US 12,473,283 B2
Compounds and their use
Vincent Gerusz, Neuvecelle (FR); Juan Bravo, Epalinges (CH); Heinz Pauls, Ontario (CA); Judd Berman, Encinitas, CA (US); and Terry Finn, Geneva (CH)
Assigned to Debiopharm International S.A., Lausanne (CH)
Appl. No. 17/786,727
Filed by Debiopharm International S.A., Lausanne (CH)
PCT Filed Dec. 18, 2020, PCT No. PCT/EP2020/087308
§ 371(c)(1), (2) Date Jun. 17, 2022,
PCT Pub. No. WO2021/123372, PCT Pub. Date Jun. 24, 2021.
Claims priority of application No. PCT/IB2019/061119 (WO), filed on Dec. 19, 2019.
Prior Publication US 2023/0159519 A1, May 25, 2023
Int. Cl. C07D 471/04 (2006.01); A61P 31/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 31/04 (2018.01); C07D 519/00 (2013.01)] 22 Claims
 
1. A compound of formula (I)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable prodrug, salt and/or solvate thereof, wherein
LHS is selected from the group consisting of LHSa and LHSb

OG Complex Work Unit Chemistry
wherein, the asterisk (*) marks the point of attachment;
Y is selected from the group consisting of CH2, NH, and NRd;
Q1 is selected from the group consisting of O, S, NH and N—C1-4-alkyl;
R0 is selected from the group consisting of CH3 and Cl, or alternatively R0 together with R14 form a heterocycle comprising the N to which R14 is attached and having 5 to 8 ring members, wherein preferably the only heteroatom in said ring is the N to which R14 is attached;
R1 is selected from the group consisting of H, F, Cl, Br, I, C1-4-alkyl, OR5, CN, NR5R6, CO—NR5R6, C1-4-alkylene-NR5R6, C1-4-alkylene-OR5, NH—CO—C1-4-alkylene-R5, NH—CO—NR5R6, NH—COOR5, NHSO2—C1-4-alkylene-R5, C3-6-cycloalkyl, phenyl, and a heterocyclic group having 5 or 6 ring members and 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein said C1-4-alkyl, cycloalkyl, phenyl, or heterocyclic group may optionally be substituted with 1-3 R7 groups;
R2 is selected from the group consisting of H, F, Cl, Br, I, C1-4-alkyl, OR5, C1-4-alkylene-OR5, CN, NR5R6, CO—NR5R6, C1-4-alkylene-NR5R6, C3-6-cycloalkyl, phenyl, and a heterocyclic group having 5 or 6 ring members and 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein said C1-4-alkyl, cycloalkyl, phenyl, or heterocyclic group may optionally be substituted with 1-3 R7 groups;
R3 is selected from the group consisting of H, F, Cl, Br, I, CN, C1-4-alkyl, O—C1-4 alkyl, OH, NH2, NHC1-4-alkyl, and S—C1-4-alkyl;
R3a, R3b and R3c are independently selected from the group consisting of H, F, Cl, Br, I, CN, C1-4-alkyl, O—C1-4-alkyl, OH, NH2, NHC1-4-alkyl, and S—C1-4-alkyl;
R4 is selected from the group consisting of H, F, Cl, Br, I, C1-4-alkyl, OR5, CN, COR10, phenyl, OH, NH2, S—C1-4-alkyl, NR5R6, and a heterocyclic group having 5 or 6 ring members and 1, 2 or 3 heteroatoms independently selected from N, O and S;
R5 and R6 are independently selected from is selected from the group consisting of H, COR10, C1-4-alkyl, C3-6-cycloalkyl, SO2R7, phenyl, and a heterocyclic group having 5 or 6 ring members and 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein said cycloalkyl, phenyl, or heterocyclic group may optionally be substituted with 1-3 R7 groups;
R7 is selected from the group consisting of H, F, I, Br, Cl, O, C1-4-alkyl, CONH2, OH, NH2, O—C1-4-alkyl, NH—C1-4-alkyl, N(C1-4-alkyl)2, C1-4-alkylene-OH, and C1-4-alkylene-NH2, NO2, CN, C2-4-alkenyl, C2-4-alkynyl, C2-4-alkynylene-OH, C2-4-alkynylene-NH2, SO2CH3, and O—C1-4-alkylene-OH;
R8 and R9 are independently selected from the group consisting of H, C1-4-alkyl, C1-4-alkyl-F, CN, OH, NH2, O—C1-4-alkyl, NH—C1-4-alkyl, N(C1-4-alkyl)2, C1-4-alkylene-OH, and C1-4-alkylene-NH2;
R10 is selected from the group consisting of H, C1-4-alkyl, C1-4-alkyl-F, C1-4-alkylene-OH, and C1-4-alkylene-NH2;
R11 and R12 are independently selected from the group consisting of H, Rd, C1-4-alkyl, CO—C1-4-alkyl, SO2(C1-4-alkyl)1, C1-4-alkyl-F, C1-4-alkylene-OH, and C1-4-alkylene-NH2, or alternatively, R11 and R12 together with the N to which they are attached form a heterocyclic group having 4 to 9 ring members and 1, 2 or 3 heteroatoms independently selected from N, O and S or form a heterocyclic spiro group having 7 to 11 ring members and 1, 2 or 3 heteroatoms independently selected from N, O and S, wherein said heterocyclic or heterocyclic spiro group may be substituted with 1-3 R7 groups;
R13 is selected from the group consisting of H or Rd;
R14 is CH3, or alternatively R14 together with R0 of LHSa or LHSb form a heterocycle comprising the N to which R14 is attached and having 5 to 8 ring members, wherein preferably the only heteroatom in said ring is the N to which R14 is attached;
and,
Rd is selected from the group consisting of —PO3Re2, —CH2—OPO3Re2, wherein Re is selected from the group consisting of H and a cation suitable for forming a pharmaceutically acceptable salt.