GALACTOSIDE INHIBITOR OF GALECTINS

Abstract

A compound of the general formula I or II. The compound of formula I or II is suitable for use in a method for treating a disorder relating to the binding of a galectin, such as galectin-3 to a ligand in a mammal, such as a human. Furthermore, a method for treatment of a disorder relating to the binding of a galectin, such as galectin-3 to a ligand in a mammal, such as a human.

Claims

1-18. (canceled)

19. A compound of formula (I) ##STR00111## wherein the pyranose ring is α- or β-D-galactopyranose (as indicated by wavy line); wherein: A.sup.1 is selected from the group consisting of i) an aryl; ii) an aryl substituted with at least one from the group consisting of a halogen; CN; C.sub.2-6 alkenyl; C.sub.2-6 alkynyl; carboxyl; C.sub.1-6 alkoxy; C.sub.1-6 thioalkyl; C.sub.1-6 alkyl; nitro; thio; C.sub.1-6 alkylthio; amino; hydroxy; C.sub.1-6 carbonyl; an amino; and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; iii) a C.sub.1-6 alkoxy; iv) a C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen; a C.sub.1-6 alkyl; a heteroaryl; a heteroaryl substituted with at least one from the group consisting of halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, amino, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted with at least one halogen, a five or six membered heteroaromatic ring, a five or six membered heteroaromatic ring substituted with at least one from the group consisting of halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one halogen, C.sub.1-6 alkoxy, and C.sub.1-6 alkoxy substituted with at least one halogen, an aryl, and an aryl substituted with at least one from the group consisting of halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one halogen, C.sub.1-6 alkoxy, and C.sub.1-6 alkoxy substituted with at least one halogen; an amino; and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; v) a C.sub.1-6 alkylamino; vi) a C.sub.1-6 alkylamino substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; vii) a heteroaryl; viii) a heteroaryl substituted with at least one from the group consisting of a halogen; CN; C.sub.2-6 alkenyl; C.sub.2-6 alkynyl; carboxyl; C.sub.1-6 alkoxy; C.sub.1-6 thioalkyl; an amino; an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; an aryl; an aryl substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a heteroaryl; a heteroaryl substituted with at least one from the group consisting of halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkoxy, and C.sub.3-7 cycloalkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a C.sub.1-6 carbonyl; a C.sub.1-6 carbonyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; ix) a heterocycle; x) a heterocycle substituted with at least one from the group consisting of halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkoxy, and C.sub.3-7 cycloalkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a C.sub.1-6 carbonyl; a C.sub.1-6 carbonyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; xi) a C.sub.1-6 alkyl; xii) a C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen; C.sub.1-6 alkoxy; C.sub.1-6 alkyl; C.sub.3-7 cycloalkyl; nitro; thio; C.sub.1-6 alkylthio; amino; hydroxy; and C.sub.1-6 carbonyl; xiii) a C.sub.1-6 carbonyl; xiv) a C.sub.1-6 carbonyl substituted with at least one from the group consisting of a C.sub.1-6 alkyl; a C.sub.2-6 alkenyl; an aryl; a heteroaryl; and a heterocycle; xv) a C.sub.1-6 alkyl-CONH—; xvi) a C.sub.1-6 alkyl-CONH— substituted on one or more alkyl carbon with at least one from the group consisting of a heteroaryl; a heteroaryl substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkoxy substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; an aryl; and an aryl substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkoxy substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; X.sup.1 is selected from the group consisting of O, S, SO, SO.sub.2, C═O, amino, amino substituted with a C.sub.1-6 alkyl, and CR′R″ wherein R′ and R″ are independently selected from hydrogen, OH, or halogen; B.sup.1 is selected from the group consisting of a) a C.sub.1-6 alkyl, b) a C.sub.1-6 alkyl substituted with at least one from the group consisting of a five or six membered heteroaromatic ring; a five or six membered heteroaromatic ring substituted with at least one from the group consisting of cyano, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, hydroxy and C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted with at least one from the group consisting of halogen, hydroxy and C.sub.1-6 alkyl, hydroxy, and R.sup.#—CONH— wherein R.sup.# is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; an aryl; and an aryl substituted with at lest one from the group consisting of cyano, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, hydroxy and C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted with at least one from the group consisting of halogen, hydroxy and C.sub.1-6 alkyl, hydroxy, and R.sup.¤—CONH— wherein R.sup.¤ is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; c) an aryl; d) an aryl substituted with at least one from the group consisting of halogen; cyano; hydroxy; carboxyl; carboxamid; carboxamid substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.3-6 cycloalkyl; C.sub.1-6 alkyl; C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.&—CONH— wherein R.sup.& is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.%—CONH— wherein R.sup.% is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 alkoxy; C.sub.1-6 alkoxy substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.§—CONH— wherein IV is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.3-6 cycloalkoxy; C.sub.3-6 cycloalkoxy substituted with at least one from the group consisting of halogen, hydroxy, and R*—CONH— wherein R* is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; amino; amino substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; and R**—CONH— wherein R** is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; e) a C.sub.4-10 cycloalkyl, f) a C.sub.4-10 cycloalkyl substituted with at least one from the group consisting of cyano, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, hydroxy and C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted with at least one from the group consisting of halogen, hydroxy and C.sub.1-6 alkyl, hydroxy, and R.sup.##—CONH— wherein R.sup.## is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; and g) a heterocycle substituted with at least one from the group consisting of halogen; cyano; hydroxy; carboxyl; carboxamid; carboxamid substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.3-6 cycloalkyl; C.sub.1-6 alkyl; C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.&&—CONH— wherein R.sup.&& is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.%%—CONH— wherein R.sup.%%is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 alkoxy; C.sub.1-6 alkoxy substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.§§ —CONH— wherein R.sup.§§ is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.3-6 cycloalkoxy; C.sub.3-6 cycloalkoxy substituted with at least one from the group consisting of halogen, hydroxy, and Ra—CONH— wherein W; is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; amino; amino substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; R.sup.aa—CONH— wherein R.sup.aa is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; a heteroaryl substituted with at least one from the group consisting of a halogen; an amino; an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; an aryl; an aryl substituted with at least one from the group consisting of a halogen, cyano, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a heteroaryl; a heteroaryl substituted with at least one from the group consisting of halogen, cyano, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkoxy, and C.sub.3-7 cycloalkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a C.sub.1-6 carbonyl; and a C.sub.1-6 carbonyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; and R.sup.1 is an acid isostere having one or two lone pairs or an acidic proton, or both; or a pharmaceutically acceptable salt or solvate thereof.

20. The compound of claim 19 having formula II ##STR00112## wherein the pyranose ring is α-D-galactopyranose, wherein: A.sup.2 is selected from ##STR00113## wherein Het.sup.1a is selected from a five or six membered heteroaromatic ring, optionally substituted with a group selected from Br; F; Cl; CN; NR.sup.19aR.sup.20a, wherein R.sup.19a and R.sup.29a are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, iso-propyl, —C(═O)—R.sup.21a, wherein R.sup.21a is selected from H and C.sub.1-3 alkyl; C.sub.1-3 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; and OC.sub.1-3 alkyl optionally substituted with a F; wherein R.sup.1a—R.sup.5a are independently selected from H, CN, NH.sub.2, Cl, F, methyl optionally substituted with a F, and OCH.sub.3 optionally substituted with a F; wherein R.sup.6a is selected from C.sub.1-6 alkyl optionally substituted with a halogen, branched C.sub.3-6 alkyl and C.sub.3-7 cycloalkyl; wherein R.sup.7a 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 OCH.sub.3 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 OCH.sub.3 optionally substituted with a F; wherein R.sup.8a—R.sup.12a are independently selected from H, F, methyl optionally substituted with a F, and OCH.sub.3 optionally substituted with a F; wherein R.sup.13a 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 OCH.sub.3 optionally substituted with a F, or an aryl, such as phenyl or naphthyl, optionally substituted with a group selected from H, OH, F, methyl optionally substituted with a F, and OCH.sub.3 optionally substituted with a F; X.sup.1 is selected from S, SO, SO.sub.2, O, C═O, and CR.sup.32aR.sup.33a wherein R.sup.32a and R.sup.33a are independently selected from hydrogen, OH, or halogen; wherein R.sup.27a is selected from a C.sub.1-6 alkyl, branched C.sub.3-6 alkyl, C.sub.1-6 alkoxy and branched C.sub.3-6 alkoxy; B.sup.2 is selected from a) a C.sub.1-6 alkyl or branched C.sub.3-6 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, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH3 optionally substituted with a F, OH, and R.sup.14a—CONH— wherein R.sup.14a is selected from C.sub.1-3 alkyl and cyclopropyl; or a C.sub.1-6 alkyl substituted with a phenyl, optionally substituted with a substituent selected from CN, a halogen, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.15a—CONH— wherein R.sup.15a is selected from C.sub.1-3 alkyl and cyclopropyl; b) an aryl, such as phenyl or naphthyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.22aR.sup.23a, wherein R.sup.22a and R.sup.23a are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.28aR.sup.29a, wherein R.sup.28a and R.sup.29a are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.16a—CONH— wherein R.sup.16a is selected from C.sub.1-3 alkyl and cyclopropyl; c) a C.sub.5-7 cycloalkyl, optionally substituted with a substituent selected from a halogen, CN, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.17a—CONH— wherein R.sup.17a is selected from C.sub.1-3 alkyl and cyclopropyl; and d) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.24aR.sup.25a, wherein R.sup.24a and R.sup.25a are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.30aR.sup.31a, wherein R.sup.30a and R.sup.31a are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.18a—CONH— wherein R.sup.18a is selected from C.sub.1-3 alkyl and cyclopropyl; e) a C.sub.1-6 alkyl or branched C.sub.3-6 alkyl; and R.sup.1 is an acid isostere having one or two lone pairs or an acidic proton, or both; or a pharmaceutically acceptable salt or solvate thereof.

21. The compound of claim 19 having formula II ##STR00114## wherein the pyranose ring is α-D-galactopyranose, wherein: A.sup.2 is selected from ##STR00115## wherein Het.sup.1b is selected from a pyridinyl, optionally substituted with a group selected from H, CN, Br, Cl, I, F, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, and SCH.sub.3 optionally substituted with a F; or a pyrimidyl, optionally substituted with a group selected from H, CN, Br, Cl, I, F, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, and SCH.sub.3 optionally substituted with a F; wherein R.sup.1b—R.sup.5b are independently selected from a group consisting of H, CN, Br, Cl, I, F, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, and SCH.sub.3 optionally substituted with a F; X.sup.1 is selected from S, SO, and SO.sub.2; B.sup.2 is selected from a) a C.sub.1-6 alkyl or branched C.sub.3-6 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, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.14b—CONH— wherein R.sup.14b is selected from C.sub.1-3 alkyl and cyclopropyl; or a C.sub.1-6 alkyl substituted with a phenyl, optionally substituted with a substituent selected from CN, a halogen, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.15b—CONH— wherein R.sup.15b is selected from C.sub.1-3 alkyl and cyclopropyl; b) an aryl, such as phenyl or naphthyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.22bR.sup.23b, wherein R.sup.22b and R.sup.23b are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.28bR.sup.29b, wherein R.sup.28b and R.sup.29b are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.16b—CONH— wherein R.sup.16b is selected from C.sub.1-3 alkyl and cyclopropyl; c) a C.sub.5-7 cycloalkyl, optionally substituted with a substituent selected from a halogen, CN, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.17b—CONH— wherein R.sup.171) is selected from C.sub.1-3 alkyl and cyclopropyl; and d) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.24bR.sup.25b, wherein R.sup.24b and R.sup.25b are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.30bR.sup.31b, wherein R.sup.30b and R.sup.31b are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.18b—CONH— wherein R.sup.18b is selected from C.sub.1-3 alkyl and cyclopropyl; e) a C.sub.1-6 alkyl or branched C.sub.3-6 alkyl; and R.sup.1 is an acid isostere having one or two lone pairs or an acidic proton, or both; or a pharmaceutically acceptable salt or solvate thereof.

22. The compound of claim 21, wherein A.sup.2 is ##STR00116## Wherein R.sup.1b—R.sup.5b are independently selected from a group consisting of H, CN, Br, Cl, I, F, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, and SCH.sub.3 optionally substituted with a F; X.sup.1 is S; B.sup.2 is selected from b) a phenyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.22bR.sup.23b, wherein R.sup.22b and R.sup.23b are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.28bR.sup.29b, wherein R.sup.28b and R.sup.29b are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.16b—CONH— wherein R.sup.16b is selected from C.sub.1-3 alkyl and cyclopropyl; d) a heteroaryl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.24bR.sup.25b, wherein R.sup.24b and R.sup.25b are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.30bR.sup.31b, wherein R.sup.30b and R.sup.31b are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.18b—CONH— wherein R.sup.18b is selected from C.sub.1-3 alkyl and cyclopropyl; and R.sup.1 is an acid isostere having one or two lone pairs or an acidic proton, or both; or a pharmaceutically acceptable salt or solvate thereof.

23. The compound of claim 22, wherein A.sup.2 is ##STR00117## wherein R.sup.1b—R.sup.5b are independently selected from a group consisting of H, Cl and F; X.sup.1 is S; B.sup.2 is selected from b) a phenyl substituted with a halogen; and d) a heteroaryl substituted with a halogen; R.sup.1 is an acid isostere having one or two lone pairs or an acidic proton, or both; or a pharmaceutically acceptable salt or solvate thereof.

24. The compound of claim 23, wherein A.sup.2 is ##STR00118## wherein R.sup.1b and R.sup.5b are hydrogen, and at least one of R.sup.2b—R.sup.4b is independently selected from Cl and F and the rest is hydrogen; X.sup.1 is S; B.sup.2 is selected from b) a phenyl substituted with a Cl; and d) a pyridinyl substituted with a Br; R.sup.1 is an acid isostere having one or two lone pairs or an acidic proton, or both; or a pharmaceutically acceptable salt or solvate thereof.

25. The compound of claim 19 having formula II ##STR00119## wherein the pyranose ring is α-D-galactopyranose, A2 is ##STR00120## wherein Het.sup.1c is a five or six membered heteroaromatic ring selected from the group consisting of formulas 2 to 9: ##STR00121## wherein R.sup.2c to R.sup.23c and R.sup.27c are independently selected from H; halogen; OH; CN; SH; S—C.sub.1-3 alkyl; C.sub.1-3 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; OC.sub.1-3 alkyl optionally substituted with a F; NR.sup.24cR.sup.25c, wherein R.sup.24c is selected from H, and C.sub.1-3 alkyl, and R.sup.25c is selected from H, C.sub.1-3 alkyl, and COR.sup.26c, wherein R.sup.26c is selected from H, and C.sub.1-3 alkyl; X.sup.1 is selected from S, SO, SO.sub.2; B.sup.2 is selected from a) a C.sub.1-6 alkyl or branched C.sub.3-6 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, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.27#—CONH— wherein R.sup.27# is selected from C.sub.1-3 alkyl and cyclopropyl; or a C.sub.1-6 alkyl substituted with a phenyl, optionally substituted with a substituent selected from CN, a halogen, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.28c—CONH— wherein R.sup.28c is selected from C.sub.1-3 alkyl and cyclopropyl; b) an aryl, such as phenyl or naphthyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.29cR.sup.30c, wherein R.sup.29c and R.sup.30c are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.31cR.sup.32c, wherein R.sup.31c and R.sup.32c are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.33c—CONH—, wherein R.sup.33c is selected from C.sub.1-3 alkyl and cyclopropyl; c) a C.sub.5-7 cycloalkyl, optionally substituted with a substituent selected from a halogen, CN, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.34c—CONH— wherein R.sup.34c is selected from C.sub.1-3 alkyl and cyclopropyl; and d) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.35cR.sup.36c, wherein R.sup.35c and R.sup.36c are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.37cR.sup.38c, wherein R.sup.37c and R.sup.38c are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.39c—CONH— wherein R.sup.30c is selected from C.sub.1-3 alkyl and cyclopropyl; e) a C.sub.1-6 alkyl or branched C.sub.3-6 alkyl; and R.sup.1 is an acid isostere having one or two lone pairs or an acidic proton, or both; or a pharmaceutically acceptable salt or solvate thereof.

26. The compound of claim 19 having formula II ##STR00122## wherein the pyranose ring is α-D-galactopyranose, A.sup.2 is ##STR00123## wherein the pyranose ring is α-D-galactopyranose, Het.sup.1d is selected from the group consisting of ##STR00124## wherein R.sup.2d is selected from the group consisting of OH and halogen; R.sup.3d is selected from the group consisting of hydrogen, C.sub.1-6 alkyl and halogen; R.sup.4d is selected from the group consisting of OH and halogen; R.sup.5d is selected from the group consisting of hydrogen, C.sub.1-6 alkyl and halogen; X.sup.1 is S; B.sup.2 is selected from a) an aryl, such as phenyl or naphthyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.29dR.sup.30d, wherein R.sup.29d and R.sup.30d are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; SC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.31dR.sup.32d, wherein R.sup.31d and R.sup.32d are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.33d—CONH—, wherein R.sup.33d is selected from C.sub.1-3 alkyl and cyclopropyl; b) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.35dR.sup.36d, wherein R.sup.35d and R.sup.36d are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; SC.sub.1-3 alkyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.37dR.sup.38d, wherein R.sup.37d and R.sup.38d are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.39d—CONH— wherein R.sup.39d is selected from C.sub.1-3 alkyl and cyclopropyl; and R.sup.1 is an acid isostere having one or two lone pairs or an acidic proton, or both; or a pharmaceutically acceptable salt or solvate thereof.

27. The compound of claim 19, wherein R.sup.1 is selected from the group consisting of a) a phosphate, b) a sulphate, c) a C.sub.1-6 alkyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, C.sub.1-6 alkyl, and methylsulphonyl; a heterocycle, such as a heteroaryl or heterocycloalkyl, optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a —SO.sub.2—NHR.sup.3 wherein R.sup.3 is selected from a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, and a —CO—R.sup.4 wherein R.sup.4 is selected from a hydrogen and a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; an aryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; and d) a branched C.sub.3-6 alkyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, C.sub.1-6 alkyl, and methylsulphonyl; a heterocycle, such as a heteroaryl or heterocycloalkyl, optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a —SO.sub.2—NHR.sup.3 wherein R.sup.3 is selected from a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, and a —CO—R.sup.4 wherein R.sup.4 is selected from a hydrogen and a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; an aryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl.

