyl]- 1-4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-4- hydroxy-but-2-en-1-one
(E)-4-hydroxy-1-[3-[4-methyl-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]but-2-en- 1-one
(E,4S)-4-hydroxy-1-[3-[4- (hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]pent-2-en- 1-one
(E)-3-chloro-1-[3-[4-(hydroxymethyl)- 1-4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
(E)-4-hydroxy-1-[3-[4-(3- hydroxyazetidin-1-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[4,3- c]pyridin-3-yl]azetidin-1-yl]but-2-en-1- one
(E)-1-[3-[4-[(1S)-1,2-dihydroxyethyl]- 1-4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-4- hydroxy-but-2-en-1-one
2-chloro-1-[3-[4-[(1S)-1,2- dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
2-chloro-1-[3-[4-[(lR)-1,2- dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
1-[3-[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
1-[3-[4-[(lS)-1,2-dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
1-[3-[4-[(1R)-1,2-dihydroxyethyl]-1- [4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
cyclobuten-1-yl-[3-[4-[(1R)-1,2- dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]methanone
(E)-1-[3-[4-(hydroxymethyl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]but-2-en- 1-one
(E)-4-fluoro-N-[[4-(hydroxymethyl)-1- [4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]methyl]but-2-enamide
(3R)-1-[3-[l-(2-fluoroprop-2- enoyl)azetidin-3-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-4-yl]-3-hydroxy-pyrrolidin- 2-one
(E)-1-[3-[4-chloro-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-4- hydroxy-but-2-en-1-one
1-[3-[4-[(1S)-1,2-dihydroxyethyl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]but-2-yn- 1-one
2-fluoro-1-[3-[4-(1H-imidazol-4-yl)-1- [4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]prop-2-en- 1-one
1-[3-[4-(azetidin-3-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro- prop-2-en-1-one
(E)-4-fluoro-1-[3-[4-(3- hydroxyazetidin-1-yl)-1-[4- (trifluoromethoxy)phenyl]pyrazolo[4,3- c]pyridin-3-yl]azetidin-1-yl]but-2-en-1- one
1-[3-[4-[3-[(1S)-1,2- dihydroxyethyl]azetidin-1-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro- prop-2-en-1-one
1-[3-[4-[3,3- bis(hydroxymethyl)azetidin-1-yl]-1-[4- (trifluoromethoxy)phenyl]pyrazolo[3,4- b]pyridin-3-yl]azetidin-1-yl]-2-fluoro- prop-2-en-1-one
Cyclopent-1-en-1-yl(3-(4- (hydroxymethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)methanone
(E)-1-(3-(4-(Hydroxymethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)-2-methylbut-2-en-1-one
(2,5-Dihydrofuran-3-yl)(3-(4- (hydroxymethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)methanone
Bicyclo[1.1.0]butan-1-yl(3-(4- (hydroxymethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)methanone
(R)-Cyclobut-1-en-1-yl(3-(4-(1,2- dihydroxyethyl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)methanone
2-Fluoro-1-(3-(4-(1-methyl-1H- pyrazol-4-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- yl)prop-2-en-1-one
(S)-1-(3-(1-(Prop-1-en-2- ylsulfonyl)azetidin-3-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-4-yl)ethane-1,2- diol
(R)-1-(3-(1-(prop-1-en-2- ylsulfonyl)azetidin-3-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-4-yl)ethane-1,2- diol
(S,E)-1-(3-(1-(Prop-1-en-1- ylsulfonyl)azetidin-3-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-4-yl)ethane-1,2- diol
(R,E)-1-(3-(1-(prop-1-en-1- ylsulfonyl)azetidin-3-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-4-yl)ethane-1,2- diol
Cyclobut-1-en-1-yl(3-(1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyrazin-3-yl)azetidin-1- yl)methanone
N-(3-(4-(1-(difluoromethyl)-1H- pyrazol-4-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)-2-fluoroprop-2-en-1-one
2-fluoro-1-(3-(4-(1-(oxetan-3-yl)-1H- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)prop-2-en-1-one
2-fluoro-1-(3-(4-(1-(2-methoxyethyl)- 1H-pyrazol-4-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)prop-2-en-1-one
1-(3-(4-(1-cyclopropyl-!H-pyrazol-4- yl)-1-(4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)-2-fluoroprop-2-en-1-one
2-fluoro-1-(3-(4-(1-isopropyl-1H- pyrazol-4-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)prop-2-en-1-one
2-fluoro-1-(3-(4-(1-(2- (methylsulfonyl)ethyl)-1H-pyrazol-4- yl)-1-(4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)prop-2-en-1-one
2-(4-(3-(1-(2-fluoroacryloyl)azetidin-3- yl)-1-(4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-4-yl)-1H- pyrazol-1-yl)-N,N-dimethylacetamide
2-(4-(3-(1-(2-fluoroacryloyl)azetidin-3- yl)-1-(4-(trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-4-yl)-1H- pyrazol-1-yl)acetamide
1-(3-(4-(1H-pyrazol-4-yl)-1-(4- (trifluoromethoxy)phenyl)-1H- pyrazolo[3,4-b]pyridin-3-yl)azetidin-1- yl)-2-fluoroprop-2-en-1-one
1-(3-(1-(2-chloro-4- (trifluoromethoxy)phenyl)-4- (hydroxymethyl)-1H-pyrazolo[3,4- b]pyridin-3-yl)azetidin-1-yl)-2- fluoroprop-2-en-1-one
2-fluoro-1-(3-(4-(hydroxymethyl)-1-(2- methyl-4-(trifluoromethoxy)phenyl)- 1H-pyrazolo[3,4-b]pyridin-3- yl)azetidin-1-yl)prop-2-en-1-one
2-fluoro-1-(3-(1-(2-fluoro-4- (trifluoromethoxy)phenyl)-4- (hydroxymethyl)-1H-pyrazolo[3,4- b]pyridin-3-yl)azetidin-1-yl)prop-2-en- 1-one

