# US 2022/0033409 A1 · Brm targeting compounds and associated methods of use

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- Number: US 2022/0033409 A1
- Document ID: US20220033409A1
- Status: Published application
- Kind: A1
- Application number: 17/343,341
- Filed: 2021-06-09
- Published: 2022-02-03
- Earliest claimed: 2020-06-09
- Assignees: Prelude Therapeutics Incorporated
- Applicants: Prelude Therapeutics, Incorporated
- Inventors: Hong Lin; Philip Pitis; Liang Lu; Andrew Paul Combs
- Web page: https://patentgrep.com/patent/US20220033409A1

## CPC

- A61P 35/00: Antineoplastic agents
- C07D 487/14: Ortho-condensed systems
- A61P 35/02: specific for leukemia
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present disclosure provides bifunctional compounds comprising a target protein binding moiety and a E3 ubiquitin ligase binding moiety, and associated methods of use.

## Claims

### Claim at position 1

-45. (canceled)

### Claim 46

A compound of Formula IA-7 or IA-8:
or a pharmaceutically acceptable salt or solvate thereof,
wherein:
R1 is a chemical moiety represented by the formula:
—(A)q—,
wherein:
q is an integer from 1 to 14;
each A is independently selected from the group consisting of CR1aR1b, O, S, SO, SO2, NR1c, SO2NR1c, SONR1c, SO(═NR1c), SO(═NR1c)NR1d, CONR1c, NR1cCONR1d, NR1cC(O)O, NR1cSO2NR1d, CO, CR1a═CR1b, C≡C, SiR1aR1b, P(O)R1a, P(O)OR1a, (CR1aR1b)1-4, —(CR1aR1b)1-4O(CR1aRth)1-4, —(CR1aR1b)1-4S(CR1aRth)1-4, —(CR1aR1b)1-4NR(CR1aR1b)1-4, NR1cC(═NCN)NR1dNR1cC(═NCN), NR1cC(═CNO2)NR1d, 3-11 membered cycloalkyl, optionally substituted with 0-6 R1a and/or R1b groups, 3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups, aryl optionally substituted with 0-6 R1a and/or R1b groups, or heteroaryl optionally substituted with 0-6 R1a and/or R1b groups,
wherein R1a, R1b, R1c, R1d and R1e are each independently, —H, D, -halo, —C1-C8alkyl, —O—C1-C8alkyl, —C1-C6haloalkyl, —N(C1-C8alkyl)2, 3-11 membered cycloalkyl, aryl, heteroaryl, 3-11 membered heterocyclyl, —O-(3-11 membered cycloalkyl), —S-(3-11 membered cycloalkyl), NH-(3-11 membered cycloalkyl), N(3-11 membered cycloalkyl)2, N-(3-11 membered cycloalkyl)(C1-C8alkyl), —OH, —NH2, —SH, —SO2C1-C8alkyl, SO(NH)C1-C8alkyl, P(O)(OC1-C8alkyl)(C1-C8alkyl), —P(O)(OC1-C8alkyl)2, —C≡C—C1-C8alkyl, —C≡CH, —CH═CH(C1-C8alkyl), —C(C1-C8alkyl)═CH(C1-C8alkyl), —C(C1-C8alkyl)═C(C1-C8alkyl)2, —Si(OH)3, —Si(C1-C8alkyl)3, —Si(OH)(C1-C8alkyl)2, —C(O)C1-C8alkyl, —CO2H, —CN, —CF3, —CHF2, —CH2F, —NO2, —SF5, —SO2NHC1-C8alkyl, —SO2N(C1-C8alkyl)2, —SO(NH)NHC1-C8alkyl, —SO(NH)N(C1-C8alkyl)2, —SONHC1-C8alkyl, —SON(C1-C8alkyl)2, —CONHC1-C8alkyl, —CON(C1-C8alkyl)2, —N(C1-C8alkyl)CONH(C1-C8alkyl), —N(C1-C8alkyl)CON(C1-C8alkyl)2, —NHCONH(C1-C8alkyl), —NHCON(C1-C8alkyl)2, —NHCONH2, —N(C1-C8alkyl)SO2NH(C1-C8alkyl), —N(C1-C8alkyl)SO2N(C1-C8alkyl)2, —NHSO2NH(C1-C8alkyl), —NHSO2N(C1-C8alkyl)2, or —NHSO2NH2; and where R1a or R1b, each independently may be optionally linked to other groups to form cycloalkyl and/or heterocyclyl moiety, optionally substituted with 0-4 R1e groups;
m=1 to 3;
W is optionally substituted —CH2—, —C(O)—, —S(O)—, or —S(O)2—; wherein when n=2 or 3, only one W may be —C(O)—, —S(O)—, or —S(O)2—;
Rc1 and Rd1 are independently H, D, Halo, C1-3 alkyl, C1-3 haloalkyl, or C1-4 alkoxyl;
Re3 is H, —C(O)Rf, or —P(O)(ORg)2; wherein Rf and Rg are independently H, C1-4 alkyl, C1-4 substituted alkyl, C3-8 cyclcoalkyl, C3-8 substituted cyclcoalkyl, C3-8 heterocyclcoalkyl, or C3-8 substituted heterocyclcoalkyl;
wherein;
X is optionally substituted —CH2—, or NH; or, if R1 is attached to X, then X is —CH— or N; and Q is optionally substituted —CH2—, optionally substituted —(CH2)2—, —C(O)—, optionally substituted —CH2C(O)—, —S(O)—, —S(O)2—, optionally substituted —CH2S(O)2—, or optionally substituted —CH2S(O)—
R9 is —CN or optionally substituted
V is H or F;
R4 is H, D, haloalkyl, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, —CORd, or —CONRe1Re2;
R7 is H, D, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted haloalkyl, Rd is H, or optionally substituted alkyl;
each Re1 and Re2 is independently H, D, optionally substituted alkyl,
or Re1 and Re2 together with the nitrogen atom to which they are attached form a 4-7 membered heterocyclyl.