28. The compound of claim 19, wherein R.sup.1 is selected from the group consisting of a) a phosphate, b) a sulphate, c) a C.sub.1-3 alkyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, C.sub.1-3 alkyl, and methylsulphonyl; a heteroaryl, optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl; a —SO.sub.2—NHR.sup.3 wherein R.sup.3 is selected from a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl, and a —CO—R.sup.4 wherein R.sup.4 is selected from a hydrogen and a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl; an aryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl; and d) a branched C.sub.3-6 alkyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, C.sub.1-3 alkyl, and methylsulphonyl; a heteroaryl, optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl; a —SO.sub.2—NHR.sup.3 wherein R.sup.3 is selected from a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl, and a —CO—R.sup.4 wherein R.sup.4 is selected from a hydrogen and a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl; an aryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl.

29. The compound of claim 19, wherein R.sup.1 is selected from the group consisting of a phosphate, a sulphate and a methyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is methylsulphonyl; oxazolyl; tetrazolyl; a phenyl substituted with at least one from the group consisting of a halogen and hydroxy, such as R.sup.1 is selected from the group consisting of a phosphate, a sulphate and a methyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —CONHR.sup.2 wherein R.sup.2 is methylsulphonyl; oxazolyl; tetrazolyl; a phenyl substituted with at least one from the group consisting of a halogen and hydroxy.

30. The compound of claim 19, selected from the group consisting of 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-phospho-1-thio-α-D-galactopyranoside, 3,4-Dichlorphenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-phospho-1-thio-α-D-galactopyranoside, 3,4-Dichlorphenyl 3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-sulfo-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-sulfo-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(phosphonooxy)methyl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorphenyl 2-O-carboxymethyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorphenyl 2-O-carboxymethyl-3-deoxy-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 2-O-Carboxymethyl-3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorphenyl 3-Deoxy-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[2-(methylsulfonamido)-2-oxoethyl]-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-(oxazol-4-ylmethyl)-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 3-Deoxy-3-[4-(3,4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorphenyl 3-Deoxy-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorphenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-imidazol-2-yl)methyl]-1-thio-α-D- galactopyranoside, 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1-methyl-1H-imidazol-2-yl)methyl]-1-thio-α- D-galactopyranoside, 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(oxazol-2-yl)methyl]-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(oxazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(isoxazol-3-yl)methyl]-1-thio-α-D-galactopyranoside, 3,4-Dichlorphenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-[(oxazol-4-yl)methyl]-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-4-yl)methyl]-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-2-yl)methyl]-1-thio-α-D-galactopyranoside, 4-Chloro-N,N-dimethyl-benzamide-2-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-4-yl)methyl]-1-thio-α-D-galactopyranoside, 4-Chloro-N,N-dimethyl-benzamide-2-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 2-O-carboxypropyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, 5-Bromopyridin-3-yl 2-O-(1-carboxy)ethyl)-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (Diastereomer 1), and 5-Bromopyridin-3-yl 2-O-(1-carboxy)ethyl)-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (Diastereomer 2); or a pharmaceutically acceptable salt or solvate thereof.

31. The compound of claim 19 for use as a medicine.

32. A pharmaceutical composition comprising the compound of claim 19 and optionally a pharmaceutically acceptable additive.

33. A method for treatment of a disorder relating to the binding of a galectin-3 to a ligand in a mammal, wherein a therapeutically effective amount of at least one compound according to claim 1 is administered to a mammal in need of said treatment; wherein said disorder is selected from the group consisting of inflammation; fibrosis, such as pulmonary fibrosis, liver fibrosis, kidney fibrosis, ophthalmological fibrosis and fibrosis of the skin and heart; scarring; keloid formation; aberrant scar formation; surgical adhesions; septic shock; cancer, such as carcinomas, sarcomas, leukemias and lymphomas, such as T-cell lymphomas; metastasising cancers; autoimmune diseases, such as psoriasis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; metabolic disorders; heart disease; heart failure; pathological angiogenesis, such as ocular angiogenesis or a disease or condition associated with ocular angiogenesis, e.g. neovascularization related to cancer; and eye diseases, such as age-related macular degeneration and corneal neovascularization; atherosclerosis; metabolic diseases such as diabetes; type 2 diabetes; insulin resistens; obesity; Diastolic HF; asthma and other interstitial lung diseases, including Hermansky-Pudlak syndrome, mesothelioma; liver disorders, such as non-alcoholic steatohepatitis.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0129] The compounds of the present invention are novel galactopyranose compounds that unexpectedly have good solubility and can be used to increase the maximum dose resulting in dose correlated bioavailability. The compounds of the present invention have high affinity to galectin 3 and inhibits galectin 3. As further shown the compounds of the present invention have high selectivity towards galectin 3 over galectin 1. Here compounds have been developed in which one modifying group is introduced at the C2 oxygen of a galactopyranose.

[0130] Preferably, the pyranose ring is α-D-galactopyranose which compounds have very good solubility and suitability as galectin 3 inhibitors. In particular, the galactopyranose ring with a C.sub.2 modification have aqueous solubility above 1.5 mg/ml, and in some instances above 10 mg/ml.

[0131] In broad aspect the present invention concerns a compound of formula (I)

##STR00019##

wherein the pyranose ring is α- or β-D-galactopyranose (as indicated by wavy line); and wherein R.sup.1, A.sup.1, X.sup.1 and B.sup.1 are as defined above.

[0132] In one embodiment A.sup.1 is selected from a heteroaryl substituted with at least one from the group consisting of a halogen; CN; C.sub.2-6 alkenyl; C.sub.2-6 alkynyl; carboxyl; C.sub.1-6 alkoxy; C.sub.1-6 thioalkyl; an amino; an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; an aryl; an aryl substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a heteroaryl; a heteroaryl substituted with at least one from the group consisting of halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkoxy, and C.sub.3-7 cycloalkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a C.sub.1-6 carbonyl; a C.sub.1-6 carbonyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl. In a more specific embodiment A.sup.1 is a heteroaryl substituted with an aryl substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl. In a still more specific embodiment A.sup.1 is a triazolyl, such as a 1,2,3-triazolyl, substituted with a phenyl substituted with at least one halogen, such a 1, 2 or 3 F, or 2F and one Cl.

[0133] In another embodiment X.sup.1 is selected from the group consisting of O and S. Preferably X.sup.1 is S.

[0134] In a further embodiment B.sup.1 is selected from the group consisting of d) an aryl substituted with at least one from the group consisting of halogen; cyano; hydroxy; carboxyl; carboxamid; carboxamid substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.3-6 cycloalkyl; C.sub.1-6 alkyl; C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.&—CONH— wherein R.sup.& is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.%-CONH— wherein R.sup.% is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 alkoxy; C.sub.1-6 alkoxy substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.§ —CONH— wherein R.sup.§ is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.3-6 cycloalkoxy; C.sub.3-6 cycloalkoxy substituted with at least one from the group consisting of halogen, hydroxy, and R*—CONH— wherein R* is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; amino; amino substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; and R**—CONH— wherein R** is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; and g) a heteroaryl substituted with at least one from the group consisting of halogen; cyano; hydroxy; carboxyl; carboxamid; carboxamid substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.3-6 cycloalkyl; C.sub.1-6 alkyl; C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.&&—CONH— wherein R.sup.&& is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.%%—CONH— wherein R.sup.%% is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 alkoxy; C.sub.1-6 alkoxy substituted with at least one from the group consisting of halogen, hydroxy, and R″—CONH— wherein R″ is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.3-6 cycloalkoxy; C.sub.3-6 cycloalkoxy substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.a—CONH— wherein W; is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; amino; amino substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; R.sup.aa—CONH— wherein R.sup.aa is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; a heteroaryl substituted with at least one from the group consisting of a halogen; an amino; an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; an aryl; an aryl substituted with at least one from the group consisting of a halogen, cyano, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a heteroaryl; a heteroaryl substituted with at least one from the group consisting of halogen, cyano, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkoxy, and C.sub.3-7 cycloalkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a C.sub.1-6 carbonyl; and a C.sub.1-6 carbonyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl. Preferably B.sup.1 is selected from the group consisting of d) a phenyl substituted with at least one from the group consisting of halogen; cyano; hydroxy; carboxyl; carboxamid; carboxamid substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.3-6 cycloalkyl; C.sub.1-6 alkyl; C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.&—CONH— wherein R.sup.& is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl substituted with at least one from the group consisting of halogen, hydroxy, and R %—CONH— wherein R % is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 alkoxy; C.sub.1-6 alkoxy substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.§ —CONH— wherein R.sup.§ is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.3-6 cycloalkoxy; C.sub.3-6 cycloalkoxy substituted with at least one from the group consisting of halogen, hydroxy, and R*—CONH— wherein R* is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; amino; amino substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; and R**—CONH— wherein R** is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; and g) a pyridinyl substituted with at least one from the group consisting of halogen; cyano; hydroxy; carboxyl; carboxamid; carboxamid substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.3-6 cycloalkyl; C.sub.1-6 alkyl; C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.&&—CONH— wherein R.sup.&& is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl; C.sub.1-6 cycloalkyl substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.%%—CONH— wherein R.sup.%% is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.1-6 alkoxy; C.sub.1-6 alkoxy substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.§§ —CONH— wherein R.sup.§§ is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; C.sub.3-6 cycloalkoxy; C.sub.3-6 cycloalkoxy substituted with at least one from the group consisting of halogen, hydroxy, and R.sup.a—CONH— wherein W; is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; amino; amino substituted with at least one from the group consisting of C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; R.sup.aa—CONH— wherein R.sup.aa is selected from the group consisting C.sub.1-6 alkyl and C.sub.1-6 cycloalkyl; a heteroaryl substituted with at least one from the group consisting of a halogen; an amino; an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; an aryl; an aryl substituted with at least one from the group consisting of a halogen, cyano, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a heteroaryl; a heteroaryl substituted with at least one from the group consisting of halogen, cyano, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, C.sub.3-7 cycloalkoxy, and C.sub.3-7 cycloalkoxy substituted with at least one from the group consisting of a halogen, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a C.sub.1-6 carbonyl; and a C.sub.1-6 carbonyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.1-6 alkyl substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, nitro, thio, C.sub.1-6 alkylthio, amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl. Most preferably B.sup.1 is selected from the group consisting of d) a phenyl substituted with at least one halogen, such as 1 or 2 Cl; and g) a pyridinyl substituted with at least one halogen, such as 1 Br.

[0135] In a further embodiment of the compound of formula I or II of the present invention R.sup.1 is selected from the group consisting of a) a phosphate, b) a sulphate, c) a C.sub.1-6 alkyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, C.sub.1-6 alkyl, and methylsulphonyl; a heterocycle, such as a heteroaryl or heterocycloalkyl, optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a —SO.sub.2—NHR.sup.3 wherein R.sup.3 is selected from a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, and a —CO—R.sup.4 wherein R.sup.4 is selected from a hydrogen and a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; an aryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; and d) a branched C.sub.3-6 alkyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, C.sub.1-6 alkyl, and methylsulphonyl; a heterocycle, such as a heteroaryl or heterocycloalkyl, optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a —SO.sub.2—NHR.sup.3 wherein R.sup.3 is selected from a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl, and a —CO—R.sup.4 wherein R.sup.4 is selected from a hydrogen and a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; an aryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl.

[0136] In a still further embodiment of the compound of formula I or II of the present invention R.sup.1 is selected from R.sup.1 is selected from the group consisting of a) a phosphate, b) a sulphate, c) a C.sub.1-3 alkyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, C.sub.1-3 alkyl, and methylsulphonyl; a heteroaryl, optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl; a —SO.sub.2—NHR.sup.3 wherein R.sup.3 is selected from a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl, and a —CO—R.sup.4 wherein R.sup.4 is selected from a hydrogen and a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl; an aryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl; and d) a branched C.sub.3-6 alkyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, C.sub.1-3 alkyl, and methylsulphonyl; a heteroaryl, optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl; a —SO.sub.2—NHR.sup.3 wherein R.sup.3 is selected from a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl, and a —CO—R.sup.4 wherein R.sup.4 is selected from a hydrogen and a heterocycle optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl; an aryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-3 alkoxy, C.sub.1-3 thioalkyl, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy, C.sub.1-3 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-3 alkoxy, C.sub.1-3 alkyl, nitro, thio, C.sub.1-3 alkylthio, amino, hydroxy and C.sub.1-3 carbonyl.

[0137] In a further embodiment R.sup.1 is selected from the group consisting of a phosphate, a sulphate and a C.sub.1-4 alkyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, C.sub.1-4 alkyl, and methylsulphonyl; a heteroaryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-4 alkoxy, C.sub.1-4 thioalkyl, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy, C.sub.1-4 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy and C.sub.1-4 carbonyl; an aryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-4 alkoxy, C.sub.1-4 thioalkyl, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy, C.sub.1-4 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy and C.sub.1-4 carbonyl. Each of these R.sup.1 groups can be made subject of individual embodiments in connection with any one of the above embodiments and aspects of the present invention

[0138] In a still further embodiment R.sup.1 is selected from the group consisting of a phosphate, a sulphate and a C.sub.1-3 alkyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, C.sub.1-3 alkyl, and methylsulphonyl; a heteroaryl selected from the group consisting of oxazolyl, imidazolyl, isoxazolyl and tetrazolyl, such as oxazolyl and tetrazolyl, optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl; a phenyl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, carboxyl, C.sub.1-6 alkoxy, C.sub.1-6 thioalkyl, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy, C.sub.1-6 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkyl, nitro, thio, C.sub.1-6 alkylthio, amino, hydroxy and C.sub.1-6 carbonyl. Each of these R.sup.1 groups can be made subject of individual embodiments in connection with any one of the above embodiments and aspects of the present invention

[0139] In a further embodiment R.sup.1 is selected from the group consisting of a phosphate, a sulphate and a C.sub.1-3 alkyl substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, C.sub.1-3 alkyl, and methylsulphonyl; a heteroaryl selected from the group consisting of oxazolyl, imidazolyl, isoxazolyl and tetrazolyl, such as oxazolyl and tetrazolyl, optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-4 alkoxy, C.sub.1-4 thioalkyl, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy, C.sub.1-4 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy and C.sub.1-4 carbonyl; an aryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-4 alkoxy, C.sub.1-4 thioalkyl, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy, C.sub.1-4 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy and C.sub.1-4 carbonyl. Each of these R.sup.1 groups can be made subject of individual embodiments in connection with any one of the above embodiments and aspects of the present invention

[0140] In a still further embodiment R.sup.1 is selected from the group consisting of a phosphate, a sulphate and a C.sub.1-3 alkyl, such as methyl, substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, methyl, and methylsulphonyl; a heteroaryl selected from the group consisting of oxazolyl, imidazolyl, isoxazolyl and tetrazolyl, such as oxazolyl and tetrazolyl, optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-4 alkoxy, C.sub.1-4 thioalkyl, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy, C.sub.1-4 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy and C.sub.1-4 carbonyl; an aryl optionally substituted with at least one from the group consisting of a halogen, CN, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, carboxyl, C.sub.1-4 alkoxy, C.sub.1-4 thioalkyl, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy, C.sub.1-4 carbonyl, an amino, and an amino substituted with at least one from the group consisting of halogen, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, nitro, thio, C.sub.1-4 alkylthio, amino, hydroxy and C.sub.1-4 carbonyl. Each of these R.sup.1 groups can be made subject of individual embodiments in connection with any one of the above embodiments and aspects of the present invention

[0141] In a further embodiment R.sup.1 is selected from the group consisting of a phosphate, a sulphate and a C.sub.1-3 alkyl, such as methyl, substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is selected from hydrogen, methyl, and methylsulphonyl; imidazolyl optionally substituted with a methyl; isoxazolyl; oxazolyl; tetrazolyl; a phenyl substituted with at least one from the group consisting of a halogen and hydroxy. Each of these R.sup.1 groups can be made subject of individual embodiments in connection with any one of the above embodiments and aspects of the present invention

[0142] In a still further embodiment R.sup.1 is selected from the group consisting of a phosphate, a sulphate and a C.sub.1-3 alkyl, such as methyl, substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is methylsulphonyl; isoxazolyl; imidazolyl optionally substituted with a methyl; oxazolyl; tetrazolyl; a phenyl substituted with at least one from the group consisting of a halogen, such as F, and hydroxy. Each of these R.sup.1 groups can be made subject of individual embodiments in connection with any one of the above embodiments and aspects of the present invention.

[0143] In a further embodiment R.sup.1 is selected from the group consisting of a phosphate, a sulphate and a C.sub.1-3 alkyl, such as methyl, substituted with a group selected from a phosphate, an oxy phosphonyl, a —COOH, a —CONHR.sup.2 wherein R.sup.2 is methylsulphonyl; oxazolyl; tetrazolyl; a phenyl substituted with at least one from the group consisting of a halogen, such as F, and hydroxy. Each of these R.sup.1 groups can be made subject of individual embodiments in connection with any one of the above embodiments and aspects of the present invention.

[0144] In a further embodiment of the present invention the compound is selected from a compound of formula II

##STR00020##

wherein the pyranose ring is α-D-galactopyranose,
wherein

[0145] A.sup.2 is selected from A.sup.1 as defined above;

[0146] X.sup.1 is selected from S, SO, SO.sub.2, O, C═O, and CR.sup.32aR.sup.33a wherein R.sup.32a and R.sup.33a are independently selected from hydrogen, OH, or halogen;

[0147] B.sup.2 is selected from B.sup.1 as defined above;

[0148] R.sup.1 is as defined above; or

[0149] a pharmaceutically acceptable salt or solvate thereof.

[0150] In a further embodiment A.sup.2 is selected from

##STR00021##

[0151] wherein Het.sup.1a is selected from a five or six membered heteroaromatic ring, optionally substituted with a group selected from Br; F; Cl; CN; NR.sup.19aR.sup.20a, wherein R.sup.19a and R.sup.20a are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, iso-propyl, —C(═O)—R.sup.21a, wherein R.sup.21a is selected from H and C.sub.1-3 alkyl; C.sub.1-3 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; and OC.sub.1-3 alkyl optionally substituted with a F;

[0152] wherein R.sup.1a—R.sup.5a are independently selected from H, CN, NH.sub.2, Cl, F, methyl optionally substituted with a F, and OCH.sub.3 optionally substituted with a F;

[0153] wherein R.sup.6a is selected from C.sub.1-6 alkyl optionally substituted with a halogen, branched C.sub.3-6 alkyl and C.sub.3-7 cycloalkyl;

[0154] wherein R.sup.7a 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 OCH.sub.3 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 OCH.sub.3 optionally substituted with a F;

[0155] wherein R.sup.8a—R.sup.12a are independently selected from H, F, methyl optionally substituted with a F, and OCH.sub.3 optionally substituted with a F;

[0156] wherein R.sup.13a 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 OCH.sub.3 optionally substituted with a F, or an aryl, such as phenyl or naphthyl, optionally substituted with a group selected from H, OH, F, methyl optionally substituted with a F, and OCH.sub.3 optionally substituted with a F. Preferably, A.sup.2 is formula 2a, wherein R.sup.1a—R.sup.5a are independently selected from H, Cl, CN, NH.sub.2, F, methyl optionally substituted with a F, and OCH.sub.3 optionally substituted with a F. More preferred A.sup.2 is formula 2a, wherein R.sup.1a and R.sup.5a are hydrogen, and R.sup.2a—R.sup.4a are independently selected from H, Cl, CN, NH.sub.2, F, methyl optionally substituted with a F, and OCH.sub.3 optionally substituted with a F. Most preferred A.sup.2 is formula 2a, wherein R.sup.1a and R.sup.5a are hydrogen, and R.sup.2a—R.sup.4a are independently selected from hydrogen, Cl and F. Typically, A.sup.2 is formula 2a, wherein R.sup.1a and R.sup.5a are hydrogen, and R.sup.2a—R.sup.4a are all F or R.sup.2a—R.sup.4a are selected from Cl and F. Typically, A.sup.2 is formula 2a, wherein R.sup.1a and R.sup.5a are hydrogen, and R.sup.2a—R.sup.4a are selected from Cl and F, wherein one is Cl and the other two are F.

