US 12,410,207 B2
Galactoside inhibitor of galectins
Fredrik Zetterberg, Askim (SE); and Kristoffer Peterson, Lund (SE)
Assigned to GALECTO BIOTECH AB, Copenhagen (DK)
Appl. No. 17/624,663
Filed by GALECTO BIOTECH AB, Copenhagen (DK)
PCT Filed Jul. 3, 2020, PCT No. PCT/EP2020/068831
§ 371(c)(1), (2) Date Jan. 4, 2022,
PCT Pub. No. WO2021/004538, PCT Pub. Date Jan. 7, 2021.
Claims priority of application No. 19184150 (EP), filed on Jul. 3, 2019; application No. 20159106 (EP), filed on Feb. 24, 2020; and application No. 20168148 (EP), filed on Apr. 6, 2020.
Prior Publication US 2022/0281909 A1, Sep. 8, 2022
Int. Cl. C07H 19/052 (2006.01); C07H 19/24 (2006.01)
CPC C07H 19/052 (2013.01) [C07H 19/24 (2013.01)] 16 Claims
 
1. A D-galactopyranose compound of formula (1)

OG Complex Work Unit Chemistry
wherein
the pyranose ring is α-D-galactopyranose,
A1 is R1—Z,
wherein
Z is a five membered heterocycle having at least one heteroatom selected from O, S, and N, except 1,2,3-triazole and is attached to the α-D-galactopyranose;
R1 is selected from a) an aryl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR6aR7a, wherein R6a and R7a are independently selected from H, C1-3 alkyl, cyclopropyl, and iso-propyl, or R6a and R7a together with the nitrogen may form a heterocycloalkyl; C1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR8aR9a, wherein R8a and R9a are independently selected from H, C1-3 alkyl and isopropyl; OH; and R10a—CONH— wherein R10a is selected from C1-3 alkyl and cyclopropyl; and b) a heterocycle, optionally substituted with a group selected from a halogen; a spiro heterocycle; CN; —COOH; —CONR12aR13a, wherein R12a and R13a are independently selected from H, C1-3 alkyl, cyclopropyl, and iso-propyl; C1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR14aR15a, wherein R14a and R15a are independently selected from H, C1-3 alkyl, and cyclopropyl; C(═O)—R21a, wherein R21a is selected from H and C1-3 alkyl; OH; and R16a—CONH— wherein R16a is selected from C1-3 alkyl and cyclopropyl;
X is selected from S, SO, SO2, O, C═O, and CR2bR3b wherein R2b and R3b are independently selected from hydrogen, OH, or halogen;
B1 is selected from a) a C1-6 alkyl or branched C3-6 alkyl substituted with a five or six membered heteroaromatic ring, optionally substituted with a substituent selected from CN, a halogen, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R4b—CONH— wherein R4b is selected from C1-3 alkyl and cyclopropyl; or a C1-6 alkyl substituted with a phenyl, optionally substituted with a substituent selected from CN, a halogen, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R5b—CONH— wherein R5b is selected from C1-3 alkyl and cyclopropyl; b) an aryl, optionally substituted with a group selected from a halogen; CN; a spiro heterocycle; C2-alkynyl; —COOH; —CONR6bR7b, wherein R6b and R7b are independently selected from H, C1-3 alkyl, cyclopropyl, and iso-propyl, or R6b and R7b together with the nitrogen may form a heterocycloalkyl; C1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR8bR9b, wherein R8b and R9b are independently selected from H, C1-3 alkyl and isopropyl; OH; a heterocycle optionally substituted with a C1-3 alkyl optionally substituted with a OH; and R10b—CONH— wherein R10b is selected from C1-3 alkyl and cyclopropyl; c) a C5-7 cycloalkyl, optionally substituted with a substituent selected from a halogen, C2-alkynyl, CN, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R11b—CONH— wherein R11b is selected from C1-3 alkyl and cyclopropyl; d) a heterocycle, optionally substituted with a group selected from a halogen; a spiro heterocycle; C2-alkynyl; CN; —COOH; —CONR12bR13b, wherein R12b and R13b are independently selected from H, C1-3 alkyl, cyclopropyl, and iso-propyl; C1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR14bR15b, wherein R14b and R15b are independently selected from H, C1-3 alkyl and isopropyl; OH; a heterocycle optionally substituted with a C1-3 alkyl optionally substituted with a OH; and R16b—CONH— wherein R16b is selected from C1-3 alkyl and cyclopropyl; e) a C1-6 alkyl or branched C3-6 alkyl; and f) C2-6 alkynyl;
R50 is selected from the group consisting of a) H, b) OH, c) OC1-6 alkyl optionally substituted with one or more halogen, phenyl, phenyl substituted with one or more groups selected form OH and halogen, CN, OR17b, NR18bR19b, and CONH2, wherein R17b is selected from the group consisting of H, CN, a halogen, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R20b—CONH— wherein R20b is selected from C1-3 alkyl and cyclopropyl, R18b is selected from the group consisting of H, CN, a halogen, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R21b—CONH— wherein R21b is selected from C1-3 alkyl and cyclopropyl, and R19b is selected from the group consisting of H, CN, a halogen, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R22b—CONH— wherein R22b is selected from C1-3 alkyl and cyclopropyl, d) branched OC3-6 alkyl optionally substituted with one or more halogen, CN, OR23b, NR24bR25b, and CONH2, wherein R23b is selected from the group consisting of H, CN, a halogen, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R26b—CONH— wherein R26b is selected from C1-3 alkyl and cyclopropyl, R24b is selected from the group consisting of H, CN, a halogen, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R27b—CONH— wherein R27b is selected from C1-3 alkyl and cyclopropyl, and R25b is selected from the group consisting of H, CN, a halogen, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R28—CONH— wherein R28 is selected from C1-3 alkyl and cyclopropyl, and e) cyclic OC3-6 alkyl optionally substituted with one or more halogen, CN, OR29, NR30R31 or CONH2, wherein R29 is selected from the group consisting of H, CN, a halogen, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R32—CONH— wherein R32 is selected from C1-3 alkyl and cyclopropyl, R30 is selected from the group consisting of H, CN, a halogen, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R33—CONH— wherein R33 is selected from C1-3 alkyl and cyclopropyl, and R31 is selected from the group consisting of H, CN, a halogen, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R34—CONH— wherein R34 is selected from C1-3 alkyl and cyclopropyl; or
a pharmaceutically acceptable salt or solvate thereof.