### Claim 47

A compound, where said compound is a compound of Formula IA-9a or IA-10a:
or a pharmaceutically acceptable salt or solvate thereof,
wherein X is N or CH;
R1 is a chemical moiety represented by the formula:
—(A)q—,
wherein:
q is an integer from 1 to 14;
each A is independently selected from the group consisting of CR1aR1b, O, S, SO, SO2, NR1c, SO2NR1c, SONR1c, SO(═NR1c), SO(═NR1c)NR1d, CONR1c, NR1cCONR1d, NR1cC(O)O, NR1cSO2NR1d, CO, CR1a═CR1b, C≡C, SiR1aR1b, P(O)R1a, P(O)OR1a, (CR1aR1b)1-4, —(CR1aR1b)1-4O(CR1aR1b)1-4, —(CR1aR1b)1-4S(CR1aR1b)1-4, —(CR1aR1b)1-4NR(CR1aR1b)1-4 NR1cC(═NCN)NR1dNR1cC(═NCN), NR1cC(═CNO2)NR1d, 3-11 membered cycloalkyl, optionally substituted with 0-6 R1a and/or R1b groups, 3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups, aryl optionally substituted with 0-6 R1a and/or R1b groups, or heteroaryl optionally substituted with 0-6 R1a and/or R1b groups,
wherein R1a, R1b, R1c, R1d and R1e are each independently, —H, D, -halo, —C1-C8alkyl, —O—C1-C8alkyl, —C1-C6haloalkyl, —S—C1-C8alkyl, —NHC1-C8alkyl, —N(C1-C8alkyl)2, 3-11 membered cycloalkyl, aryl, heteroaryl, 3-11 membered heterocyclyl, —O-(3-11 membered cycloalkyl), —S-(3-11 membered cycloalkyl), NH-(3-11 membered cycloalkyl), N(3-11 membered cycloalkyl)2, N-(3-11 membered cycloalkyl)(C1-C8alkyl), —OH, —NH2, —SH, —SO2C1-C8alkyl, SO(NH)C1-C8alkyl, P(O)(OC1-C8alkyl)(C1-C8alkyl), —P(O)(OC1-C8alkyl)2, —C≡C—C2-C8alkyl, —C≡CH, —CH═CH(C1-C8alkyl), —C(C1-C8alkyl)═CH(C1-C8alkyl), —C(C1-C8alkyl)═C(C1-C8alkyl)2, —Si(OH)3, —Si(C1-C8alkyl)3, —Si(OH)(C1-C8alkyl)2, —C(O)C1-C8alkyl, —CO2H, —CN, —CF3, —CHF2, —NO2, —SF5, —SO2NHC1-C8alkyl, —SO2N(C1-C8alkyl)2, —SO(NH)NHC1-C8alkyl, —SO(NH)N(C1-C8alkyl)2, —SONHC1-C8alkyl, —SON(C1-C8alkyl)2, —CONHC1-C8alkyl, —CON(C1-C8alkyl)2, —N(C1-C8alkyl)CONH(C1-C8alkyl), —N(C1-C8alkyl)CON(C1-C8alkyl)2, —NHCONH(C1-C8alkyl), —NHCON(C1-C8alkyl)2, —NHCONH2, —N(C1-C8alkyl)SO2NH(C1-C8alkyl), —N(C1-C8alkyl)SO2N(C1-C8alkyl)2, —NHSO2NH(C1-C8alkyl), —NHSO2N(C1-C8alkyl)2, or —NHSO2NH2; and where R1a or R1b, each independently may be optionally linked to other groups to form cycloalkyl and/or heterocyclyl moiety, optionally substituted with 0-4 R1e groups;
n=0-3;
m=1 to 3;
Rk is C1-3 alkyl, and s=0 or 1
W is optionally substituted —CH2—, —C(O)—, —S(O)—, or —S(O)2—; wherein when n=2 or 3, only one W may be —C(O)—, —S(O)—, or —S(O)2—;
Rc1 and Rd1 are independently H, D, Halo, C1-3 alkyl, C1-3 haloalkyl, or C1-4 alkoxyl;
Re3 is H, —C(O)Rf, or —P(O)(ORg)2; wherein Rf and Rg are independently H, C1-4 alkyl, C1-4 substituted alkyl, C3-8 cyclcoalkyl, C3-8 substituted cyclcoalkyl, C3-8 heterocyclcoalkyl, or C3-8 substituted heterocyclcoalkyl;
wherein;
R9 is —CN or optionally substituted
V is H or F;
R4 is H, D, haloalkyl, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, —CORd, or —CONRe1Re2;
R7 is H, D, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted haloalkyl,
Rd is H, or optionally substituted alkyl;
each Re1 and Re2 is independently H, D, optionally substituted alkyl,
or Re1 and Re2 together with the nitrogen atom to which they are attached form a 4-7 membered heterocycyl.