[0157] In a still further embodiment X.sup.1 is selected from S and O. Preferably, X.sup.1 is S. In a further embodiment B.sup.2 is selected from a) a C.sub.1-6 alkyl or branched C.sub.3-6 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, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.14a—CONH— wherein R.sup.14a is selected from C.sub.1-3 alkyl and cyclopropyl; or a C.sub.1-6 alkyl substituted with a phenyl, optionally substituted with a substituent selected from CN, a halogen, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.15a—CONH— wherein R.sup.15a is selected from C.sub.1-3 alkyl and cyclopropyl; b) an aryl, such as phenyl or naphthyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.22aR.sup.23a, wherein R.sup.22a and R.sup.23a are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.28aR.sup.29a, wherein R.sup.28a and R.sup.29a are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.16a—CONH— wherein R.sup.16a is selected from C.sub.1-3 alkyl and cyclopropyl; c) a C.sub.5-7 cycloalkyl, optionally substituted with a substituent selected from a halogen, CN, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.17a—CONH— wherein R.sup.17a is selected from C.sub.1-3 alkyl and cyclopropyl; and d) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.24aR.sup.25a, wherein R.sup.24a and R.sup.25a are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.30aR.sup.31a, wherein R.sup.30a and R.sup.31a are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.18a—CONH— wherein R.sup.18a is selected from C.sub.1-3 alkyl and cyclopropyl; e) a C.sub.1-6 alkyl or branched C.sub.3-6 alkyl.

[0158] In a still further embodiment B.sup.2 is selected from b) an aryl, such as phenyl or naphthyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.22aR.sup.23a, wherein R.sup.22a and R.sup.23a are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.28aR.sup.29a, wherein R.sup.28a and R.sup.29a are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.16a—CONH— wherein R.sup.16a is selected from C.sub.1-3 alkyl and cyclopropyl; and d) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.24aR.sup.25a, wherein R.sup.24a and R.sup.25a are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.30aR.sup.31a, wherein R.sup.30a and R.sup.31a are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.18a—CONH— wherein R.sup.18a is selected from C.sub.1-3 alkyl and cyclopropyl. In a further embodiment B.sup.2 is selected from b) a phenyl optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.22aR.sup.23a, wherein R.sup.22a and R.sup.23a are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.28aR.sup.29a, wherein R.sup.28a and R.sup.29a are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.16a—CONH— wherein R.sup.16a is selected from C.sub.1-3 alkyl and cyclopropyl; and d) a heteroaryl optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.24aR.sup.25a, wherein R.sup.ea and R.sup.25a are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.30aR.sup.31a, wherein R.sup.30a and R.sup.31a are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.18a—CONH— wherein R.sup.18a is selected from C.sub.1-3 alkyl and cyclopropyl. In a still further embodiment B.sup.2 is selected from b) a phenyl substituted with a halogen, such as Cl. In a further embodiment B.sup.2 is selected from b) a phenyl substituted with a halogen, such as Cl, and a —CONR.sup.22aR.sup.23a, wherein R.sup.22a and R.sup.23a are independently selected from H, C.sub.1-3 alkyl. In another embodiment B.sup.2 is selected form d) a heteroaryl, such as a pyridinyl, substituted with a halogen.

[0159] In a further embodiment R.sup.1 is any one of the above defined embodiments.

[0160] In a further embodiment of the present invention the compound is selected from a compound of formula II

##STR00022##

wherein the pyranose ring is α-D-galactopyranose,

[0161] A2 is

##STR00023##

wherein Het.sup.1c is a five or six membered heteroaromatic ring selected from the group consisting of formulas 2c to 9c:

##STR00024##

wherein R.sup.2c to R.sup.23c and R.sup.27c are independently selected from H; halogen; OH; CN; SH; S—C.sub.1-3 alkyl; C.sub.1-3 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; OC.sub.1-3 alkyl optionally substituted with a F; NR.sup.24cR.sup.25c, wherein R.sup.24c is selected from H, and C.sub.1-3 alkyl, and R.sup.25c is selected from H, C.sub.1-3 alkyl, and COR.sup.26c, wherein R.sup.26c is selected from H, and C.sub.1-3 alkyl;

[0162] X.sup.1 is selected from S;

[0163] B.sup.2 is selected from a) a C.sub.1-6 alkyl or branched C.sub.3-6 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, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.27#—CONH— wherein R.sup.27# is selected from C.sub.1-3 alkyl and cyclopropyl; or a C.sub.1-6 alkyl substituted with a phenyl, optionally substituted with a substituent selected from CN, a halogen, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.28c—CONH— wherein R.sup.28c is selected from C.sub.1-3 alkyl and cyclopropyl; b) a phenyl optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.29cR.sup.30c, wherein R.sup.29c and R.sup.30c are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.31cR.sup.32c, wherein R.sup.31c and R.sup.32c are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.33c—CONH—, wherein R.sup.33c is selected from C.sub.1-3 alkyl and cyclopropyl; c) a C.sub.5-7 cycloalkyl, optionally substituted with a substituent selected from a halogen, CN, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, OCH.sub.2CH.sub.3 optionally substituted with a F, OH, and R.sup.34c—CONH— wherein R.sup.34c is selected from C.sub.1-3 alkyl and cyclopropyl; and d) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.35cR.sup.36c, wherein R.sup.35c and R.sup.36c are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.37cR.sup.38c, wherein R.sup.37c and R.sup.38c are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.39c—CONH— wherein R.sup.30c is selected from C.sub.1-3 alkyl and cyclopropyl; e) a C.sub.1-6 alkyl or branched C.sub.3-6 alkyl; R.sup.1 is an acid isostere having one or two lone pairs or an acidic proton, or both; or

[0164] a pharmaceutically acceptable salt or solvate thereof.

[0165] In a still further embodiment of the present invention the compound is selected from a compound of formula II

##STR00025##

wherein the pyranose ring is α-D-galactopyranose,

[0166] A.sup.2 is

##STR00026##

[0167] wherein Het.sup.1d is selected from the group consisting of

##STR00027##

[0168] wherein R.sup.2d is selected from the group consisting of OH and halogen;

[0169] R.sup.3d is selected from the group consisting of hydrogen, C.sub.1-6 alkyl and halogen;

[0170] R.sup.4d is selected from the group consisting of OH and halogen;

[0171] R.sup.5d is selected from the group consisting of hydrogen, C.sub.1-6 alkyl and halogen;

[0172] X.sup.1 is S;

[0173] B.sup.2 is selected from a) an aryl, such as phenyl or naphthyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.29dR.sup.30d, wherein R.sup.29d and R.sup.30d are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; SC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.31dR.sup.32d, wherein R.sup.31d and R.sup.32d are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.33d—CONH—, wherein R.sup.33d is selected from C.sub.1-3 alkyl and cyclopropyl; b) a heterocycle, such as heteroaryl or heterocycloalkyl, optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.35dR.sup.36d, wherein R.sup.35d and R.sup.36d are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; SC.sub.1-3 alkyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.37dR.sup.38d, wherein R.sup.37d and R.sup.38d are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.39d—CONH— wherein R.sup.3911 is selected from C.sub.1-3 alkyl and cyclopropyl;

R.sup.1 is an acid isostere having one or two lone pairs or an acidic proton, or both; or

[0174] a pharmaceutically acceptable salt or solvate thereof.

[0175] In a further embodiment of the present invention the compound is selected from a compound of formula II

##STR00028##

wherein the pyranose ring is α-D-galactopyranose,
wherein

[0176] A.sup.2 is selected from A.sup.1 as defined above;

[0177] X.sup.1 is selected from S, SO, SO.sub.2, and O;

[0178] B.sup.2 is selected from B.sup.1 as defined above;

[0179] R.sup.1 is as defined above; or

[0180] a pharmaceutically acceptable salt or solvate thereof.

[0181] In an embodiment A.sup.2 is selected from

##STR00029##

[0182] wherein Het.sup.1b is selected from a pyridinyl, optionally substituted with a group selected from H, CN, Br, Cl, I, F, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, and SCH.sub.3 optionally substituted with a F; or a pyrimidyl, optionally substituted with a group selected from H, CN, Br, Cl, I, F, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, and SCH.sub.3 optionally substituted with a F.

[0183] In another embodiment A.sup.2 is selected from

##STR00030##

[0184] wherein R.sup.1b—R.sup.5b are independently selected from a group consisting of H, CN, Br, Cl, I, F, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, and SCH.sub.3 optionally substituted with a F. Preferably, A.sup.2 is formula 2b, and R.sup.1b and R.sup.5b are both hydrogen, and R.sup.2b—R.sup.4b are independently selected from a group consisting of H, CN, Br, Cl, I, F, methyl optionally substituted with a F, OCH.sub.3 optionally substituted with a F, and SCH.sub.3 optionally substituted with a F. Typically, A.sup.2 is formula 2b, and R.sup.1b and R.sup.5b are both hydrogen, and R.sup.2b—R.sup.4b are independently selected from a group consisting of H, Br, Cl, I, and F, for instance R.sup.2b—R.sup.4b are all F or R.sup.2b—R.sup.4b are selected from F and Cl, e.g. R.sup.2b is F, R.sup.3b is Cl and R.sup.4b is F.

[0185] In a further embodiment X.sup.1 is S.

[0186] In a still further embodiment B.sup.2 is selected from b) a phenyl optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.22bR.sup.23b, wherein R.sup.22b and R.sup.23b are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.28bR.sup.29b, wherein R.sup.28b and R.sup.29b are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.16b—CONH— wherein R.sup.16b is selected from C.sub.1-3 alkyl and cyclopropyl; and d) a heteroaryl optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.24bR.sup.25b, wherein R.sup.24b and R.sup.25b are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.30bR.sup.31b, wherein R.sup.30b and R.sup.31b are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.18b—CONH— wherein R.sup.18b is selected from C.sub.1-3 alkyl and cyclopropyl.

[0187] In one embodiment B.sup.2 is selected from a phenyl optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.22bR.sup.23b, wherein R.sup.22b and R.sup.23b are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.28bR.sup.29b, wherein R.sup.28b and R.sup.29b are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.16b—CONH— wherein R.sup.16b is selected from C.sub.1-3 alkyl and cyclopropyl. Typically, B.sup.2 is selected from a phenyl substituted with a halogen, such as 1-3 selected from Cl, F, Br, and I. In a particular embodiment B.sup.2 is selected from a phenyl substituted with 1-3 Cl, such as two Cl.

[0188] In another embodiment B.sup.2 is selected from a heteroaryl optionally substituted with a group selected from a halogen; CN; —COOH; —CONR.sup.24bR.sup.25b, wherein R.sup.24b and R.sup.25b are independently selected from H, C.sub.1-3 alkyl, cyclopropyl, and iso-propyl; C.sub.1-3 alkyl, optionally substituted with a F; cyclopropyl, optionally substituted with a F; isopropyl, optionally substituted with a F; OC.sub.1-3 alkyl, optionally substituted with a F; O-cyclopropyl, optionally substituted with a F; O-isopropyl, optionally substituted with a F; NR.sup.30bR.sup.31b, wherein R.sup.30b and R.sup.31b are independently selected from H, C.sub.1-3 alkyl and isopropyl; OH; and R.sup.18b—CONH— wherein R.sup.18b is selected from C.sub.1-3 alkyl and cyclopropyl. Typically, B.sup.2 is selected from a pyridinyl substituted with a halogen, such as 1-3 selected from Cl, F, Br, and I. In a particular embodiment B.sup.2 is selected from a pyridinyl substituted with 1-3 Br, such as one Br.

[0189] In a still further embodiment of the present invention wherein the compound has formula II, wherein A.sup.2 is formula 2b, X.sup.1 is selected from S, SO, SO.sub.2, and O; and B.sup.2 is selected from B.sup.1 as defined above, R.sup.1 is selected from any one of the above defined embodiments.

[0190] In a further embodiment of the present invention the compound of formula I or II is selected from [0191] 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-phospho-1-thio-α-D-galactopyranoside, [0192] 3,4-Dichlorphenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-phospho-1-thio-α-D-galactopyranoside, [0193] 3,4-Dichlorphenyl 3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-sulfo-1-thio-α-D-galactopyranoside, [0194] 5-Bromopyridin-3-yl 3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-sulfo-1-thio-α-D-galactopyranoside, [0195] 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(phosphonooxy)methyl]-1-thio-α-D-galactopyranoside, [0196] 3,4-Dichlorphenyl 2-O-carboxymethyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, [0197] 3,4-Dichlorphenyl 2-O-carboxymethyl-3-deoxy-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, [0198] 5-Bromopyridin-3-yl 2-O-Carboxymethyl-3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, [0199] 3,4-Dichlorphenyl 3-Deoxy-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[2-(methylsulfonamido)-2-oxoethyl]-1-thio-α-D-galactopyranoside, [0200] 5-Bromopyridin-3-yl 3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-(oxazol-4-ylmethyl)-1-thio-α-D-galactopyranoside, [0201] 5-Bromopyridin-3-yl 3-Deoxy-3-[4-(3,4,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside, [0202] 5-Bromopyridin-3-yl 3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, [0203] 3,4-Dichlorphenyl 3-Deoxy-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, [0204] 3,4-Dichlorphenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, [0205] 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-imidazol-2-yl)methyl]-1-thio-α-D-galactopyranoside, [0206] 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1-methyl-1H-imidazol-2-yl)methyl]-1-thio-α-D-galactopyranoside, [0207] 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(oxazol-2-yl)methyl]-1-thio-α-D-galactopyranoside, [0208] 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(oxazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, [0209] 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(isoxazol-3-yl)methyl]-1-thio-α-D-galactopyranoside, [0210] 3,4-Dichlorphenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-[(oxazol-4-yl)methyl]-1-thio-α-D-galactopyranoside, [0211] 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-4-yl)methyl]-1-thio-α-D-galactopyranoside, [0212] 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, [0213] 5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-2-yl)methyl]-1-thio-α-D-galactopyranoside, [0214] 4-Chloro-N,N-dimethyl-benzamide-2-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-4-yl)methyl]-1-thio-α-D-galactopyranoside, [0215] 4-Chloro-N,N-dimethyl-benzamide-2-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside, [0216] 5-Bromopyridin-3-yl 2-O-carboxypropyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside, [0217] 5-Bromopyridin-3-yl 2-O-(1-carboxy)ethyl)-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (Diastereomer 1), and [0218] 5-Bromopyridin-3-yl 2-O-(1-carboxy)ethyl)-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (Diastereomer 2).

[0219] In a further aspect the present invention relates to a compound of the present invention for use as a medicine. In one embodiment the compound has formula I. In a more preferred embodiment the compound has formula II.

[0220] In a still further aspect the present invention relates to a pharmaceutical composition comprising a compound of formula I or II of the present invention and optionally a pharmaceutically acceptable additive, such as a carrier and/or excipient.

[0221] In a further aspect the present invention relates to a compound of formula I or II of the present invention for use in a method for treating a disorder relating to the binding of a galectin-3 to a ligand in a mammal, such as a human. In an embodiment the disorder is selected from the group consisting of inflammation; fibrosis, such as pulmonary fibrosis, liver fibrosis, kidney fibrosis, ophthalmological fibrosis and fibrosis of the skin and heart; scarring; keloid formation; aberrant scar formation; surgical adhesions; septic shock; cancer, such as carcinomas, sarcomas, leukemias and lymphomas, such as T-cell lymphomas; metastasising cancers; autoimmune diseases, such as psoriasis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; metabolic disorders; heart disease; heart failure; pathological angiogenesis, such as ocular angiogenesis or a disease or condition associated with ocular angiogenesis, e.g. neovascularization related to cancer; and eye diseases, such as age-related macular degeneration and corneal neovascularization; atherosclerosis; metabolic diseases such as diabetes; type 2 diabetes; insulin resistens; obesity; Diastolic HF; asthma and other interstitial lung diseases, including Hermansky-Pudlak syndrome, mesothelioma; liver disorders, such as non-alcoholic steatohepatitis. A non-limiting group of cancers given as examples of cancers that may be treated, managed and/or prevented by administration of a compound of formula I or II include: colon carcinoma, breast cancer, pancreatic cancer, ovarian cancer, prostate cancer, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangeosarcoma, lymphangeoendothelia sarcoma, synovioma, mesothelioma, Ewing's sarcoma, leiomyosarcoma, rhabdomyosarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystandeocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioblastomas, neuronomas, craniopharingiomas, schwannomas, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroama, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma, leukemias and lymphomas, acute lymphocytic leukemia and acute myelocytic polycythemia vera, multiple myeloma, Waldenstrom's macroglobulinemia, and heavy chain disease, acute nonlymphocytic leukemias, chronic lymphocytic leukemia, chronic myelogenous leukemia, Hodgkin's Disease, non-Hodgkin's lymphomas, rectum cancer, urinary cancers, uterine cancers, oral cancers, skin cancers, stomach cancer, brain tumors, liver cancer, laryngeal cancer, esophageal cancer, mammary tumors, childhood-null acute lymphoid leukemia (ALL), thymic ALL, B-cell ALL, acute myeloid leukemia, myelomonocytoid leukemia, acute megakaryocytoid leukemia, Burkitt's lymphoma, acute myeloid leukemia, chronic myeloid leukemia, and T cell leukemia, small and large non-small cell lung carcinoma, acute granulocytic leukemia, germ cell tumors, endometrial cancer, gastric cancer, cancer of the head and neck, chronic lymphoid leukemia, hairy cell leukemia and thyroid cancer. Each of these disorders is considered a single embodiment and may be made the subject of a claim specifically to such disease or disorder.

