Galactoside inhibitor of galectins

A D-galactopyranose compound of formula (1)

• wherein
• the pyranose ring is α-D-galactopyranose,
• A1 is selected from
• wherein Het1 is selected from a five or six membered heteroaromatic ring, optionally substituted with a group selected from Br;
• F;
• Cl;
• I;
• CN;
• NR19R20, wherein R19 and R20 are independently selected from H, C1-3 alkyl, cyclopropyl, iso-propyl, —C(═O)—R21, wherein R21 is selected from H and C1-3 alkyl;
• C1-3 alkyl, optionally substituted with a F;
• cyclopropyl, optionally substituted with a F;
• iso-propyl, optionally substituted with a F;
• O-cyclopropyl optionally substituted with a F;
• O-isopropyl optionally substituted with a F;
• OC1-3 alkyl optionally substituted with a F;
• and SC1-3 alkyl optionally substituted with a F;
• wherein R1-R5 are independently selected from H, CN, NH2, Br, Cl, I, F, methyl optionally substituted with a F, SCH3 optionally substituted with a F, and OCH3 optionally substituted with a F;
• wherein R6 is selected from C1-6 alkyl optionally substituted with a halogen, branched C3-6 alkyl and C3-7 cycloalkyl;
• wherein R7 is selected from a five or six membered heteroaromatic ring, optionally substituted with a group selected from Br, F, Cl, methyl optionally substituted with a F, and OCH3 optionally substituted with a F, and a phenyl optionally substituted with a group selected from Br, F, Cl, methyl optionally substituted with a F, and OCH3 optionally substituted with a F;
• wherein R8-R12 are independently selected from H, F, methyl optionally substituted with a F, and OCH3 optionally substituted with a F;
• wherein R13 is a five or six membered heteroaromatic ring optionally substituted with a group selected from H, OH, F, methyl optionally substituted with a F, and OCH3 optionally substituted with a F, or an aryl, optionally substituted with a group selected from H, OH, F, methyl optionally substituted with a F, and OCH3 optionally substituted with a F;
• X is selected from S, SO, SO2, O, C═O, and CR7R8 wherein R7 and R8 are independently selected from hydrogen, OH, or halogen;
• wherein R27 is selected from a C1-6 alkyl, branched C3-6 alkyl, C1-6 alkoxy and branched C3-6 alkoxy;
• 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 R14—CONH— wherein R14 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 R15—CONH— wherein R15 is selected from C1-3 alkyl and cyclopropyl;
• b) an aryl, optionally substituted with a group selected from a halogen;
• CN;
• —COOH;
• —CONR22R23, wherein R22 and R23 are independently selected from H, C1-3 alkyl, cyclopropyl, and iso-propyl, or R22 and R23 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;
• NR28R29, wherein R28 and R29 are independently selected from H, C1-3 alkyl and isopropyl;
• OH;
• and R16—CONH— wherein R16 is selected from C1-3 alkyl and cyclopropyl;
• c) a C5-7 cycloalkyl, optionally substituted with a substituent selected from a halogen, CN, methyl optionally substituted with a F, OCH3 optionally substituted with a F, OCH2CH3 optionally substituted with a F, OH, and R17—CONH— wherein R17 is selected from C1-3 alkyl and cyclopropyl;
• and d) a heterocycle, optionally substituted with a group selected from a halogen;
• a spiro heterocycle;
• CN;
• —COOH;
• —CONR24R25, wherein R24 and R25 are independently selected from H, C1-3 alkyl, cyclopropyl, and iso-propyl or R24 and R25 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;
• NR30R31, wherein R30 and R31 are independently selected from H, C1-3 alkyl and isopropyl;
• OH;
• R18—CONH— wherein R18 is selected from C1-3 alkyl and cyclopropyl;
• a pyrimidinyl 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 R71—CONH— wherein R71 is selected from C1-3 alkyl and cyclopropyl;
• a pyridinyl 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 R72—CONH— wherein R72 is selected from C1-3 alkyl and cyclopropyl;
• a tetrahydropyridinyl 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 R73—CONH— wherein R73 is selected from C1-3 alkyl and cyclopropyl;
• a pyrrolinyl 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 R74—CONH— wherein R74 is selected from C1-3 alkyl and cyclopropyl;
• an oxazolyl 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 R75—CONH— wherein R75 is selected from C1-3 alkyl and cyclopropyl;
• a thiazolyl 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 R76—CONH— wherein R76 is selected from C1-3 alkyl and cyclopropyl;
• and a C2-4 alkynyl, or e) a C1-6 alkyl or branched C3-6 alkyl;
• R50 is selected from the group consisting of a) C1-6 alkyl optionally substituted with one or more halogen, CN, OR51, NR52R53, and CONH2, wherein R51 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 R54—CONH— wherein R54 is selected from C1-3 alkyl and cyclopropyl, R52 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 R55—CONH— wherein R55 is selected from C1-3 alkyl and cyclopropyl, and R53 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 R56—CONH— wherein R56 is selected from C1-3 alkyl and cyclopropyl, b) branched C3-6 alkyl optionally substituted with one or more halogen, CN, OR57, NR58R59, and CONH2, wherein R57 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 R60—CONH— wherein R60 is selected from C1-3 alkyl and cyclopropyl, R58 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 R61—CONH— wherein R61 is selected from C1-3 alkyl and cyclopropyl, and R59 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 R62—CONH— wherein R62 is selected from C1-3 alkyl and cyclopropyl, and c) cyclic C3-6 alkyl optionally substituted with one or more halogen, CN, OR63, NR64R65, and CONH2, wherein R63 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 R66—CONH— wherein R66 is selected from C1-3 alkyl and cyclopropyl, R64 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 R67—CONH— wherein R67 is selected from C1-3 alkyl and cyclopropyl, and R65 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 R68—CONH— wherein R68 is selected from C1-3 alkyl and cyclopropyl;
• or
• a pharmaceutically acceptable salt or solvate thereof.