US 12,441,754 B2
Galactoside inhibitor of galectins
Fredrik Zetterberg, Askim (SE)
Assigned to GALECTO BIOTECH AB, Copenhagen (DK)
Appl. No. 17/624,383
Filed by GALECTO BIOTECH AB, Copenhagen (DK)
PCT Filed Jul. 3, 2020, PCT No. PCT/EP2020/068809
§ 371(c)(1), (2) Date Jan. 3, 2022,
PCT Pub. No. WO2021/001528, PCT Pub. Date Jan. 7, 2021.
Claims priority of application No. 19184144 (EP), filed on Jul. 3, 2019.
Prior Publication US 2023/0014870 A1, Jan. 19, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07H 19/056 (2006.01)
CPC C07H 19/056 (2013.01) 17 Claims
 
1. A D-galactopyranose compound of formula (1)

OG Complex Work Unit Chemistry
wherein
the pyranose ring is α-D-galactopyranose,
A1 is selected from the group consisting of

OG Complex Work Unit Chemistry
wherein the asterix * indicates the carbon atom of the heteroaromatic ring that is covalently attached to the triazole group of formula (1);
wherein R2 is selected from the group consisting of hydrogen, C1-6 alkyl, OH and halogen;
R3 is selected from the group consisting of hydrogen, C1-6 alkyl and halogen;
R4 is selected from the group consisting of OH, halogen and amino;
R5 is selected from the group consisting of hydrogen, C1-6 alkyl and halogen;
X is selected from S, SO, and SO2;
B1 is selected from:
a) a phenyl, optionally substituted with one or more groups selected from:
a halogen;
N-(2-oxa)-6-azaspiro [3.3]heptanyl;
C2-alkynyl;
CN;
—COOH;
COOC1-4 alkyl;
—CONR6R7, wherein R6 and R7 are independently selected from H, C1-3 alkyl, cyclopropyl, and iso-propyl, or R6 and R7 together with the nitrogen form a heterocycloalkyl;
C1-3 alkyl, optionally substituted with a F;
cyclopropyl, optionally substituted with a F;
isopropyl, optionally substituted with a F;
SC1-3 alkyl, 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;
NR8R9, wherein R8 and R9 are independently selected from H, C1-3 alkyl and isopropyl;
OH;
R10—CONH— wherein R10 is selected from C1-3 alkyl and cyclopropyl;
a phenyl; and
a heterocycle selected from imidazole, pyridine, tetrahydropyridine, pyrimidin, oxazol and thiazol;
b) a benzothiazolyl, optionally substituted with one or more groups selected from:
a halogen;
N-(2-oxa)-6-azaspiro [3.3]heptanyl;
C2-alkynyl;
CN;
—COOH;
COOC1-4 alkyl;
—CONR12R13, wherein R12 and R13 are independently selected from H, C1-3 alkyl, cyclopropyl, and iso-propyl or R12 and R13 together with the nitrogen form a heterocycloalkyl;
C1-3 alkyl, optionally substituted with a F;
cyclopropyl, optionally substituted with a F;
isopropyl, optionally substituted with a F;
SC1-3 alkyl, 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;
SC1-3 alkyl, optionally substituted with a F;
NR14R15, wherein R14 and R15 are independently selected from H, C1-3 alkyl and isopropyl;
OH;
A phenyl;
a heterocycle selected from imidazole, pyridine, tetrahydropyridine, pyrimidin, oxazol and thiazol; and
R16—CONH— wherein R16 is selected from C1-3 alkyl and cyclopropyl;
c) thiazolpyridyl, optionally substituted with one or more groups selected from:
a halogen;
N-(2-oxa)-6-azaspiro [3.3]heptanyl;
C2-alkynyl;
CN;
—COOH;
COOC1-4 alkyl;
—CONR12R13, wherein R12 and R13 are independently selected from H, C1-3 alkyl, cyclopropyl, and iso-propyl or R12 and R13 together with the nitrogen form a heterocycloalkyl;
C1-3 alkyl, optionally substituted with a F;
cyclopropyl, optionally substituted with a F;
isopropyl, optionally substituted with a F;
SC1-3 alkyl, 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;
SC1-3 alkyl, optionally substituted with a F;
NR14R15, wherein R14 and R15 are independently selected from H, C1-3 alkyl and isopropyl;
OH;
a phenyl;
a heterocycle selected from imidazole, pyridine, tetrahydropyridine, pyrimidin, oxazol and thiazol; and
R16—CONH— wherein R16 is selected from C1-3 alkyl and cyclopropyl;
d) a pyridinyl, optionally substituted with one or more groups selected from:
a halogen;
N-(2-oxa)-6-azaspiro [3.3]heptanyl;
C2-alkynyl;
CN;
—COOH;
COOC1-4 alkyl;
—CONR12R13, wherein R12 and R13 are independently selected from H, C1-3 alkyl, cyclopropyl, and iso-propyl or R12 and R13 together with the nitrogen form a heterocycloalkyl;
C1-3 alkyl, optionally substituted with a F;
cyclopropyl, optionally substituted with a F;
isopropyl, optionally substituted with a F;
SC1-3 alkyl, 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;
SC1-3 alkyl, optionally substituted with a F;
NR14R15, wherein R14 and R15 are independently selected from H, C1-3 alkyl and isopropyl;
OH;
a phenyl;
a heterocycle selected from imidazole, pyridine, tetrahydropyridine, pyrimidin, oxazol and thiazol; and
R16—CONH— wherein R16 is selected from C1-3 alkyl and cyclopropyl;
R1 is H or OC1-6 alkyl optionally substituted with one or more halogen, phenyl, and phenyl substituted with one or more groups selected from OH and halogen; or
a pharmaceutically acceptable salt or solvate thereof.