[0222] In a still further aspect the present invention relates to a method for treatment of a disorder relating to the binding of a galectin-3 to a ligand in a mammal, such as a human, wherein a therapeutically effective amount of at least one compound of formula I or II of the present invention is administered to a mammal in need of said treatment. In an embodiment the disorder is selected from the group consisting of inflammation; fibrosis, such as pulmonary fibrosis, liver fibrosis, kidney fibrosis, ophthalmological fibrosis and fibrosis of the skin and heart; scarring; keloid formation; aberrant scar formation; surgical adhesions; septic shock; cancer, such as carcinomas, sarcomas, leukemias and lymphomas, such as T-cell lymphomas; metastasising cancers; autoimmune diseases, such as psoriasis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematosus; metabolic disorders; heart disease; heart failure (HF); pathological angiogenesis, such as ocular angiogenesis or a disease or condition associated with ocular angiogenesis, e.g. neovascularization related to cancer; and eye diseases, such as age-related macular degeneration and corneal neovascularization; atherosclerosis; metabolic diseases such as diabetes; type 2 diabetes; insulin resistens; obesity; Diastolic HF; asthma and other interstitial lung diseases, including Hermansky-Pudlak syndrome, mesothelioma; liver disorders, such as non-alcoholic steatohepatitis. Each of these disorders are considered a single embodiment and may be made the subject of a claim specifically to such disease or disorder.

[0223] The skilled person will understand that it may be necessary to adjust or change the order of steps in the process a1, and such change of order is encompassed by the aspects of the process as described above in the reaction schemes and accompanying description of the process steps.

[0224] Furthermore, the skilled person will understand that the processes described above and hereinafter the functional groups of intermediate compounds may need to be protected by protecting groups.

[0225] Functional groups that it is desirable to protect include hydroxy, amino and carboxylic acid. Suitable protecting groups for hydroxy include optionally substituted and/or unsaturated alkyl groups (e.g. methyl, allyl, benzyl or tert-butyl), trialkyl silyl or diarylalkylsilyl groups (e.g. t-butyldimethylsilyl, t-butyldipheylsilyl or trimethylsilyl), AcO (acetoxy), TBS (t-butyldimethylsilyl), TMS (trimethylsilyl), PMB (p-methoxybensyl), and tetrahydropyranyl. Suitable proteting groups for carboxylic acid include (C.sub.1-6)-alkyl or benzyl esters. Suitable protecting groups for amino include t-butyloxycarbonyl, benzyloxycarbonyl, 2-(trimethylsilyl)-ethoxy-methyl or 2-trimethylsilylethoxycarbonyl (Teoc). Suitable protecting groups for S include S—C(═N)—NH.sub.2, TIPS.

[0226] The protection and deprotection of functional groups may take place before or after any reaction in the above-mentioned processes.

[0227] Furthermore the skilled person will appreciate, that, in order to obtain compounds of the invention in an alternative, and on some occasions more convenient manner, the individual process steps mentioned hereinbefore may be performed in different order, and/or the individual reactions may be performed at a different stage in the overall route (i.e. substituents may be added to and/or chemical transformations performed upon, different intermediates to those mentioned hereinbefore in conjunction with a particular reaction). This may negate, or render necessary, the need for protecting groups.

[0228] In a still further embodiment the compound of formula I or II is on free form. “On free form” as used herein means a compound of formula I or II, either an acid form or base form, or as a neutral compound, depending on the substitutents. The free form does not have any acid salt or base salt in addition. In one embodiment the free form is an anhydrate. In another embodiment the free form is a solvate, such as a hydrate.

[0229] In a further embodiment the compound of formula I or II is a crystalline form. The skilled person may carry out tests in order to find polymorphs, and such polymorphs are intended to be encompassed by the term “crystalline form” as used herein.

[0230] When the compounds and pharmaceutical compositions herein disclosed are used for the above treatment, a therapeutically effective amount of at least one compound is administered to a mammal in need of said treatment.

[0231] The term “C.sub.1-x alkyl” as used herein means an alkyl group containing 1-x carbon atoms, e.g. C.sub.1-5 or C.sub.1-6, such as methyl, ethyl, propyl, butyl, pentyl or hexyl.

[0232] The term “branched C.sub.3-6 alkyl” as used herein means a branched alkyl group containing 3-6 carbon atoms, such as isopropyl, isobutyl, tert-butyl, isopentyl, 3-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl.

[0233] The term “C.sub.3-7 cycloalkyl” as used herein means a cyclic alkyl group containing 3-7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and 1-methylcyclopropyl.

[0234] The term “C.sub.5-7 cycloalkyl” as used herein means a cyclic alkyl group containing 5-7 carbon atoms, such as cyclopentyl, cyclohexyl, or cycloheptyl.

[0235] The term “Oxo” as used herein means an oxygen atom with double bonds, also indicated as ═O.

[0236] The term “CN” as used herein means a nitril.

[0237] The term “a five or six membered heteroaromatic ring” as used herein means one five membered heteroaromatic ring or one six membered heteroaromatic ring. The five membered heteroaromatic ring contains 5 ring atoms of which one to four are heteroatoms selected from N, O, and S. The six membered heteroaromatic ring contains 6 ring atoms of which one to five are heteroatoms selected from N, O and S. Examples include thiophene, furan, pyran, pyrrole, imidazole, pyrazole, isothiazole, isooxazole, pyridine, pyrazine, pyrimidine and pyridazine. When such heteroaromatic rings are substituents they are termed thiophenyl, furanyl, pyranyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, isooxazolyl, pyridinyl, pyrazinyl, pyrimidinyl and pyridazinyl. Also included are oxazoyl, thiazoyl, thiadiazoly, oxadiazoyl, and pyridonyl.

[0238] The term “a heterocycle, such as heteroaryl or heterocycloalkyl” as used herein means a heterocycle consisting of one or more 3-7 membered ring systems containing one or more heteroatoms and wherein such ring systems may optionally be aromatic. The term “a heteroaryl” as used herein means a mono or bicyclic aromatic ringsystem containing one or more heteroatoms, such as 1-10, e.g. 1-6, selected from O, S, and N, including but not limited to oxazolyl, oxadiazolyl, thiophenyl, thiadiazolyl, thiazolyl, pyridyl, pyrimidinyl, pyridonyl, pyrimidonyl, quinolinyl, azaquionolyl, isoquinolinyl, azaisoquinolyl, quinazolinyl, azaquinazolinyl, bensozazoyl, azabensoxazoyl, bensothiazoyl, or azabensothiazoyl. The term “a heterocycloalkyl” as used herein means a mono or bicyclic 3-7 membered alifatic heterocycle containing one or more heteroatoms, such as 1-7, e.g. 1-5, selected from O, S, and N, including but not limited to piperidinyl, tetrahydropyranyl, tetrahydrothipyranyl, or piperidonyl.

[0239] The term “treatment” and “treating” as used herein means the management and care of a patient for the purpose of combating a condition, such as a disease or a disorder. The term is intended to include the full spectrum of treatments for a given condition from which the patient is suffering, such as administration of the active compound to alleviate the symptoms or complications, to delay the progression of the disease, disorder or condition, to alleviate or relief the symptoms and complications, and/or to cure or eliminate the disease, disorder or condition as well as to prevent the condition, wherein prevention is to be understood as the management and care of a patient for the purpose of combating the disease, condition, or disorder and includes the administration of the active compounds to prevent the onset of the symptoms or complications. The treatment may either be performed in an acute or in a chronic way. The patient to be treated is preferably a mammal; in particular, a human being, but it may also include animals, such as dogs, cats, cows, sheep and pigs.

[0240] The term “a therapeutically effective amount” of a compound of formula I or II of the present invention as used herein means an amount sufficient to cure, alleviate or partially arrest the clinical manifestations of a given disease and its complications. An amount adequate to accomplish this is defined as “therapeutically effective amount”. Effective amounts for each purpose will depend on the severity of the disease or injury as well as the weight and general state of the subject. It will be understood that determining an appropriate dosage may be achieved using routine experimentation, by constructing a matrix of values and testing different points in the matrix, which is all within the ordinary skills of a trained physician or veterinary.

[0241] In a still further aspect the present invention relates to a pharmaceutical composition comprising the compound of formula I or II and optionally a pharmaceutically acceptable additive, such as a carrier or an excipient.

[0242] As used herein “pharmaceutically acceptable additive” is intended without limitation to include carriers, excipients, diluents, adjuvant, colorings, aroma, preservatives etc. that the skilled person would consider using when formulating a compound of the present invention in order to make a pharmaceutical composition.

[0243] The adjuvants, diluents, excipients and/or carriers that may be used in the composition of the invention must be pharmaceutically acceptable in the sense of being compatible with the compound of formula I or II and the other ingredients of the pharmaceutical composition, and not deleterious to the recipient thereof. It is preferred that the compositions shall not contain any material that may cause an adverse reaction, such as an allergic reaction. The adjuvants, diluents, excipients and carriers that may be used in the pharmaceutical composition of the invention are well known to a person skilled within the art.

[0244] As mentioned above, the compositions and particularly pharmaceutical compositions as herein disclosed may, in addition to the compounds herein disclosed, further comprise at least one pharmaceutically acceptable adjuvant, diluent, excipient and/or carrier. In some embodiments, the pharmaceutical compositions comprise from 1 to 99 weight % of said at least one pharmaceutically acceptable adjuvant, diluent, excipient and/or carrier and from 1 to 99 weight % of a compound as herein disclosed. The combined amount of the active ingredient and of the pharmaceutically acceptable adjuvant, diluent, excipient and/or carrier may not constitute more than 100% by weight of the composition, particularly the pharmaceutical composition.

[0245] In some embodiments, only one compound as herein disclosed is used for the purposes discussed above.

[0246] In some embodiments, two or more of the compounds as herein disclosed are used in combination for the purposes discussed above.

[0247] The composition, particularly pharmaceutical composition comprising a compound set forth herein may be adapted for oral, intravenous, topical, intraperitoneal, nasal, buccal, sublingual, or subcutaneous administration, or for administration via the respiratory tract in the form of, for example, an aerosol or an air-suspended fine powder. Therefore, the pharmaceutical composition may be in the form of, for example, tablets, capsules, powders, nanoparticles, crystals, amorphous substances, solutions, transdermal patches or suppositories.

[0248] Further embodiments of the process are described in the experimental section herein, and each individual process as well as each starting material constitutes embodiments that may form part of embodiments.

[0249] The above embodiments should be seen as referring to any one of the aspects (such as ‘method for treatment’, ‘pharmaceutical composition’, ‘compound for use as a medicament’, or ‘compound for use in a method’) described herein as well as any one of the embodiments described herein unless it is specified that an embodiment relates to a certain aspect or aspects of the present invention.

[0250] All references, including publications, patent applications and patents, cited herein are hereby incorporated by reference to the same extent as if each reference was individually and specifically indicated to be incorporated by reference and was set forth in its entirety herein.

[0251] All headings and sub-headings are used herein for convenience only and should not be construed as limiting the invention in any way.

[0252] Any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

[0253] The terms “a” and “an” and “the” and similar referents as used in the context of describing the invention are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.

[0254] Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless other-wise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. Unless otherwise stated, all exact values provided herein are representative of corresponding approximate values (e.g., all exact exemplary values provided with respect to a particular factor or measurement can be considered to also pro-vide a corresponding approximate measurement, modified by “about,” where appropriate).

[0255] All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context.

[0256] The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise indicated. No language in the specification should be construed as indicating any element is essential to the practice of the invention unless as much is explicitly stated.

[0257] The citation and incorporation of patent documents herein is done for convenience only and does not reflect any view of the validity, patentability and/or enforceability of such patent documents.

[0258] The description herein of any aspect or embodiment of the invention using terms such as “comprising”, “having”, “including” or “containing” with reference to an element or elements is intended to provide support for a similar aspect or embodiment of the invention that “consists of”, “consists essentially of”, or “substantially comprises” that particular element or elements, unless otherwise stated or clearly contradicted by context (e.g., a composition described herein as comprising a particular element should be understood as also describing a composition consisting of that element, unless otherwise stated or clearly contradicted by context). This invention includes all modifications and equivalents of the subject matter recited in the aspects or claims presented herein to the maximum extent permitted by applicable law.

[0259] The present invention is further illustrated by the following examples that, however, are not to be construed as limiting the scope of protection. The features disclosed in the foregoing description and in the following examples may, both separately and in any combination thereof, be material for realizing the invention indiverse forms thereof.

Experimental Procedures (Evaluation of Kd Values)

[0260] The affinity of Example 1-28 for galectins were determined by a fluorescence anisotropy assay where the compound was used as an inhibitor of the interaction between galectin and a fluorescein tagged saccharide probe as described Sörme, P., Kahl-Knutsson, B., Huflejt, M., Nilsson, U. J., and Leffler H. (2004) Fluorescence polarization as an analytical tool to evaluate galectin-ligand interactions. Anal. Biochem. 334: 36-47, (Sörme et al., 2004) and Monovalent interactions of Galectin-1 By Salomonsson, Emma; Larumbe, Amaia; Tejler, Johan; Tullberg, Erik; Rydberg, Hanna; Sundin, Anders; Khabut, Areej; Frejd, Torbjorn; Lobsanov, Yuri D.; Rini, James M.; et al, From Biochemistry (2010), 49(44), 9518-9532, (Salomonsson et al., 2010).

TABLE-US-00001 Aqueous Solubility Galectin-1 Galectin-3 Example Name Structure (mg/mL) Kd (μM) Kd (μM) 1 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- phospho-1-thio-α-D- galactopyranoside [00031] 9.8 5.4 0.006 2 3,4-Dichlorphenyl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- phospho-1-thio-α-D- galactopyranoside [00032] nd nd 0.007 3 3,4-Dichlorphenyl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- sulfo-1-thio-α-D- galactopyranoside [00033] nd nd 0.014 4 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- sulfo-1-thio-α-D- galactopyranoside [00034] nd  3.15 0.003 5 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(phosphonooxy)methyl]- 1-thio-α-D- galactopyranoside [00035] >10    3.83 0.012 6 3,4-Dichlorphenyl 2-O- carboxymethyl-3-deoxy- 3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-1-thio- α-D-galactopyranoside [00036] nd nd 0.017 7 3,4-Dichlorphenyl 2-O- carboxymethyl-3-[4-(4- chloro-3,5- difluorophenyl)-1H- 1,2,3-triazol-1-yl]-3- deoxy-1-thio-α-D- galactopyranoside [00037] 2  2  0.0085 8 5-Bromopyridin-3-yl 2- O-carboxymethyl-3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-1-thio- α-D-galactopyranoside [00038] 1.8 1.8 0.007 9 3,4-Dichlorphenyl 3-[4- (4-chloro-3,5- difluorophenyl)-1H- 1,2,3-triazol-1-yl]-3- deoxy-2-O-[2- (methylsulfonamido)-2- oxoethyl]-1-thio-α-D- galactopyranoside [00039] 2.9 3  0.023 10 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- (oxazol-4-ylmethyl)-1- thio-α-D- galactopyranoside [00040] nd 9.2 0.024 11 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- (3,5-difluoro-4- hydroxybenzyl)-1-thio- α-D-galactopyranoside [00041] nd  0.26 0.017 12 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(1H-tetrazol-5- yl)methyl]-1-thio-α-D- galactopyranoside [00042] nd 2.4 0.016 13 3,4-Dichlorphenyl 3-[4- (4-chloro-3,5- difluorophenyl)-1H- 1,2,3-triazol-1-yl]-3- deoxy-2-O-[(1H-tetrazol- 5-yl)methyl]-1-thio-α-D- galactopyranoside [00043] nd 1.4 0.064 14 3,4-Dichlorphenyl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(1H-tetrazol-5- yl)methyl]-1-thio-α-D- galactopyranoside [00044] nd 1.8 0.008 15 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(1H-imidazol-2- yl)methyl]-1-thio-α-D- galactopyranoside [00045] nd 9.5 0.007 16 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(1-methyl-1H-imidazol- 2-yl)methyl]-1-thio-α-D- galactopyranoside [00046] nd 6.4 0.057 17 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(oxazol-2-yl)methyl]-1- thio-α-D- galactopyranoside [00047] nd 2.8 0.024 18 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(oxazol-5-yl)methyl]-1- thio-α-D- galactopyranoside [00048] nd 14.8  0.13 19 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(isoxazol-3-yl)methyl]-1- thio-α-D- galactopyranoside [00049] nd 2.9 0.032 20 3,4-Dichlorphenyl 3-[4- (4-chloro-3,5- difluorophenyl)-1H- 1,2,3-triazol-1-yl]-3- deoxy-2-O-[(oxazol-4- yl)methyl]-1-thio-α-D- galactopyranoside [00050] nd 29.7  0.087 21 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(thiazol-4-yl)methyl]-1- thio-α-D- galactopyranoside [00051] nd 8.6 0.018 22 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- (thiazol-5-yl)methyl]-1- thio-α-D- galactopyranoside [00052] nd 1.9 0.021 23 5-Bromopyridin-3-yl 3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(thiazol-2-yl)methyl]-1- thio-α-D- galactopyranoside [00053] nd 2.6 0.041 24 4-Chloro-N,N-dimethyl- benzamide-2-yl 3-deoxy- 3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(thiazol-4-yl)methyl]-1- thio-α-D- galactopyranoside [00054] nd 3.7 0.014 25 4-Chloro-N,N-dimethyl- benzamide-2-yl 3-deoxy- 3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-2-O- [(1H-tetrazol-5- yl)methyl]-1-thio-α-D- galactopyranoside [00055] nd 1.2 0.004 26 5-Bromopyridin-3-yl 2- O-carboxypropyl-3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-1-thio- α-D-galactopyranoside [00056] nd 1.5 0.010 27 5-Bromopyridin-3-yl 2- O-(1-carboxy)ethyl)-3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-1-thio- α-D-galactopyranoside (Diastereoisomer 1) [00057] nd 6.5 0.015 28 5-Bromopyridin-3-yl 2- O-(1-carboxy)ethyl)-3- deoxy-3-[4-(3,4,5- trifluorophenyl)-1H- 1,2,3-triazol-1-yl]-1-thio- α-D-galactopyranoside (Diastereoisomer 2) [00058] nd 6.4 0.006

General Experimental:

[0261] Nuclear Magnetic Resonance (NMR) spectra were recorded on a 400 MHz Bruker AVANCE III 500 instrument or a Varian instrument at 400 MHz, at 25° C.

[0262] Chemical shifts are reported in ppm (d) using the residual solvent as internal standard. Peak multiplicities are expressed as follow: s, singlet; d, doublet; dd, doublet of doublets; t, triplet; dt, doublet of triplet; q, quartet; m, multiplet; br s, broad singlet.