### Claim 48 (depends on 47)

The compound according to claim 47, wherein the compound is a compound of formula IA-11 or IA-12:
wherein W is —CH2— or —CH(CH3)—;
X is N or CH;
each Rk is independently C1-3 alkyl, and s=0 or 1;
R1 is:
a covalent bond;
-3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups;
3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups;
—(CR1aR1b)1-5;
—(CR1a═CR1b)—;
—(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—A—(CR1aR1b)1-5— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—A—(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—(CR1a═R1b)—(CR1aR1b)1-5—;
—(CR1aR1b)1-5—(CR1a═CR1b)—(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—(C≡C)—(CR1aR1b)1-5—;
—(CR1aR1b)1-5—(C≡C)—(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
—(C≡C)—(CR1aR1b)1-5—A—(CR1aR1b)1-5— wherein A is O, S, or NR1c;
—(C≡C)—(CR1aR1b)1-5;
—(CR1aR1b)1-5-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-;
—(CR1aR1b)1-5-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-;
(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—;
(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups) —(CR1aR1b)1-5—;
—(CR1aR1b)1-5-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5;
—(CR1aR1b)1-5-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—A-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)- wherein A is O, S, or NR1c;
—(CR1aR1b)1-5-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5;
—(CR1aR1b)1-5-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—A-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)- wherein A is O, S, or NR1c;
—(CR1aR1b)1-5-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—A-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)- wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—A-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein each A is independently O, S, or NR1c;
—(CR1aR1b)1-5—A-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein each A is independently O, S, or NR1c;
—(CR1aR1b)1-5—A—(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—A—(CR1aR1b)1-5—A—(CR1aR1b)1-5—A—(CR1aR1b)1-5-A— wherein each A is independently O, S, or NR1c;
—(CR1aR1b)1-5—A—(CO) wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—(CR1a═R1b)—(CR1aR1b)1-5—A—(CO)— wherein A is O, S, or NR1c;
(CR1aR1b)1-5—(C≡C)—(CR1aR1b)1-5—A—(CO)— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A—(CO)— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—A—(CO)-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)- wherein A is O, S, or NR1c;
—(CR1aR1b)1-5-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A—(CO)— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—A—(CO)-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)- wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—A-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-A—(CO)— wherein each A is independently O, S, or NR1c;
(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-CO—(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A-(CO)— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A-(CO)— wherein A is O, S, or NR1c;
(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—;
(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—;
A-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein each A is independently O, S, or NR1c;
(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-A—(CR1aR1b)1-5—A— wherein each A is independently O, S, or NR1c;
