US 11,702,423 B2
BRM targeting compounds and associated methods of use
Hong Lin, Exton, PA (US); Philip Pitis, North Wales, PA (US); Liang Lu, Hockessin, DE (US); and Andrew Paul Combs, Kennett Square, PA (US)
Assigned to Prelude Therapeutics Incorporated, Wilmington, DE (US)
Filed by Prelude Therapeutics, Incorporated, Wilmington, DE (US)
Filed on Jun. 9, 2021, as Appl. No. 17/343,341.
Claims priority of provisional application 63/036,811, filed on Jun. 9, 2020.
Prior Publication US 2022/0033409 A1, Feb. 3, 2022
Int. Cl. C07D 401/12 (2006.01); A61K 31/50 (2006.01); A61P 35/00 (2006.01); C07D 487/14 (2006.01); C07D 519/00 (2006.01)
CPC C07D 487/14 (2013.01) [C07D 519/00 (2013.01)] 18 Claims
 
1. A compound of Formula IA-7 or IA-8:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt 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(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—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;
n=0 to 3;
W is —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, C3-8 cyclcoalkyl, or C3-8 heterocyclcoalkyl;
X is —CH2—, or NH; or, if R1 is attached to X, then X is —CH— or N; and Q is —CH2—, —(CH2)2—, —C(O)—, —CH2C(O)—, —S(O)—, —S(O)2—, —CH2S(O)2—, or —CH2S(O)—;
R9 is —CN or

OG Complex Work Unit Chemistry
V is H or F;
R4 is H, D, haloalkyl, alkyl, cycloalkyl, heterocycloalkyl, —CORd, or —CONRe1Re2;
R7 is H, D, alkyl, cycloalkyl, or haloalkyl, Rd is H, or alkyl;
each Re1 and Re2 is independently H, D, alkyl,
or Re1 and Re2 together with the nitrogen atom to which they are attached form a 4-7 membered heterocyclyl.