[0263] LC-MS were acquired on an Agilent 1200 HPLC coupled with an Agilent MSD mass spectrometer operating in ES (+) ionization mode. Column: XBridge C18 (4.6×50 mm, 3.5 μm) or SunFire C18 (4.6×50 mm, 3.5 μm). Solvent A water+0.1% TFA and solvent B Acetonitrile+0.1% TFA or solvent A water (10 mM Ammonium hydrogen carbonate) and solvent B Acetonitrile. Wavelength: 254 nM. Alternatively LC-MS were acquired on an Agilent 1100 HPLC coupled with an Agilent MSD mass spectrometer operating in ES (+) ionization mode. Column: Waters symmetry 2.1×30 mm C18 or Chromolith RP-18 2×50 mm Solvent A water+0.1% TFA and solvent B Acetonitrile+0.1% TFA. Wavelength 254 nm.

[0264] Preparative HPLC was performed on a Gilson 215. Flow: 25 mL/min Column: XBrige prep C.sub.18 10 μm OBD (19×250 mm) column. Wavelength: 254 nM. Solvent A water (10 mM Ammonium hydrogen carbonate) and solvent B Acetonitrile. Alternatively preparative HPLC were acquired on a Gilson system. Flow: 15 ml/min Column kromasil 100-5-C18 column Wavelength: 220 nm. Solvent A water+0.1% TFA and solvent B Acetonitrile+0.1% TFA.

[0265] The following abbreviations are used [0266] aq: aqueous [0267] Calcd: Calculated [0268] DCM: dichloromethane [0269] DIEA: N,N-Diisopropylethylamine [0270] DMAP: 4-dimethylaminopyridine [0271] DMF: N,N-dimethylformamide [0272] ESI-MS: Electrospray ionization mass spectrometry [0273] EtOAc: ethyl acetate [0274] h: hours [0275] MeCN: acetonitrile [0276] mM: minutes [0277] nd: not determined [0278] prep. preparative [0279] PE: petroleum ether [0280] rt: Room temperature [0281] TBS: tert-Butyldimethylsilyl [0282] TB AF: tetrabutylammonium Fluoride [0283] TFA: trifluoroacetic acid [0284] TMS: trimethyl silyl UV: Ultraviolet

Example 1

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-phospho-1-thio-α-D-galactopyranoside

[0285] ##STR00059##

5-Bromopyridin-3-yl 4,6-O-benzyliden-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-phospho-1-thio-α-D-galactopyranoside

[0286] ##STR00060##

[0287] To a solution of 5-bromopyridin-3-yl 4,6-O-benzyliden-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (200 mg, 0.322 mmol) and DMAP (78.6 mg, 0.644 mmol) in DCM (15.0 mL) under Na atmosphere at 0° C. was added DIEA (1.38 mL, 8.05 mmol) followed by POCl.sub.3 (0.147 mL, 1.61 mmol) dropwise. After TLC showed no remaining starting material the solvent was removed under vacuo at rt and ammonium hydroxide (15 mL) was added, white solid precipitated out which was collected by filtration and was used directly to the next step without further purification. ESI-MS m/z calcd for [C.sub.26H.sub.21BrF.sub.3N.sub.4).sub.7PS] [M−H].sup.−; 699.0; found: 698.9.

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-phospho-1-thio-α-D-galactopyranoside

[0288] ##STR00061##

[0289] 5-Bromopyridin-3-yl 4,6-O-benzyliden-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-phospho-1-thio-α-D-galactopyranoside (220 mg, 0.314 mmol) was dissolved in 10% TFA in DCM and the reaction was stirred for 3 h. The solvent was removed, and the residue was purified by preparative HPLC to give the title compound (63.4 mg, 33%). ESI-MS m/z calcd for [C.sub.19H.sub.17BrF.sub.3N.sub.4O.sub.7PS] [M−H].sup.−: 611.0; found: 610.8. .sup.1H NMR (400 MHz, MeOD) δ 8.71 (d, J=1.7 Hz, 1H), 8.63 (s, 1H), 8.55 (d, J=2.0 Hz, 1H), 8.38 (t, J=1.9 Hz, 1H), 7.66 (dd, J=8.8, 6.7 Hz, 2H), 6.24 (d, J=5.3 Hz, 1H), 5.43-5.31 (m, 1H), 5.13 (dd, J=11.5, 2.7 Hz, 1H), 4.55 (t, J=5.9 Hz, 1H), 4.22 (s, 1H), 3.77-3.65 (m, 2H).

Example 2

3,4-Dichlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-phospho-1-thio-α-D-galactopyranoside

[0290] ##STR00062##

3,4-Dichlorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0291] ##STR00063##

[0292] To a solution of 3,4-dichlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (605 mg, 1.16 mmol) in dry MeCN (24 mL), benzaldehyde dimethylacetal (0.87 mL, 5.79 mmol) and camphorsulfonic acid (30 mg, 0.12 mmol) dissolved in dry MeCN (1 mL) was added. The transparent yellow mixture was left stirring at rt. After 20 min the reaction mixture became turbid of white precipitate. After 2 h the reaction was stopped by evaporation of solvent. The reaction crude was dissolved in EtOH (180 mL) under heating and left at rt. for 36 h to crystalize. The formed crystals were filtered off and dried under vacuum to obtain the title compound (247 mg, 35%) as amorphous white solid. .sup.1H NMR ((CD.sub.3).sub.2SO, 400 MHz): δ 8.85 (s, 1H, Ph), 7.84-7.76 (m, 3H, Ph), 7.63 (d, J=8.6 Hz, 1H, Ph), 7.52 (dd, J=8.6, 2.1 Hz, 1H, Ph), 7.39-7.30 (m, 5H, Ph), 6.17 (d, J=5.3 Hz, 1H, H-1), 6.10 (d, J=4.8 Hz, 1H, OH-2), 5.57 (s, 1H, CH), 5.09 (dd, J=11.0, 3.1 Hz, 1H, H-3), 4.90 (m, 1H, H-2), 4.56 (d, J=2.9 Hz, 1H, H-4), 4.26 (s, 1H, H-5), 4.13 (d, J=12.5 Hz, 1H, H-6), 3.96 (d, J=12.5 Hz, 1H, H-6). .sup.13C NMR ((CD.sub.3).sub.2SO, 100 MHz): δ 137.8, 135.1, 131.7, 131.5, 130.9, 130.7, 129.4, 128.7, 128.0, 125.9, 122.8, 109.5, 109.3, 99.4, 88.2, 74.1, 68.3, 64.2, 63.1, 61.5. HRMS calculated for [C.sub.27H.sub.21F.sub.3Cl.sub.2N.sub.3O.sub.4S].sup.+, 610.0582; found: 610.0575.

3,4-Dichlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-phospho-1-thio-α-D-galactopyranoside

[0293] ##STR00064##

[0294] Imidazole and 3,4-dichlorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside was rendered anhydrous by co-evaporation with toluene. PCl.sub.3 (0.10 mL, 1.18 mmol) in dry MeCN:DCM 1:1 (4 mL) was cannulated into a stirring solution of imidazole (380 mg, 5.50 mmol) in dry MeCN:DCM 1:1 (6 mL) under N.sub.2-atmosphere. The reaction mixture turned white/light green and turbid. Directly following, Et.sub.3N (0.44 mL, 3.15 mmol) in dry MeCN:DCM 1:1 (4 mL) was cannulated into the stirring solution. 3,4-dichlorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (240 mg, 0.39 mmol) dissolved in dry MeCN:DCM 1:1 (50+10 mL) and was slowly cannulated into the stirring solution over 25 min. The reaction mixture was stirred at 0° C. for 45 min before pyridine:H.sub.2O 4:1 (50 mL) was added. TLC showed complete consumption of starting material. The reaction crude was concentrated and purified by column chromatography (SiO.sub.2, DCM:MeOH 10:1 with 1% Et.sub.3N). The phosphonate was dissolved in dry pyridine (9 mL). TMS-Cl (0.5 mL, 3.93 mmol) was added and the reaction left stirring at r.t. for 5 min before iodine (205 mg, 0.79 mmol) in dry pyridine (1 mL) was added. After stirring for 10 min, water (0.35 mL) was added and the solvent was evaporated. The reaction crude was purified by repeated column chromatography (SiO.sub.2, DCM:MeOH:H.sub.2O 10:1:0->65:35:1). The resulting solid material was dissolved in HOAc (70% aq., 20 mL) and left stirring at 40° C. After 30 h the solvent was evaporated and the crude purified by column chromatography (SiO.sub.2, DCM:MeOH:H.sub.2O 5:1:0->65:35:1) to give the title compound (48 mg, 20%) as amorphous white solid. 41 NMR (MeOD, 400 MHz): δ 8.55 (s, 1H, Ph), 7.64 (dd, J=9.0, 6.8 Hz, 2H, Ph) 7.57 (dd, J=8.4, 2.2 Hz, 1H, Ph), 7.49 (d, J=8.4 Hz, 1H, Ph), 6.08 (d, J=5.4 Hz, 1H, H-1), 5.41 (m, 1H, H-2), 5.17 (dd, J=11.5, 2.9 Hz, 1H, H-3) 4.57 (t, J=6.3 Hz, 1H, H-5), 4.23 (m, 1H, H-4), 3.73 (m, 2H, H-6). .sup.13C NMR (MeOD, 100 MHz): δ 135.3, 135.3, 133.6, 133.0, 131.9, 123.2, 111.0, 110.8, 89.2, 73.6, 71.0, 69.9, 64.3, 64.2, 64.1. HRMS calculated for [C.sub.20H.sub.18F.sub.3Cl.sub.2N.sub.3O.sub.7PS].sup.+, 601.9932; found: 601.9934.

Example 3

3,4-Dichlorphenyl 3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-sulfo-1-thio-α-D-galactopyranoside

[0295] ##STR00065##

[0296] 3,4-Dichlorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (225 mg, 0.37 mmol) and sulfur trioxide-triethylamine complex (560 mg, 3.82 mmol) were dissolved in dry DMF (20 mL) and stirred at 50° C. After 30 h the solvents were evaporated of solvent and the reaction crude purified by column chromatography (SiO.sub.2, EtOAc:Heptane 9:1->1:0). Partial desulfation during evaporation of solvent after column chromatography was observed. The crude was dissolved in HOAc (90% aq., 30 mL) and left stirring at 40° C. for 22 h followed by evaporation of the solvent. The crude was purified by column chromatography (SiO.sub.2, EtOAc:Hep 1:1->EtOAc:Hep 1:0) to give the title compound (48 mg, 22%) as amorphous white solid. .sup.1H NMR (MeOD, 400 MHz): δ 8.56 (s, 1H, Ph), 7.83 (d, J=2.1 Hz, 1H, Ph), 7.62 (dd, J=9.0, 6.3 Hz, 2H, Ph), 7.57 (dd, J=8.3, 2.1 Hz, 1H, Ph), 7.48 (d, J=8.3 Hz, 1H, Ph), 6.24 (d, J=5.3 Hz, 1H, H-1), 5.48 (dd, J=11.7, 5.3 Hz, 1H, H-2), 5.13 (dd, J=11.7, 2.9 Hz, 1H, H-3), 4.56 (t, J=6.1 Hz, 1H, H-5), 4.26 (d, J=2.8 Hz, 1H, H-4), 4.12 (d, J=7.2 Hz, 1H, H-6), 4.08 (d, J=7.2 Hz, 1H, H-6).

Example 4

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-sulfo-1-thio-α-D-galactopyranside

[0297] ##STR00066##

5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0298] ##STR00067##

[0299] To a stirred solution of 5-bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (200 mg, 0.38 mmol) in DMF (10 mL) was added benzaldehyde dimethyl acetal (285 mg, 1.88 mmol) followed by D(+)-10-Camphorsulfonic acid (17.4 mg, 0.075 mmol). The resulting mixture was stirred at 50° C. for 3 h under vacuum. LCMS showed full consumption of starting material and a resulting product spot. The solution was added to aq NaHCO.sub.3 (100 mL) dropwise with vigorous stirring. Then it was filtrated and washed with water to give the title compound (220 mg, 94%) as a white solid. ESI-MS m/z calcd for [C.sub.26H.sub.20BrF.sub.3N.sub.4O.sub.4S] [M+H].sup.+: 621.0; found: 621.1. .sup.1H NMR (400 MHz, DMSO) δ 8.86 (s, 1H), 8.67 (d, J=1.5 Hz, 1H), 8.62 (d, J=1.9 Hz, 1H), 8.28 (s, 1H), 7.87-7.72 (m, 2H), 7.35 (dt, J=9.8, 4.9 Hz, 5H), 6.25 (d, J=5.2 Hz, 1H), 6.17 (d, J=4.8 Hz, 1H), 5.57 (s, 1H), 5.12 (dd, J=11.3, 3.2 Hz, 1H), 4.91 (dd, J=10.9, 5.4 Hz, 1H), 4.57 (d, J=2.9 Hz, 1H), 4.29 (s, 1H), 4.12 (d, J=12.2 Hz, 1H), 3.92 (d, J=12.7 Hz, 1H).

5-Bromopyridin-3-yl 3-Deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-sulfo-1-thio-α-D-galactopyranoside

[0300] ##STR00068##

[0301] 5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (50 mg, 0.081 mmol) and sulfur trioxide trimethylamine complex (224 mg, 1.61 mmol) were dissolved in anhydrous DMF (4.0 mL), the mixture was stirred at rt overnight under Na followed by purification by preparative HPLC. The obtained material was dissolved in CH.sub.3CO.sub.2H (1.60 mL) and H.sub.2O (0.40 mL). The reaction was stirred at 50° C. for 4 h. The solvent was removed, and the residue was purified by preparative HPLC to give the title compound (3.2 mg, 6%). ESI-MS m/z calcd for [C.sub.19H.sub.16BrF.sub.3N.sub.4O.sub.7S.sub.2] [M−H].sup.−: 611.0; found: 611.0. .sup.1H NMR (400 MHz, MeOD) δ 8.71 (s, 1H), 8.56 (s, 2H), 8.35 (s, 1H), 7.75-7.49 (m, 2H), 6.26 (d, J=5.3 Hz, 1H), 5.49 (dd, J=11.7, 5.3 Hz, 1H), 5.16 (dd, J=11.8, 2.6 Hz, 1H), 4.56 (dd, J=13.5, 7.6 Hz, 1H), 4.27 (s, 1H), 3.71 (d, J=6.0 Hz, 2H).

Example 5

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(phosphonooxy)methyl]-1-thio-α-D-galactopyranoside

[0302] ##STR00069##

5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(ditert-butyl-phosphonooxy)methyl]-1-thio-α-D-galactopyranoside

[0303] ##STR00070##

[0304] 5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (200 mg, 0.32 mmol), silver oxide (149 mg, 0.64 mmol), NaI (96.5 mg, 0.64 mmol) and molecular sieves 4 Å (500 mg) were dissolved in DMF (6 mL) under a nitrogen atmosphere. Ditert-butyl chloromethyl phosphate (167 mg, 0.644 mmol) in DMF (0.5 mL) was added. The reaction was stirred overnight at rt and LCMS showed all starting material consumed. The reaction was filtered through Celite® and the solvent was removed. The residue was purified by preparative HPLC to give the title compound (260 mg, 96%) as white solid. .sup.1H NMR (400 MHz, DMSO) δ 8.73 (s, 1H), 8.70 (d, J=1.9 Hz, 1H), 8.68 (d, J=2.1 Hz, 1H), 8.30 (t, J=2.0 Hz, 1H), 7.72 (dd, J=8.9, 6.7 Hz, 2H), 7.34 (s, 5H), 6.40 (d, J=5.1 Hz, 1H), 5.62 (s, 1H), 5.30 (dd, J=11.6, 3.2 Hz, 1H), 5.19 (dd, J=9.8, 5.7 Hz, 1H), 5.13 (dd, J=9.8, 5.8 Hz, 1H), 5.04 (dd, J=11.5, 5.2 Hz, 1H), 4.65 (d, J=3.1 Hz, 1H), 4.42 (s, 1H), 4.14 (d, J=11.6 Hz, 1H), 4.01 (d, J=11.7 Hz, 1H), 1.31 (d, J=4.0 Hz, 18H).

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(phosphonooxy)methyl]-1-thio-α-D-galactopyranoside

[0305] ##STR00071##

[0306] 5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(ditert-butyl-phosphonooxy)methyl]-1-thio-α-D-galactopyranoside (210 mg, 0.25 mmol) was dissolved in 10% (v/v) TFA in DCM and the reaction mixture was stirred for 4 h. LCMS indicated consumption of all starting material and that the product was the main peak. Solvent was removed and the residue was purified by preparative HPLC to give (73.6 mg, 46%) as a white solid. ESI-MS m/z calcd for [C.sub.20H.sub.19BrF.sub.3N.sub.4O.sub.8PS] [M−H].sup.+: 643.0; found: 643.1. .sup.1H NMR (400 MHz, MeOD) δ 8.79-8.64 (m, 2H), 8.54 (d, J=2.0 Hz, 1H), 8.37 (s, 1H), 7.79-7.61 (m, 2H), 6.36 (d, J=5.1 Hz, 1H), 5.20 (dd, J=11.6, 5.2 Hz, 1H), 5.16-5.08 (m, 2H), 4.94-4.89 (m, 1H), 4.48 (t, J=5.9 Hz, 1H), 4.18 (s, 1H), 3.76-3.59 (m, 2H).

Example 6

3,4-Dichlorphenyl 2-O-carboxymethyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0307] ##STR00072##

3,4-Dichlorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-(methoxycarbonyl)methyl-1-thio-α-D-galactopyranoside

[0308] ##STR00073##

[0309] 3,4-Dichlorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (200 mg, 0.33 mmol) and NaH (60% in oil, 20 mg, 0.52 mmol) were dissolved in dry DMF (21 mL) and left stirring at rt. After 30 min methylbromoacetate (0.06 mL, 0.66 mmol) was added to the solution and the temperature was increased to 50° C. and left stirring for 21 h. Approx. 50% of the solvent was evaporated and the remaining crude was diluted with DCM (30 mL) and 0.5 M citric acid was added (30 mL). The organic phase was washed with water (3×30 mL) and then dried. The residue was purified using column chromatography (SiO.sub.2, Heptane:EtOAc 4:1) to give the title compound (88 mg, 39%) as amorphous white solid. .sup.1H NMR (CDCl.sub.3, 400 MHz): δ 8.36 (s, 1H, Ph), 8.64 (d, J=2.1 Hz, 1H, Ph), 7.79 (dd, J=8.5, 6.6 Hz, 2H, Ph), 7.41 (d, J=8.4 Hz, 1H, Ph), 7.37 (s, 5H, Ph), 7.35 (dd, J=8.5, 2.1 Hz, 1H, Ph), 6.22 (d, J=5.1 Hz, 1H, H-1), 5.51 (s, 1H, CH), 5.31 (dd, J=11.3, 3.3 Hz, 1H, H-3), 4.98 (dd, J=11.2, 5.1 Hz, 1H, H-2), 4.57 (d, J=3.2 Hz, 1H, H-4), 4.34 (s, 1H, H-5), 4.31 (dd, J=12.7, 1.8 Hz, 1H, H-6), 4.16 (dd, J=12.7, 1.8 Hz, 1H, H-6), 4.11 (d, J=17.2, 1H, CH.sub.2), 4.02 (d, J=17.2 Hz, 1H, CH.sub.2), 3.68 (s, 3H, CH.sub.3). .sup.13C NMR ((CD.sub.3).sub.2SO, 100 MHz): δ 170.0, 136.9, 133.4, 132.2, 132.0, 131.0, 130.1, 129.4, 128.5, 125.8, 121.5, 110.0, 109.8, 100.8, 85.9, 75.1, 72.0, 69.1, 65.6, 63.5, 61.0, 52.3. HRMS calculated for [C.sub.30H.sub.25F.sub.3Cl.sub.2N.sub.3O.sub.6S].sup.+, 682.0793; found: 682.0792.

