US 12,291,548 B2
Compounds, compositions, and methods for the treatment of disease
Radhakrishnan P. Iyer, Shrewsbury, MA (US); Geeta Meher, Milford, MA (US); Sreerupa Challa, Shrewsbury, MA (US); and Shenghua Zhou, Shrewsbury, MA (US)
Assigned to Sperovie Biosciences, Inc., Hopkinton, MA (US)
Appl. No. 17/258,914
Filed by Sperovie Biosciences, Inc., Hopkinton, MA (US)
PCT Filed Jul. 8, 2019, PCT No. PCT/US2019/040811
§ 371(c)(1), (2) Date Jan. 8, 2021,
PCT Pub. No. WO2020/014127, PCT Pub. Date Jan. 16, 2020.
Claims priority of provisional application 62/695,997, filed on Jul. 10, 2018.
Prior Publication US 2021/0309692 A1, Oct. 7, 2021
Int. Cl. C07H 21/02 (2006.01); A61K 31/7084 (2006.01); A61K 45/06 (2006.01)
CPC C07H 21/02 (2013.01) [A61K 31/7084 (2013.01); A61K 45/06 (2013.01)] 20 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
Z is either S or O;
B1 is a natural purinyl nucleobase and B2 is a natural pyrimidinyl nucleobase or B2 is a natural purinyl nucleobase and B1 is a natural pyrimidinyl nucleobase;
each of X1 and X2 is independently O or S;
each of Y1 and Y2 is independently O, S, or NR5;
L1 is absent, C1-C6 alkyl or C1-C6 heteroalkyl and L2 is C1-C6 alkyl or C1-C6 heteroalkyl, wherein each alkyl and heteroalkyl is optionally substituted with R6; or L1 is C1-C6 alkyl or C1-C6 heteroalkyl, and L2 is absent, C1-C6 alkyl, or C1-C6 heteroalkyl, wherein each alkyl and heteroalkyl is optionally substituted with R6;
each of R1 and R2 is independently hydrogen, halo, —CN, C1-C20 alkyl, or OR7;
each of R3 and R4 is independently hydrogen, C1-C20 alkyl, C1-C20 heteroalkyl, OC(O)OC1-C20 alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each alkyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R8;
R5 is hydrogen or C1-C20 alkyl;
R6 is halo, —CN, C1-C20 alkyl, OR7, oxo, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R9;
R7 is hydrogen, C1-C20 alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R9;
each R8 is independently C1-C20 alkyl, C1-C20 heteroalkyl, C(O)—C1-C20 alkyl, OC(O)—C1-C20 alkyl, C(O)O—C1-C20 alkyl, OC(O)O—C1-C20 alkyl, C(O)N(R5)—C1-C20 alkyl, N(R5)C(O)—C1-C20 alkyl, OC(O)N(R5)—C1-C20 alkyl, O-aryl, O-heteroaryl, C(O)-aryl, C(O)-heteroaryl, OC(O)-aryl, C(O)O-aryl, OC(O)-heteroaryl, C(O)O-heteroaryl, C(O)N(R5)-aryl, C(O)N(R5)-heteroaryl, N(R5)C(O)-aryl, N(R5)2C(O)-aryl, N(R5)C(O)-heteroaryl, or S(O)2N(R5)-aryl, wherein each alkyl, heteroalkyl, aryl, and heteroaryl is optionally substituted by one or more R9; and
each R9 is independently C1-C20 alkyl, O—C1-C20 alkyl, C1-C20 heteroalkyl, halo, —CN, OH, oxo, aryl, heteroaryl, O-aryl, or O-heteroaryl.