74 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/823,182Filed 3 Sep 2024
Priority: 24 Nov 2021
Published: 6 Mar 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 231/56
Condensed with carbocyclic rings or ring systems: benzopyrazoles; Hydrogenated benzopyrazoles
A61P 35/00
Antineoplastic agents
C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
C07F 9/095
Esters of phosphoric acids: compounds containing the structure P-O-acyl, P-O-heteroatom, P-O-CN

Family

Application63/283,138Us provisional application · filed 24 Nov 2021
Application63/344,025Us provisional application · filed 19 May 2022
Application18/057,738Continuation · filed 21 Nov 2022
Application18/823,182Continuation
US 12,110,276 B2Related patent
US 2023/0202984 A1Published application
US 2025/0074881 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of formula (I-AB):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein:
L′ is
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 CR8, wherein R8 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, —CONRdR, —SO2Rd, —SO2NRd, —NRdSO2Re, and —NRdRe;
wherein each of Rd, Re and R 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 R8 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 Rf 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 R8 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;
whereinRd 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 C1-6alkynyl optionally substituted with —OH;
or Rx is cyclobutenyl, dihydrofuranyl, bicyclobutanyl, or cyclopentenyl;
or
Z is S(O)2Rx1, wherein Rx1 is C2-6alkenyl;
L is methylene, optionally substituted with one or more C1-6alkyl;
and
n and m are each 1;
or n and m are each 2.

24 more elements

Facts

Application

18/823,182Filed 3 Sep 2024

Priority

24 Nov 2021

Published

6 Mar 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 231/56
Condensed with carbocyclic rings or ring systems: benzopyrazoles; Hydrogenated benzopyrazoles
A61P 35/00
Antineoplastic agents
C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
C07F 9/095
Esters of phosphoric acids: compounds containing the structure P-O-acyl, P-O-heteroatom, P-O-CN

Family

Application63/283,138Us provisional application · filed 24 Nov 2021

Application63/344,025Us provisional application · filed 19 May 2022

Application18/057,738Continuation · filed 21 Nov 2022

Application18/823,182Continuation

US 12,110,276 B2Related patent

US 2023/0202984 A1Published application

US 2025/0074881 A1This patent

From the US filing history. Foreign family members aren’t listed.