3,4-Dichlorophenyl 2-O-carboxymethyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0310] ##STR00074##

[0311] 3,4-Dichlorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-(methoxycarbonyl)methyl-1-thio-α-D-galactopyranoside (52 mg, 0.072 mmol) was dissolved in HOAc (90% aq., 50 mL) and left stirring at 40° C. After 19 h the heating was increased to 90° C. and the reaction left to stir for an additional 3 h before the solvent was evaporated. The remaining crude was dissolved in THF:H.sub.2O (10:1, 16.5 mL) together with LiOH (40 mg, 1.67 mmol) and left stirring 1 h before being quenched by Dowex 50W-X8 (H.sup.+) resin and purified using column chromatography (SiO.sub.2, EtOAc:Hep 3:1) to give the title compound (33 mg, 75%) as amorphous white solid. .sup.1H NMR (MeOD, 400 MHz): δ 8.79 (s, 1H, Ph), 7.82 (d, J=2.1 Hz, 1H, Ph), 7.62 (dd, J=9.0, 6.7 Hz, 2H, Ph), 7.56 (dd, J=8.4, 2.1 Hz, 1H, Ph), 7.48 (d, J=7.4 Hz, 1H, Ph), 6.24 (d, J=5.2 Hz, 1H, H-1), 5.07 (dd, J=11.3, 2.9 Hz, 1H, H-3), 4.95 (dd, J=11.3, 5.4 Hz, 1H, H-2), 4.49 (t, J=6.1 Hz, 1H, H-5), 4.27 (d, J=2.5 Hz, 1H, H-4), 4.24 (d, J=16.9 Hz, 1H, CH2), 4.18 (d, J=16.9 Hz, 1H, CH2), 3.73 (dd, J=11.6, 5.7 Hz, 1H, H-6), 3.68 (dd, J=11.6, 6.7 Hz, 1H, H-6). .sup.13C NMR (MeOD, 100 MHz): δ 173.1, 145.3, 135.3, 135.2, 133.6, 133.4, 132.7, 131.8, 123.9, 110.9, 110.6, 87.7, 73.8, 73.3, 69.8, 66.7, 64.5, 62.1. HRMS calculated for [C.sub.22H.sub.19F.sub.3Cl.sub.2N.sub.3O.sub.6S].sup.+, 580.0324; found: 580.0321.

Example 7

3,4-Dichlorphenyl 2-O-carboxymethyl-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0312] ##STR00075##

3,4-Dichlorophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0313] ##STR00076##

[0314] Copper(II) sulfate pentahydrate (127 mg, 0.5 mmol) was dissolved in hot water (5.0 mL) and added to (+)-sodium L-ascorbate (198 mg, 1.0 mmol). The resulting brownish dispersion was added to a mixture of 3,4-dichlorophenyl 3-azido-3-deoxy-1-thio-α-D-galactopyranoside (2.33 g, 4.7 mmol), K.sub.2CO.sub.3 (6.5 g, 47 mmol), and trimethyl-[2-(4-chloro-3,5-difluorophenyl)ethynyl]silane (1.40 g, 5.68 mmol) in MeOH (20 mL) and THF (20 mL). The resulting mixture was stirred 20 h at 50° C., celite was added, the mixture was filtered, and the filter cake was washed with EtOAc/MeOH. The filtrate was partitioned between EtOAc and aqueous HCl (0.5 M), the organic phase was concentrated. The residue was purified by chromatography (SiO.sub.2, PE/EtOAc) and the crude was triturated in MeCN (30 mL) to give the product (1.73 g, 68%). ESI-MS m/z calcd for [C.sub.20H.sub.16Cl.sub.3F.sub.2N.sub.3O.sub.4S] [M+H].sup.+: 538.0; found: 538.0. .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.60 (s, 1H), 7.80 (d, J=2.0 Hz, 1H), 7.67 (d, J=8.0 Hz, 2H), 7.54 (dd, J=8.4, 2.0 Hz, 1H), 7.48 (d, J=8.4 Hz, 1H), 5.85 (d, J=5.2 Hz, 1H), 4.99 (dd, J=11.4, 2.7 Hz, 1H), 4.96-4.90 (m, 1H), 4.49 (t, J=6.0 Hz, 1H), 4.20 (d, J=1.9 Hz, 1H), 3.77-3.66 (m, 2H).

3,4-Dichlorophenyl 4,6-O-benzylidene-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside

[0315] ##STR00077##

[0316] To a solution of 3,4-dichlorophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (1.73 g, 3.2 mmol) in MeCN (40 mL) benzaldehyde dimethylacetal (0.974 mL, 6.46 mmol) followed by p-toluenesulfonic acid monohydrate (50 mg, 0.26 mmol) were added. The suspension was stirred 72 h at rt, then cooled to 0° C. and filtered to give the product (1.876 g, 93%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.92 (s, 1H), 7.86-7.75 (m, 3H), 7.63 (d, J=8.5 Hz, 1H), 7.52 (dd, J=8.5, 2.0 Hz, 1H), 7.35 (dt, J=11.3, 3.9 Hz, 5H), 6.18 (d, J=5.2 Hz, 1H), 6.13 (d, J=4.7 Hz, 1H), 5.57 (s, 1H), 5.10 (dd, J=11.3, 3.2 Hz, 1H), 4.91 (dt, J=10.9, 5.0 Hz, 1H), 4.56 (d, J=3.0 Hz, 1H), 4.29 (s, 1H), 4.13 (d, J=12.1 Hz, 1H), 3.96 (d, J=12.4 Hz, 1H).

3,4-Dichlorophenyl 4,6-O-benzylidene-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(methoxycarbonyl)methyl-1-thio-α-D-galactopyranoside

[0317] ##STR00078##

[0318] 3,4-Dichlorophenyl 4,6-O-benzylidene-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (800 mg, 1.28 mmol) and NaH (60% in oil, 77 mg, 1.91 mmol) were stirred 5 min in DMF (3.0 mL) before methyl 2-bromoacetate (0.16 mL, 1.66 mmol) was added. The mixture was stirred 2 h at rt and was then poured onto ice cooled water (30 mL) and HCl (4 mL, 1 M). The solids were isolated by filtration and recrystallized from EtOAc/PE to give the product (746 mg, 84%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.97 (s, 1H), 7.86 (d, J=1.9 Hz, 1H), 7.73 (d, J=8.5 Hz, 2H), 7.66 (d, J=8.4 Hz, 1H), 7.54 (dd, J=8.3, 1.8 Hz, 1H), 7.34 (s, 5H), 6.61 (d, J=5.2 Hz, 1H), 5.59 (s, 1H), 5.23 (dd, J=11.5, 3.2 Hz, 1H), 4.87 (dd, J=11.4, 5.1 Hz, 1H), 4.61 (d, J=3.1 Hz, 1H), 4.34 (s, 1H), 4.31 (s, 2H), 4.14 (d, J=12.6 Hz, 1H), 3.99 (d, J=12.5 Hz, 1H), 3.54 (s, 3H).

3,4-Dichlorophenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-carboxymethyl-1-thio-α-D-galactopyranoside

[0319] ##STR00079##

[0320] 3,4-Dichlorophenyl 4,6-O-benzylidene-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-(methoxycarbonyl)methyl-1-thio-α-D-galactopyranoside (721 mg, 1.103 mmol) was stirred 30 min in 80% aq TFA (10 mL), the mixture was concentrated and water was added, which resulted in precipitation. The precipitate was collected by filtration and then stirred 2 h in EtOH (5.0 mL) and NaOH (3.0 mL, 2 M). The mixture was neutralized with HCl (1 M), concentrated, water was added, and pH was adjusted to approximately 1 with HCl (1 M). The precipitate was collected and then triturated in MeOH/water, the solids were collected and to the crude MeOH (3.0 mL) and 28% ammonia (0.20 mL) were added. The mixture was concentrated to dryness, then triturated in Et.sub.2O, the precipitate was collected, and the product was obtained as the ammonium salt (381 mg, 60%). ESI-MS m/z calcd for [C.sub.22H.sub.18Cl.sub.3F.sub.2N.sub.3O.sub.6S] [M+H].sup.+: 596.0; found: 596.1. .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 9.18 (s, 1H), 7.83 (d, J=1.9 Hz, 1H), 7.67 (d, J=8.1 Hz, 2H), 7.57 (dd, J=8.4, 1.8 Hz, 1H), 7.48 (d, J=8.4 Hz, 1H), 6.24 (d, J=3.9 Hz, 1H), 5.05 (m, 2H), 4.48 (t, J=6.1 Hz, 1H), 4.29 (s, 1H), 4.04 (d, J=15.7 Hz, 1H), 3.96 (d, J=15.7 Hz, 1H), 3.76-3.63 (m, 2H).

Example 8

5-Bromopyridin-3-yl 2-O-carboxymethyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0321] ##STR00080##

[0322] 5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (1.00 g, 1.6 mmol) and NaH (60% in oil, 100 mg, 2.4 mmol) were stirred in DMF (5 mL) for 10 min Methyl bromoacetate (230 uL, 2.4 mmol) was added, the mixture was stirred for 1 h, then poured onto ice cooled water (50 mL) and HCl (1 M, 5 mL). The solids were isolated by filtration and then stirred in a mixture of EtOH (20 ml) and 2 M NaOH (4 mL). A gel was formed, the reaction mixture was acidified with HCl and then partitioned between hot EtOAc and water, the organic phase was separated and evaporated. The residue was dissolved in a mixture of formic acid (20 mL) and water (2 mL) and stirred for 2 h at 40° C., then evaporated and hydrolyzed in a mixture of EtOH (20 mL) and 2 M NaOH (4 mL) for 1 h at 40° C. The mixture was concentrated, water was added followed by HCl (pH 1-2), the precipitate was collected by filtration and purified by chromatography (SiO.sub.2, EtOAc/MeOH; 10/1-2/1-0/1). Fractions were collected and gave after evaporation a residue that was dissolved in a mixture of MeOH (10 mL) and ammonium hydroxide (28% aqueous solution, 1 mL). The volatiles were removed, the residue was triturated in diethyl ether and afforded the title compound as the ammonium salt (365 mg, 37%). ESI-MS calcd for [C.sub.21H.sub.18BrF.sub.3N.sub.4O.sub.6S].sup.+ (M+H).sup.+: 591.0; found: 591.1, 1H NMR (400 MHz, Methanol-d4) δ 9.06 (s, 1H), 8.69 (d, J=1.5 Hz, 1H), 8.55 (d, J=1.8 Hz, 1H), 8.36 (s, 1H), 7.72-7.60 (m, 2H), 6.33 (d, J=3.8 Hz, 1H), 5.06 (m, 2H), 4.48 (t, J=6.0 Hz, 1H), 4.29 (s, 1H), 4.05 (d, J=16.0 Hz, 1H), 3.99 (d, J=15.7 Hz, 1H), 3.69 (m, 2H).

Example 9

3,4-Dichlorphenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-[2-(methylsulfonamido)-2-oxoethyl]-1-thio-α-D-galactopyranoside

[0323] ##STR00081##

3,4-Dichlorphenyl 4,6-O-benzylidene-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-[2-(methylsulfonamido)-2-oxoethyl]-1-thio-α-D-galactopyranoside

[0324] ##STR00082##

[0325] To a solution of 3,4-dichlorphenyl 4,6-O-benzylidene-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (130 mg, 0.21 mmol) in DMF (5.0 mL) was added NaH (19.1 mg, 0.83 mmol) at rt. The mixture was stirred for 30 min and 2-chloro-N-methylsulfonyl-acetamide (214 mg, 1.24 mmol) was added in one portion. The reaction was stirred overnight, before being extracted with EtOAc three times. The organic phases were evaporated and purified by silica gel chromatography to give the title compound (106 mg, 67%). ESI-MS calcd for [C.sub.30H.sub.25Cl.sub.3F.sub.2N.sub.4O.sub.7S.sub.2] [M+H].sup.+:761.0; found: 760.9. .sup.1H NMR (400 MHz, CDCl3) δ 8.29 (s, 1H), 7.59 (s, 1H), 7.48-7.28 (m, 9H), 6.13 (d, J=5.0 Hz, 1H), 5.48 (s, 1H), 5.33-5.18 (m, 1H), 4.84 (dd, J=11.1, 5.1 Hz, 1H), 4.51 (s, 1H), 4.31 (s, 1H), 4.18 (dd, J=47.4, 12.9 Hz, 2H), 3.98 (dd, J=35.8, 16.0 Hz, 2H), 3.12 (s, 3H).

3,4-Dichlorphenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-[2-(methylsulfonamido)-2-oxoethyl]-1-thio-α-D-galactopyranoside

[0326] ##STR00083##

[0327] 3,4-Dichlorphenyl 4,6-O-benzylidene-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-[2-(methylsulfonamido)-2-oxoethyl]-1-thio-α-D-galactopyranoside (100 mg, 0.13 mmol) was dissolved in TFA/DCM (1/20) and the solution was stirred for 2 h at rt. The solvent was removed under vacuum and the residue was purified by preparative HPLC to give the title compound (12.0 mg, 14%). ESI-MS calcd for [C.sub.23H.sub.21Cl.sub.3F.sub.2N.sub.4O.sub.7S.sub.2] [M+H].sup.+: 673.0; found: 672.9. .sup.1H NMR (400 MHz, MeOD) δ 8.79 (s, 1H), 7.74 (d, J=1.9 Hz, 1H), 7.59 (d, J=8.1 Hz, 2H), 7.47 (dd, J=8.4, 1.9 Hz, 1H), 7.39 (d, J=8.4 Hz, 1H), 6.14 (d, J=4.9 Hz, 1H), 4.96 (m, 2H), 4.39 (t, J=6.0 Hz, 1H), 4.15 (s, 1H), 4.05 (d, J=4.0 Hz, 2H), 3.60 (dd, J=12.1, 5.2 Hz, 2H), 3.04 (s, 3H).

Example 10

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-(oxazol-4-ylmethyl)-1-thio-α-D-galactopyranoside

[0328] ##STR00084##

[0329] NaH (60% in oil, 38 mg, 1.0 mmol) was added to a solution of oxazol-4-ylmethanol (24 mg, 0.24 mmol) in THF (1 mL) at 0° C., after 45 min methanesulfonyl chloride (28 mg, 0.24 mmol) was added followed, after an additional 15 min, by 5-bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (124 mg, 0.20 mmol) in THF (1 mL). The resulting mixture reached rt in 1 h and was heated 4 h at 40° C. The mixture was diluted with EtOAc, washed with water and brine and the organic phase was dried, evaporated and the residue was purified by chromatography (SiO.sub.2, petroleum ether/EtOAc, 3/1-1/1). The obtained product was treated 30 min with 80% aqueous TFA (1 mL) and the mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (64 mg, 52%). ESI-MS m/z calcd for [C.sub.23H.sub.19BrF.sub.3N.sub.5O.sub.5S] [M+H].sup.+: 614.0; found: 614.0, .sup.1H NMR (400 MHz, Methanol-d4) δ 8.70 (d, J=1.6 Hz, 1H), 8.59 (d, J=1.9 Hz, 1H), 8.46 (s, 1H), 8.37 (t, J=1.8 Hz, 1H), 8.07 (s, 1H), 7.80 (s, 1H), 7.68-7.58 (m, 2H), 6.27 (d, J=5.3 Hz, 1H), 5.08 (dd, J=11.3, 2.7 Hz, 1H), 4.89-4.81 (m, 1H), 4.64 (d, J=12.7 Hz, 1H), 4.53 (d, J=12.7 Hz, 1H), 4.47 (t, J=5.9 Hz, 1H), 4.26-4.19 (m, 1H), 3.76-3.65 (m, 2H).

Example 11

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside

[0330] ##STR00085##

4-(Chloromethyl)-2,6-difluorophenyl methanesulfonate

[0331] ##STR00086##

[0332] 3,5-Difluoro-4-hydroxybenzoic acid (1.00 g, 5.45 mmol), imidazole (1.05 g, 15.26 mmol), and tert-butyldimethylsilyl chloride (3.12 g, 20 mmol) were stirred in DMF (6 mL) for 20 h and then partitioned between ether and water. The organic phase was evaporated, then dissolved in THF (5 mL) and treated with BH.sub.3×THF (15 mL, 15 mmol) at 50° C. for 4 h. The mixture was quenched with MeOH (2 mL), evaporated, and stirred in MeOH at 50° C. for 1 h. Evaporation gave a residue that was partitioned between ether and water at pH 4. The organic phase was evaporated, the residue was dissolved in a mixture of 1 M NaOH and ethanol, aq HCl was added to adjust pH to 1-2 and the mixture was partitioned between diethyl ether and water. The organic phase was evaporated and gave 605 mg material which was mainly 3,5-difluoro-4-hydroxybenzoic acid, .sup.1H NMR (400 MHz, DMSO-d6) δ 13.08 (s, 1H), 11.16 (s, 1H), 7.58-7.47 (m, 2H). This material was refluxed with lithiumaluminium hydride (2 M solution in THF, 4 mL) and THF (4 mL) for 6 h. Workup with water and acetic acid, filtration and extraction (EtOAc/water at pH 4), gave 362 mg of 3,5-difluoro-4-hydroxy-benzylalcohol sufficiently pure for further reactions. .sup.1H NMR (400 MHz, DMSO-d6) δ 10.03 (bs, 1H), 6.94 (m, 2H), 5.23 (bs, 1H), 4.38 (s, 2H). This material (362 mg, 2.27 mmol) was dissolved in DCM (6 mL) and triethylamine (14 mmol, 1.94 mL). Methanesulfonyl chloride (530 uL, 6.8 mmol) was added, the mixture was stirred 18 h, then partitioned between 0.2 M HCl and EtOAc, the organic phase was separated, concentrated and purified by chromatography (SiO.sub.2, EtOAc/PE: 1/1) to give the title compound (339 mg, 1.07 mmol). .sup.1H NMR (400 MHz, Chloroform-d) δ 7.11 (d, J=8.1 Hz, 2H), 4.53 (s, 2H), 3.34 (s, 3H).