(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CO)—A—(CR1aR1b)1-5— wherein A is O, S, or NR1c;
(heteroaryl optionally substituted with 0-4 R1a and/or R1b groups)-A—(CR1aR1b)1-5—wherein A is O, S, or NR1c;
(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CO)—(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CO)—A—(CR1aR1b)1-5— wherein A is O, S, or NR1c; or
—(CO)-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
R4 is H, —CH3, or —CH2OH;
R7 is —C(CH3)3 or —CH(CH3)2; and
R9 is —CN, optionally substituted heteroaryl,
R1a, R1b, R1c, and R1e are each independently, —H, D, -halo, —C1-C8alkyl, —C1-C6haloalkyl, —O—C1-C8alkyl, —S—C1-C8alkyl, —N(C1-C8alkyl)2, 3-11 membered cycloalkyl, aryl, heteroaryl, 3-11 membered heterocyclyl, —O-(3-11 membered cycloalkyl), —S-(3-11 membered cycloalkyl), NH-(3-11 membered cycloalkyl), N(3-11 membered cycloalkyl)2, N-(3-11 membered cycloalkyl)(C1-C8alkyl), —OH, —NH2, —SH, —SO2C1-C8alkyl, SO(NH)C1-C8alkyl, P(O)(OC1-C8alkyl)(C1-C8alkyl), —P(O)(OC1-C8alkyl)2, —CH═CH(C1-C8alkyl), —C(C1-C8alkyl)═CH(C1-C8alkyl), —C(C1-C8alkyl)═C(C1-C8alkyl)2, —Si(OH)3, —Si(C1-C8alkyl)3, —Si(OH)(C1-C8alkyl)2, —C(O)C1-C8alkyl, —CO2H, —CN, —CF3, —CHF2, —CH2F, —NO2, —SF5, —SO2NHC1-C8alkyl, —SO2N(C1-C8alkyl)2, —SO(NH)NHC1-C8alkyl, —SO(NH)N(C1-C8alkyl)2, —SONHC1-C8alkyl, —SON(C1-C8alkyl)2, —CONHC1-C8alkyl, —CON(C1-C8alkyl)2, —N(C1-C8alkyl)CONH(C1-C8alkyl), —N(C1-C8alkyl)CON(C1-C8alkyl)2, —NHCONH(C1-C8alkyl), —NHCON(C1-C8alkyl)2, —NHCONH2, —N(C1-C8alkyl)SO2NH(C1-C8alkyl), —N(C1-C8alkyl)SO2N(C1-C8alkyl)2, —NHSO2NH(C1-C8alkyl), —NHSO2N(C1-C8alkyl)2, or —NHSO2NH2, or where R1a or R1b, each independently may be optionally linked to other groups to form cycloalkyl and/or heterocyclyl moiety, optionally substituted with 0-4 R1e groups.

### Claim 49 (depends on 48)

The compound according to claim 48, wherein W is —CH2—.

### Claim 50 (depends on 48)

The compound according to claim 48, wherein R4 is —CH3.

### Claim 51 (depends on 48)

The compound according to claim 48,
wherein R9 is

### Claim 52 (depends on 48)

The compound according to claim 48, wherein R1 is:
—(CR1aR1b)1-5;
—(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5—A—(CR1aR1b)1-5— wherein A is O, S, or NR1c;
-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CO)—(CR1aR1b)1-5—A- wherein A is O, S, or NR1c;
-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CO)—A—(CR1aR1b)1-5— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-A— wherein A is O, S, or NR1c;
—(CR1aR1b)1-5-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5;
—(CR1aR1b)1-5-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c; —A-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein each A is independently O, S, or NR1c;
-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-A—(CR1aR1b)1-5—A— wherein each A is independently O, S, or NR1c;
-(3-11 membered heterocyclyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
-(heteroaryl optionally substituted with 0-4 R1a and/or R1b groups)-A—(CR1aR1b)1-5— wherein A is O, S, or NR1c;
-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CO)—(CR1aR1b)1-5—A— wherein A is O, S, or NR1c;
-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CO)—A—(CR1aR1b)1-5— wherein A is O, S, or NR1c; or
—(CO)-(3-11 membered cycloalkyl optionally substituted with 0-6 R1a and/or R1b groups)-(CR1aR1b)1-5—A— wherein A is O, S, or NR1c.