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-(3,5-difluoro-4-hydroxybenzyl)-1-thio-α-D-galactopyranoside

[0333] ##STR00087##

[0334] 5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (582 mg, 0.84 mmol) and NaH (60% in oil, 44 mg, 1.1 mmol) were stirred in DMF (3 mL) for 15 min. 4-(Chloromethyl)-2,6-difluorophenyl methanesulfonate (0.74 mmol, 200 mg) in DMF (1 mL) was added and the mixture was stirred for 4 h, then poured onto ice cooled water (20 mL) and HCl (1 M, 2 mL). The solids were isolated by filtration and then stirred in a mixture of MeOH (5 ml), THF (4 mL) and KOH (2 mL, 5 M) for 18 h. The mixture was acidified with HCl (pH 1-2), the solids were isolated by filtration (554 mg). This material was stirred in 80% aq TFA (4 mL) for 2 h, then partitioned between EtOAc/water, the organic phase was separated, dried, and concentrated. Further purification by chromatography (SiO.sub.2, EtOAc/PE; 1/1) gave the crude title compound (111 mg). This material (110 mg) was purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA), pure fractions were analyzed by HPLC and pooled together, crystals precipitated during concentration and gave after collecting the crystals the title compound (69 mg, 14%). ESI-MS m/z calcd for [C.sub.26H.sub.20BrF.sub.5N.sub.4O.sub.5S] [M+H].sup.+: 675.0; found: 675.1, .sup.1H NMR (400 MHz, DMSO-d6) δ 10.10 (s, 1H), 8.75 (s, 1H), 8.71 (d, J=1.4 Hz, 1H), 8.65 (d, J=1.9 Hz, 1H), 8.35 (s, 1H), 7.84-7.71 (m, 2H), 6.73 (d, J=8.0 Hz, 2H), 6.35 (d, J=5.2 Hz, 1H), 5.64 (d, J=6.1 Hz, 1H), 4.95 (dd, J=11.4, 2.5 Hz, 1H), 4.77 (s, 1H), 4.65 (dd, J=11.4, 5.3 Hz, 1H), 4.61 (d, J=11.7 Hz, 1H), 4.39 (d, J=11.7 Hz, 1H), 4.31 (t, J=6.1 Hz, 1H), 4.09 (s, 1H), 3.52 (s, 1H), 3.49-3.38 (m, 1H).

Example 12

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside

[0335] ##STR00088##

[0336] 5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (200 mg, 0.32 mmol) and NaH (60% in oil, 19 mg, 0.48 mmol) were stirred in DMF (2 mL) for 30 min. A solution of 5-(chloromethyl)tetrazole (50 mg, 0.42 mmol) in DMF (1 mL) was added and the mixture was stirred 2 h at rt, then diluted with EtOAc and washed with water and brine. The organic phase was dried, evaporated and the residue was stirred 1 h at rt in 80% aq TFA (3 mL). The mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (87 mg, 44%). ESI-MS m/z calcd for [C.sub.21H.sub.18BrF.sub.3N.sub.8O.sub.4S] [M+H].sup.+: 615.0; found: 615.1, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.66 (s, 1H), 8.60 (s, 1H), 8.42 (s, 1H), 8.35 (s, 1H), 7.62-7.55 (m, 2H), 6.29 (d, J=5.3 Hz, 1H), 5.13 (dd, J=11.3, 2.7 Hz, 1H), 5.07 (d, J=13.6 Hz, 1H), 5.01-4.93 (m, 2H), 4.49 (t, J=6.0 Hz, 1H), 4.21 (d, J=2.4 Hz, 1H), 3.71 (d, J=6.2 Hz, 2H).

Example 13

3,4-Dichlorphenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside

[0337] ##STR00089##

[0338] 3,4-Dichlorophenyl 4,6-O-benzylidene-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (200 mg, 0.32 mmol) and NaH (60% in oil, 31 mg, 0.81 mmol) were stirred in DMF (2 mL) for 15 min. A solution of 5-(chloromethyl)tetrazole (189 mg, 1.60 mmol) in DMF (1.5 mL) was added and the mixture was stirred 4 h at 50° C., then diluted with EtOAc and washed with water and brine. The organic phase was dried, evaporated and the residue was stirred 1 h at rt in 80% aq TFA (4 mL). The mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (17 mg, 9%). ESI-MS calcd for [C.sub.22H.sub.18Cl.sub.3F.sub.2N.sub.7O.sub.4S] [M+H].sup.+: 620.0; found: 620.1, .sup.1H NMR (400 MHz, Methanol-d4) δ 8.47 (s, 1H), 7.78 (s, 1H), 7.60 (d, J=8.0 Hz, 2H), 7.49 (s, 2H), 6.19 (d, J=5.3 Hz, 1H), 5.11 (dd, J=11.4, 2.7 Hz, 1H), 5.04 (d, J=13.6 Hz, 1H), 4.98-4.92 (m, 2H), 4.49 (t, J=6.0 Hz, 1H), 4.20 (s, 1H), 3.76-3.66 (m, 2H).

Example 14

3,4-Dichlorphenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside

[0339] ##STR00090##

[0340] 3,4-Dichlorophenyl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (200 mg, 0.33 mmol) and NaH (60% in oil, 63 mg, 1.64 mmol) were stirred in DMF (2.5 mL) for 30 min A solution of 5-(chloromethyl)tetrazole (58 mg, 0.49 mmol) in DMF (0.5 mL) was added and the mixture was stirred 1 h at 50° C., then diluted with EtOAc and washed with water and brine. The organic phase was dried, evaporated and the residue was stirred 1 h in at rt 80% aq TFA (4 mL). The mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (10 mg, 5%). ESI-MS calcd for [C.sub.22H.sub.18C.sub.12F.sub.3N.sub.7O.sub.4S] [M+H].sup.+: 604.1; found: 604.1, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.42 (s, 1H), 7.77 (s, 1H), 7.64-7.55 (m, 2H), 7.50-7.47 (m, 2H), 6.19 (d, J=5.3 Hz, 1H), 5.10 (dd, J=11.3, 2.6 Hz, 1H), 5.04 (d, J=13.6 Hz, 1H), 4.98-4.91 (m, 2H), 4.49 (t, J=6.0 Hz, 1H), 4.20 (d, J=2.6 Hz, 1H), 3.76-3.66 (m, 2H).

Example 15

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-imidazol-2-yl)methyl]-1-thio-α-D-galactopyranoside

[0341] ##STR00091##

[0342] 5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (150 mg, 0.24 mmol) and NaH (60% in oil, 46 mg, 1.21 mmol) were stirred in DMF (3 mL) 10 min, before 2-(chloromethyl)-1H-imidazole hydrochloride (101 mg, 0.60 mmol) was added. The mixture was stirred 2 h at 40° C., then diluted with EtOAc and washed with water and brine. The organic phase was dried, evaporated and the residue was stirred 1 h at rt in 80% aq TFA (3 mL). The mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (4 mg, 3%). ESI-MS calcd for [C.sub.23H.sub.20BrF.sub.3N.sub.6O.sub.4S] [M+H].sup.+: 613.0; found: 613.1, .sup.1H NMR (400 MHz, Methanol-d4) δ 8.67 (s, 1H), 8.60 (s, 1H), 8.50 (s, 1H), 8.35 (t, J=1.9 Hz, 1H), 7.64-7.57 (m, 2H), 7.44 (s, 2H), 6.26 (d, J=5.3 Hz, 1H), 5.16 (dd, J=11.3, 2.8 Hz, 1H), 5.08-5.00 (m, 2H), 4.88-4.87 (m, 1H), 4.51 (t, J=5.9 Hz, 1H), 4.23 (s, 1H), 3.76-3.67 (m, 2H).

Example 16

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1-methyl-1H-imidazol-2-yl)methyl]-1-thio-α-D-galactopyranoside

[0343] ##STR00092##

[0344] SOCl.sub.2 (106 uL, 1.45 mmol) was added slowly to a solution of (1-methylimidazol-2-yl)methanol hydrochloride (59 mg, 0.36 mmol) in DCM (1 mL) and stirred 10 min at rt. The mixture was evaporated and dried under vacuum. The residue was dissolved in DMF (1 mL) and added to a stirred solution of 5-bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (150 mg, 0.24 mmol) and NaH (60% in oil, 46 mg, 1.21 mmol) were stirred in DMF (2 mL). The mixture was stirred 3 h at 40° C., then diluted with EtOAc and washed twice with water. The organic phase was dried, evaporated and the residue was stirred 40 min at rt in 80% aq TFA (3 mL). The mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (9 mg, 6%). ESI-MS calcd for [C.sub.24H.sub.22BrF.sub.3N.sub.6O.sub.4S] [M+H].sup.+: 627.1; found: 627.1, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.70 (s, 1H), 8.62 (s, 1H), 8.55 (s, 1H), 8.38 (s, 1H), 7.67-7.61 (m, 2H), 7.48 (s, 1H), 7.46 (s, 1H), 6.32 (d, J=5.3 Hz, 1H), 5.17-5.09 (m, 2H), 5.04 (dd, J=11.1, 5.6 Hz, 1H), 4.88-4.87 (m, 1H), 4.51 (t, J=5.9 Hz, 1H), 4.24 (s, 1H), 3.73 (d, J=6.4 Hz, 2H), 3.62 (d, J=4.0 Hz, 3H).

Example 17

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(oxazol-2-yl)methyl]-1-thio-α-D-galactopyranoside

[0345] ##STR00093##

[0346] 5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (150 mg, 0.24 mmol) and NaH (60% in oil, 37 mg, 0.97 mmol) were stirred 5 min in DMF (3 mL), before 2-(chloromethyl)oxazole (62 mg, 0.48 mmol) was added. The mixture was stirred 90 min at 40° C., then diluted with EtOAc and washed with water. The organic phase was dried, evaporated and the residue was stirred 30 min at rt in 80% aq TFA (3 mL). The mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (16 mg, 11%). ESI-MS m/z calcd for [C.sub.23H.sub.19BrF.sub.3N.sub.5O.sub.5S] [M+H].sup.+: 614.0; found: 614.1, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.68 (d, J=1.9 Hz, 1H), 8.60 (d, J=2.1 Hz, 1H), 8.49 (s, 1H), 8.365 (t, J=2.0 Hz, 1H), 7.80-7.77 (m, 1H), 7.63 (dd, J=8.8, 6.6 Hz, 2H), 7.10 (s, 1H), 6.23 (d, J=5.3 Hz, 1H), 5.09 (dd, J=11.3, 2.8 Hz, 1H), 4.94 (dd, J=11.3, 5.3 Hz, 1H), 4.76 (d, J=13.3 Hz, 1H), 4.68 (d, J=13.3 Hz, 1H), 4.48 (t, J=5.9 Hz, 1H), 4.21 (s, 1H), 3.73-3.69 (m, 2H).

Example 18

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(oxazol-5-yl)methyl]-1-thio-α-D-galactopyranoside

[0347] ##STR00094##

[0348] To a solution of 5-bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (300 mg, 0.48 mmol) and NaH (60% in oil, 56 mg, 1.45 mmol) in DMF (2 mL) 5-(bromomethyl)oxazole (195 mg, 1.21 mmol) in DMF (0.5 mL) was added. The mixture was stirred 3 h at 50° C., then diluted with EtOAc and washed with water and brine. The organic phase was dried, evaporated and the residue was purified by chromatography (SiO.sub.2, EtOAc/PE). The product was stirred 1 h at rt in 80% aq TFA (4 mL). The mixture was concentrated and purified by HPLC (Cis, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (121 mg, 41%). ESI-MS m/z calcd for [C.sub.23H.sub.19BrF.sub.3N.sub.5O.sub.5S] [M+H].sup.+: 614.0; found: 614.1, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.70-8.67 (m, 1H), 8.60-8.57 (m, 1H), 8.41-8.39 (m, 1H), 8.37-8.33 (m, 1H), 8.01 (s, 1H), 7.64-7.59 (m, 2H), 7.09 (s, 1H), 6.23 (d, J=5.3 Hz, 1H), 5.07 (dd, J=11.2, 2.7 Hz, 1H), 4.87 (obscured by water, 1H), 4.75 (d, J=13.4 Hz, 1H), 4.62 (d, J=13.4 Hz, 1H), 4.46 (t, J=6.0 Hz, 1H), 4.20 (d, J=2.9 Hz, 1H), 3.76-3.63 (m, 2H).

Example 19

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(isoxazol-3-yl)methyl]-1-thio-α-D-galactopyranoside

[0349] ##STR00095##

[0350] To a solution of 5-bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (352 mg, 0.54 mmol), NaI (82 mg, 0.54 mmol) and 3-(chloromethyl)isoxazole (100 mg, 0.81 mmol) in DMF (2 mL) NaH (60% in oil, 65 mg, 1.62 mmol) was added. The mixture was stirred 2.5 h at 50° C., then poured onto ice cooled water (20 mL) and HCl (1 M, 5 mL). The solids were isolated by filtration and crystallized in MeOH (3 mL), water (1 mL) and 28% NH.sub.3 (one drop). The crystals were isolated and then stirred 1 h at rt in 80% aq TFA (3 mL). The mixture was poured onto ice and NaOH (5 M, 16 mL). The precipitate was isolated by filtration and purified by chromatography (SiO.sub.2, EtOAc/PE). Crystallization of the product from EtOAc/PE gave the title compound (105 mg, 31%). ESI-MS m/z calcd for [C.sub.23H.sub.19BrF.sub.3N.sub.5O.sub.5S] [M+H].sup.+: 614.0; found: 614.1, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.68 (d, J=1.7 Hz, 1H), 8.58 (d, J=2.0 Hz, 1H), 8.49 (s, 1H), 8.34 (t, J=2.0 Hz 1H), 7.63 (m, 2H), 6.26 (d, J=5.3 Hz, 1H), 6.20 (s, 1H), 5.11 (dd, J=11.3, 2.8 Hz, 1H), 4.88 (dd, J=11.3, 5.3 Hz, 1H), 4.83 (d, J=12.6 Hz, 1H), 4.66 (d, J=12.6 Hz, 1H), 4.49 (t, J=6.0 Hz, 1H), 4.21 (d, J=2.6 Hz, 1H), 3.76-3.65 (m, 2H).

Example 20

3,4-Dichlorphenyl 3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-2-O-[(oxazol-4-yl)methyl]-1-thio-α-D-galactopyranoside

[0351] ##STR00096##

[0352] Oxazol-4-ylmethanol (40 mg, 0.38 mmol) was dissolved in THF (1 mL) and cooled to 0° C. before NaH (60% in oil, 61 mg, 1.60 mmol) was added. After 45 min methanesulfonyl chloride (30 μL, 0.38 mmol) was added and after an additional 15 min 3,4-dichlorophenyl 4,6-O-benzylidene-3-[4-(4-chloro-3,5-difluorophenyl)-1H-1,2,3-triazol-1-yl]-3-deoxy-1-thio-α-D-galactopyranoside (200 mg, 0.32 mmol) and THF (1 mL) were added. The mixture reached rt in 1 h and was then stirred 4 h at 40° C. The mixture was diluted with EtOAc (20 mL), washed with water (20 mL) and brine (20 mL) and the organic phase was dried and evaporated. The residue was stirred 1 h at rt in 80% aq TFA (3 mL). Cold water was added and decanted, the residue was coevaporated from isopropanol. The residue was purified by chromatography (SiO.sub.2, EtOAc/PE). The product was further purified by HPLC (Cis, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (36 mg, 16%). ESI-MS m/z calcd for [C.sub.24H.sub.19Cl.sub.3F.sub.2N.sub.4O.sub.5S] [M+H].sup.+: 619.0; found: 619.1, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.74 (s, 1H), 8.25 (s, 1H), 7.91 (s, 1H), 7.86 (d, J=2.0 Hz, 1H), 7.79 (d, J=8.3 Hz, 2H), 7.62 (d, J=8.4 Hz, 1H), 7.54 (dd, J=8.4, 2.0 Hz, 1H), 6.34 (d, J=5.1 Hz, 1H), 5.59 (d, J=6.2 Hz, 1H), 4.90 (dd, J=11.4, 2.7 Hz, 1H), 4.76-4.67 (m, 3H), 4.59 (d, J=12.6 Hz, 1H), 4.50 (d, J=12.6 Hz, 1H), 4.27 (t, J=5.9 Hz, 1H), 4.12-4.03 (m, 1H), 3.52 (m, 1H), 3.43 (m, 1H).

Example 21

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-4-yl)methyl]-1-thio-α-D-galactopyranoside

[0353] ##STR00097##

[0354] 5-Bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (200 mg, 0.32 mmol) and NaH (60% in oil, 49 mg, 1.29 mmol) were stirred 10 min in DMF (3 mL), before 4-(chloromethyl)thiazole hydrochloride (90 mg, 0.48 mmol) was added. The mixture was stirred 3 h at 40° C., then diluted with EtOAc and washed with water and brine. The organic phase was dried, evaporated and the residue was stirred 1 h at rt in 80% aq TFA (3 mL). The mixture was concentrated and purified by chromatography (SiO.sub.2, EtOAc/PE). The product was further purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (75 mg, 37%). ESI-MS m/z calcd for [C.sub.23H.sub.19BrF.sub.3N.sub.5O.sub.4S.sub.2] [M+H].sup.+: 630.0; found: 630.1, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.89 (d, J=1.9 Hz, 1H), 8.68 (d, J=1.9 Hz, 1H), 8.59 (d, J=2.1 Hz, 1H), 8.35 (d, J=1.9 Hz 1H), 7.64-7.57 (m, 2H), 6.22 (d, J=5.3 Hz, 1H), 5.10 (dd, J=11.3, 2.7 Hz, 1H), 4.91-4.86 (m, 1H), 4.71 (d, J=12.5 Hz, 1H), 4.48 (t, J=6.0 Hz, 1H), 4.22 (s, 1H), 3.75-3.65 (m, 2H).