### Claim 53 (depends on 48)

The compound according to claim 48, wherein each R1a, each R1b, and each R1c is independently H or C1-C6alkyl.

### Claim 54 (depends on 48)

The compound according to claim 48, wherein the compound of Formula I is a compound of formula IA-13a, IA-13b, IA-14a or IA-14b:
wherein X is N or CH.

### Claim 55 (depends on 54)

The compound according to claim 54, wherein R1 is -(3-11 membered heterocyclyl)-(CR1aR1b)1-3—O—, wherein each R1a is H and each R1b is independently H, C1-C8alkyl, or preferably CH3.

### Claim 56 (depends on 54)

The compound according to claim 54, wherein R1 is -(3-11 membered heterocyclyl)-(CO)—(CR1aR1b)1-3—O— wherein each R1a is H and each R1b is independently H, C1-C8alkyl, or CH3.

### Claim 57 (depends on 54)

The compound according to claim 54, wherein the compound is a compound of formula IA-15a, IA-15b, IA-16a, or IA-16b:
wherein A is O, S, or NR1c,
R1a1 is H or —C1-C8alkyl, —CH2CH3, or —CH3;
R1c is —H, or —C1-C8alkyl, CH3;
A1 is a covalent bond or —(CR1aR1b)1-3.

### Claim 58 (depends on 57)

The compound according to claim 57, wherein A is O and R1a1 is —C1-C8alkyl, —CH2CH3, or —CH3.

### Claim 59 (depends on 57)

The compound according to claim 57, wherein A1 is a covalent bond.

### Claim at position 16

-87. (canceled)

### Claim 88 (depends on 57)

The compound according to claim 57, wherein A is O.

### Claim 89

(canceled)

### Claim 90 (depends on 47)

A pharmaceutical composition comprising a compound according to claim 47 and a pharmaceutically acceptable excipient.

### Claim 91 (depends on 47)

A method of treating cancer in a subject in need thereof comprising administering to the subject a compound of claim 47.

### Claim 92 (depends on 91)

The method of claim 91, wherein the cancer harbors a SMARCA4 mutation.

### Claim 93 (depends on 91)

The method of either one of claim 91, wherein the cancer is squamous-cell carcinoma, basal cell carcinoma, adenocarcinoma, hepatocellular carcinomas, and renal cell carcinomas, cancer of the bladder, bowel, breast, cervix, colon, esophagus, head, kidney, liver, lung, neck, ovary, pancreas, prostate, and stomach; leukemias; benign and malignant lymphomas, particularly Burkitt's lymphoma and Non-Hodgkin's lymphoma; benign and malignant melanomas; myeloproliferative diseases; sarcomas, including Ewing's sarcoma, hemangiosarcoma, Kaposi's sarcoma, liposarcoma, myosarcomas, peripheral neuroepithelioma, synovial sarcoma, gliomas, astrocytomas, oligodendrogliomas, ependymomas, gliobastomas, neuroblastomas, ganglioneuromas, gangliogliomas, medulloblastomas, pineal cell tumors, meningiomas, meningeal sarcomas, neurofibromas, and Schwannomas; bowel cancer, breast cancer, prostate cancer, cervical cancer, uterine cancer, lung cancer, ovarian cancer, testicular cancer, thyroid cancer, astrocytoma, esophageal cancer, pancreatic cancer, stomach cancer, liver cancer, colon cancer, melanoma; carcinosarcoma, Hodgkin's disease, Wilms' tumor and teratocarcinomas, T-lineage Acute lymphoblastic Leukemia (T-ALL), T-lineage lymphoblastic Lymphoma (T-LL), Peripheral T-cell lymphoma, Adult T-cell Leukemia, Pre-B ALL, Pre-B Lymphomas, Large B-cell Lymphoma, Burkitts Lymphoma, B-cell ALL, Philadelphia chromosome positive ALL and Philadelphia chromosome positive CIVIL.