Example 22

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-5-yl)methyl]-1-thio-α-D-galactopyranoside

[0355] ##STR00098##

[0356] 5-Hydroxymethylthiazole (131 mg, 1.08 mmol) was stirred in DCM (1.5 mL), thionyl chloride (300 uL, 4.0 mmol) was added and the mixture was stirred 10 min at rt. The mixture was evaporated, dried and stirred 5 min together with 5-bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (335 mg, 0.54 mmol) and NaI (162 mg, 1.08 mmol) in DMF (3.0 mL). The mixture was cooled to 0° C. and NaH (60% in oil, 132 mg, 3.3 mmol) was added. The mixture was stirred 2 h at rt, then poured onto ice cooled water (30 mL) and HCl (1 M, 5 mL). The solids were isolated by filtration and then stirred overnight in MeOH (4 mL), water (1 mL) and NH.sub.3 (one drop). The precipitate was isolated by filtration and was then stirred 30 min in 80% aq TFA (4 mL). The mixture was concentrated to approximately 2 mL volume, then poured onto ice and NaOH (1 M, 20 mL). The precipitate was isolated by filtration and then stirred in EtOAc, which resulted in crystallization. The crystals were isolated and recrystallized from HOAc and water to afford the title compound (63 mg, 19%). ESI-MS m/z calcd for [C.sub.23H.sub.19BrF.sub.3N.sub.5O.sub.4S.sub.2] [M+H].sup.+: 630.0; found: 630.1, .sup.1H NMR (400 MHz, Methanol-d4) δ 8.84 (s, 1H), 8.69 (s, 1H), 8.58 (d, J=1.7 Hz, 1H), 8.44 (s, 1H), 8.34 (s, 1H), 7.76-7.57 (m, 2H), 6.25 (d, J=5.3 Hz, 1H), 5.10 (dd, J=11.3, 2.7 Hz, 1H), 5.01 (d, J=12.6 Hz, 1H), 4.86 (dd, J=11.3, 5.3 Hz, 1H), 4.79 (d, J=12.5 Hz, 1H), 4.48 (t, J=6.0 Hz, 1H), 4.21 (s, 1H), 3.76-3.65 (m, 2H).

Example 23

5-Bromopyridin-3-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-2-yl)methyl]-1-thio-α-D-galactopyranoside

[0357] ##STR00099##

[0358] 1,3-Thiazol-2ylmethanol (132 mg, 1.08 mmol) was stirred in DCM (2 mL), thionyl chloride (300 uL, 4.0 mmol) was added and the mixture was stirred 5 min at rt. The mixture was evaporated, dried and stirred together with 5-bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (224 mg, 0.36 mmol) in DMF (3.0 mL). NaH (60% in oil, 160 mg, 4.0 mmol) was added. The mixture was stirred 18 h at rt, then poured onto ice cooled water (20 mL) and HCl (1 M, 5 mL). The solids were isolated by filtration and then purified by chromatography (SiO.sub.2, EtOAc/PE). The product was stirred 1 h in 80% aq TFA (1.5 mL). The mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (35 mg, 13%). ESI-MS m/z calcd for [C.sub.23H.sub.19BrF.sub.3N.sub.5O.sub.4S.sub.2] [M+H].sup.+: 630.0; found: 629.7, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.70 (d, J=1.9 Hz, 1H), 8.59 (d, J=2.1 Hz, 1H), 8.54 (s, 1H), 8.37 (t, J=2.0 Hz, 1H), 7.69 (d, J=3.3 Hz, 1H), 7.66-7.58 (m, 2H), 7.48 (d, J=3.3 Hz, 1H), 6.29 (d, J=5.3 Hz, 1H), 5.15 (dd, J=11.4, 2.8 Hz, 1H), 5.07 (d, J=13.1 Hz, 1H), 4.98 (dd, J=11.3, 5.3 Hz, 1H), 4.83 (d, J=13.1 Hz, 1H), 4.50 (t, J=5.9 Hz, 1H), 4.23 (d, J=2.0 Hz, 1H), 3.77-3.67 (m, 2H).

Example 24

4-Chloro-N,N-dimethyl-benzamide-2-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-4-yl)methyl]-1-thio-α-D-galactopyranoside

[0359] ##STR00100##

5-Chloro-2-cyanophenyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside

[0360] ##STR00101##

[0361] 2,4,6-Tri-0-acetyl-3-azido-3-deoxy-β-D-galactopyranosyl chloride (WO2016120403) (9.6 g, 27.3 mmol), 4-chloro-2-sulfanylbenzonitrile (5.1 g, 30.1 mmol), Cs.sub.2CO.sub.3 (17.8 g, 54.7 mmol) and DMF (40 mL) were stirred 20 h at rt. The mixture was partitioned between diethyl ether/EtOAc/aq HCl/water, the organic phase was separated, concentrated, and the residue was subjected to chromatography (SiO.sub.2, PE/EtOAc) to afford the product (5.63 g, 42%). .sup.1H NMR (400 MHz, Chloroform-d) δ 7.69 (d, J=1.7 Hz, 1H), 7.61 (d, J=8.3 Hz, 1H), 7.39 (dd, J=8.3, 1.9 Hz, 1H), 6.07 (d, J=5.5 Hz, 1H), 5.51 (d, J=2.2 Hz, 1H), 5.31 (dd, J=11.0, 5.5 Hz, 1H), 4.68-4.60 (m, 1H), 4.14 (dd, J=11.7, 5.1 Hz, 1H), 4.05 (dd, J=11.6, 7.6 Hz, 1H), 3.99 (dd, J=11.0, 3.2 Hz, 1H), 2.23 (s, 3H), 2.17 (s, 3H), 2.02 (s, 3H).

5-Chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0362] ##STR00102##

[0363] 5-Chloro-2-cyanophenyl 2,4,6-tri-O-acetyl-3-azido-3-deoxy-1-thio-α-D-galactopyranoside (454 mg, 0.94 mmol), trimethyl-[2-(3,4,5-trifluorophenyl)ethynyl]silane (429 mg, 1.88 mmol) and K.sub.2CO.sub.3 (1.30 g, 9.41 mmol) were weighed into a glass flask and purged with nitrogen. MeOH (5.0 mL) and THF (5.0 mL) were added followed by a solution of copper(II) sulfate pentahydrate (40 mg, 0.16 mmol) and (+)-sodium L-ascorbate (70 mg, 0.35 mmol) in water (2.5 mL). The mixture was stirred 8 h at 60° C. and then copper(II) sulfate pentahydrate (40 mg, 0.16 mmol) and (+)-sodium L-ascorbate (70 mg, 0.35 mmol) were added. Stirring was continued for 4 h at 60° C. The mixture was filtered through a pad of silica eluted with EtOAc and concentrated. The residue was purified by chromatography (SiO.sub.2, PE/EtOAc) to afford a residue that was recrystallized first from EtOAc/hexanes and then from EtOH and water to give the product (248 mg, 51%). ESI-MS m/z calcd for [C.sub.21H.sub.16ClF.sub.3N.sub.4O.sub.4S] [M+H].sup.+: 513.06; found: 513.1. .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.55 (s, 1H), 7.98 (d, J=1.8 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.71-7.61 (m, 2H), 7.47 (dd, J=8.4, 1.9 Hz, 1H), 6.13 (d, J=5.1 Hz, 1H), 5.06 (dd, J=11.4, 2.6 Hz, 1H), 4.99 (dd, J=11.4, 5.2 Hz, 1H), 4.42 (t, J=6.1 Hz, 1H), 4.23 (d, J=2.4 Hz, 1H), 3.71 (dd, J=11.4, 5.6 Hz, 1H), 3.64 (dd, J=11.3, 6.6 Hz, 1H).

2-Carboxy-5-chlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0364] ##STR00103##

[0365] 5-Chloro-2-cyanophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (717 mg, 1.39 mmol) was stirred 5 h under nitrogen at 80° C. in a mixture of EtOH (36 mL) and NaOH (18 mL, 3 M). The mixture was concentrated to approximately 25 mL and acidified to approximately pH 1 with HCl (5 M). The precipitate was isolated by filtration and gave the product (702 mg, 95%). .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.55 (s, 1H), 7.96-7.88 (m, 2H), 7.70-7.59 (m, 2H), 7.29 (d, J=8.4 Hz, 1H), 6.00 (d, J=5.4 Hz, 1H), 5.09 (dd, J=11.5, 2.7 Hz, 1H), 4.99 (dd, J=11.4, 5.4 Hz, 1H), 4.42 (t, J=6.2 Hz, 1H), 4.22 (s, 1H), 3.76 (dd, J=11.3, 6.0 Hz, 1H), 3.67 (dd, J=11.2, 6.3 Hz, 1H).

4-Chloro-N,N-dimethyl-benzamide-2-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0366] ##STR00104##

[0367] 2-Carboxy-5-chlorophenyl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (473 mg, 0.82 mmol), 1-hydroxybenzotriazole hydrate (195 mg, 1.23 mmol) and N-β-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (243 mg, 1.23 mmol) were stirred in DMF (3 mL) and dimethylamine (0.82 mL, 2M solution in THF, 1.64 mmol) was added followed by DIEA (0.14 mL, 0.82 mmol). The mixture was stirred 6 h at rt, then water (20 mL) was added and decanted. The residue was stirred in EtOH (5 mL) and NaOH (1.0 mL, 2 M) 1 h at rt, then poured onto ice/water and HCl. The precipitate was collected by filtration and purified by chromatography (SiO.sub.2, PE/EtOAc) to afford the product (268 mg, 58%). ESI-MS m/z calcd for [C.sub.23H.sub.22ClF.sub.3N.sub.4O.sub.5S] [M+H].sup.+: 559.1; found: 558.7. .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.53 (s, 1H), 7.86 (s, 1H), 7.65 (m, 2H), 7.42 (d, J=8.2 Hz, 1H), 7.27 (d, J=8.2 Hz, 1H), 5.92 (d, J=5.0 Hz, 1H), 4.96 (dd, J=11.4, 2.5 Hz, 1H), 4.90 (dd, J=11.4, 5.0 Hz, 1H), 4.48 (t, J=6.1 Hz, 1H), 4.19 (s, 1H), 3.71 (m, 2H), 3.13 (s, 3H), 2.90 (s, 3H).

4-Chloro-N,N-dimethyl-benzamide-2-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0368] ##STR00105##

[0369] A solution of 4-chloro-N,N-dimethyl-benzamide-2-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-thio-α-D-galactopyranoside (200 mg, 0.36 mmol), benzaldehyde dimethylacetal (110 μL, 1.36 mmol) and p-toluenesulfonic acid monohydrate (5 mg, 0.026 mmol) in MeCN (10 mL) were stirred 20 h at rt. The mixture was concentrated and purified by chromatography (SiO.sub.2, PE/EtOAc) to afford the title compound (216 mg, 93%). ESI-MS calcd for [C.sub.30H.sub.26ClF.sub.3N.sub.4O.sub.5S] [M+NH.sub.3].sup.+: 663.2; found: 663.2. .sup.1H NMR (400 MHz, Chloroform-d) δ 8.04 (d, J=2.4 Hz, 1H), 7.73 (d, J=2.0 Hz, 1H), 7.47-7.41 (m, 2H), 7.39 (dd, J=8.1, 2.1 Hz, 2H), 7.36 (s, 5H), 7.18 (d, J=8.2 Hz, 1H), 5.91 (d, J=4.8 Hz, 1H), 5.49 (s, 1H), 5.14 (dd, J=11.3, 3.1 Hz, 1H), 4.88 (dd, J=11.3, 4.9 Hz, 1H), 4.55 (d, J=2.5 Hz, 1H), 4.41 (d, J=12.7 Hz, 1H), 4.31 (s, 1H), 4.18 (d, J=13.9 Hz, 1H), 3.12 (s, 3H), 2.87 (s, 3H).

4-Chloro-N,N-dimethyl-benzamide-2-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(thiazol-4-yl)methyl]-1-thio-α-D-galactopyranoside

[0370] ##STR00106##

[0371] 4-Chloro-N,N-dimethyl-benzamide-2-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (74 mg, 0.11 mmol) and NaH (60% in oil, 17 mg, 0.45 mmol) were stirred 10 min in DMF (1.5 mL), before 4-(chloromethyl)thiazole hydrochloride (31 mg, 0.17 mmol) was added. The mixture was stirred 2 h at 40° C., then diluted with EtOAc and washed with water and brine. The organic phase was dried, evaporated and the residue was stirred 1 h at rt in 80% aq TFA (2 mL). The mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (24 mg, 32%). ESI-MS m/z calcd for [C.sub.27H.sub.25ClF.sub.3N.sub.5O.sub.5S.sub.2] [M+NH.sub.3].sup.+: 672.1; found: 671.8, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.92 (d, J=1.8 Hz, 1H), 8.45 (s, 1H), 7.87 (s, 1H), 7.61 (d, J=8.0 Hz, 2H), 7.47 (d, J=8.5 Hz, 1H), 7.41 (s, 1H), 7.30 (d, J=8.1 Hz, 1H), 6.25 (d, J=4.7 Hz, 1H), 5.07 (dd, J=11.4, 2.7 Hz, 1H), 4.90-4.86 (m, 1H), 4.81 (dd, J=10.8, 5.2 Hz, 4H), 4.69 (d, J=12.5 Hz, 1H), 4.59-4.52 (m, 1H), 4.23 (s, 1H), 3.76-3.70 (m, 2H), 3.05 (s, 3H), 2.87 (s, 3H).

Example 25

4-Chloro-N,N-dimethyl-benzamide-2-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-2-O-[(1H-tetrazol-5-yl)methyl]-1-thio-α-D-galactopyranoside

[0372] ##STR00107##

[0373] To a solution of 4-chloro-N,N-dimethyl-benzamide-2-yl 3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (53 mg, 0.095 mmol) and p-toluenesulfonic acid monohydrate (3.6 mg, 0.019 mmol) in MeCN (3 mL) benzaldehyde dimethylacetal (29 μL, 0.19 mmol) was added and the mixture was stirred 4 h at rt. The mixture was neutralized with triethylamine (6.5 μL, 0.047 mmol) and concentrated. The residue and NaH (60% in oil, 11 mg, 0.28 mmol) were stirred 20 min in DMF (3 mL), before 5-(chloromethyl)1H-tetrazole (23 mg, 0.19 mmol) was added. The mixture was stirred 2 h at 40° C., then diluted with EtOAc and washed with water and brine. The organic phase was dried, evaporated and the residue was stirred 1 h at rt in 80% aq TFA (2 mL). The mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (20 mg, 33%). ESI-MS m/z calcd for [C.sub.25H.sub.24ClF.sub.3N.sub.8O.sub.5S] [M+H].sup.+: 641.1; found: 641.2, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.42 (s, 1H), 7.89 (s, 1H), 7.62-7.56 (m, 2H), 7.47 (d, J=7.6 Hz, 1H), 7.30 (d, J=8.1 Hz, 1H), 6.28 (d, J=3.2 Hz, 1H), 5.12-5.05 (m, 2H), 4.96-4.88 (m, 2H), 4.57 (t, J=5.2 Hz, 1H), 4.21 (d, J=2.2 Hz, 1H), 3.74 (d, J=6.0 Hz, 2H), 2.99 (s, 3H), 2.83 (s, 3H).

Example 26

5-Bromopyridin-3-yl 2-O-carboxypropyl-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside

[0374] ##STR00108##

[0375] To a solution of 5-bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (888 mg, 1.42 mmol), NaI (454 mg, 3.0 mmol) and tert-butyl 4-bromobutanoate (460 mg, 2.0 mmol) in DMF (10 mL) NaH (60% in oil, 120 mg, 2.86 mmol) was added. The mixture was stirred 20 h at rt, then poured onto ice cooled water (80 mL) and HCl (1 M, 10 mL). The solids were isolated by filtration, then partitioned between EtOAc and water. The organic phase was dried, evaporated and purified by chromatography (SiO.sub.2, EtOAc/PE). The obtained material was triturated in EtOAc/PE (1:1) to give a product that was stirred 45 min at rt in 80% aq TFA (3 mL). The mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA) to afford the title compound (23 mg, 3%). ESI-MS m/z calcd for [C.sub.23H.sub.22BrF.sub.3N.sub.4O.sub.6S] [M+H].sup.+: 619.0; found: 619.1, .sup.1H NMR (400 MHz, DMSO-d6) δ 11.91 (s, 1H), 8.85 (s, 1H), 8.68 (s, 1H), 8.63 (s, 1H), 8.33 (s, 1H), 7.86-7.74 (m, 2H), 6.36 (d, J=5.2 Hz, 1H), 5.59 (d, J=6.1 Hz, 1H), 4.89 (d, J=11.5 Hz, 1H), 4.76 (s, 1H), 4.57 (dd, J=11.3, 5.2 Hz, 1H), 4.28 (d, J=6.1 Hz, 1H), 4.06 (s, 1H), 3.79-3.67 (m, 1H), 3.59-3.47 (m, 1H), 3.47-3.34 (m, 2H), 2.00 (t, J=7.3 Hz, 2H), 1.54 (q, J=6.8 Hz, 2H).

Examples 27 and 28

5-Bromopyridin-3-yl 2-O-(1-carboxy)ethyl)-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (Diastereomer 1)

[0376] ##STR00109##

5-Bromopyridin-3-yl 2-O-(1-carboxy)ethyl)-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (Diastereomer 2)

[0377] ##STR00110##

[0378] To a solution of 5-bromopyridin-3-yl 4,6-O-benzylidene-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (150 mg, 0.24 mmol) and NaH (60% in oil, 14 mg, 0.36 mmol) in DMF (2 mL) 2-bromopropanoate (35 uL, 0.31 mmol) was added. The mixture was stirred 1 h at rt, then diluted with EtOAc and washed with water and brine. The organic phase was dried, evaporated and the residue was stirred 1 h at rt in 80% aq TFA (3 mL). The mixture was concentrated and dissolved together with LiOHxH.sub.2O (50 mg, 1.21 mmol) in THF/H.sub.2O (3.5 mL, 9:1). After stirring 3 h at rt the mixture was concentrated and purified by HPLC (C.sub.18, H.sub.2O/MeCN/0.1% TFA). The two diasteromers were isolated without determining the exact stereochemistry of the 2-O-(1-carboxy)ethyl) substituent. Diasteromer 1 (36 mg, 25%) was eluted first on the C.sub.18 column in the HPLC and diastereomer 2 (34 mg, 23%) eluted second.

5-Bromopyridin-3-yl 2-O-(1-carboxy)ethyl)-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-α-D-galactopyranoside (Diastereomer 1)

[0379] ESI-MS m/z calcd for [C.sub.22H.sub.20BrF.sub.3N.sub.4O.sub.6S] [M+H].sup.+: 605.0; found: 605.1, .sup.1H NMR (400 MHz, Methanol-d.sub.4) δ 8.71-8.67 (m, 2H), 8.57 (d, J=1.6 Hz, 1H), 8.36-8.34 (m, 1H), 7.70-7.63 (m, 2H), 6.24 (d, J=5.3 Hz, 1H), 5.09 (dd, J=11.2, 2.6 Hz, 1H), 4.87-4.83 (m, 1H), 4.49 (t, J=6.0 Hz, 1H), 4.23 (d, J=2.2 Hz, 1H), 3.95 (q, J=6.8 Hz, 1H), 3.76-3.68 (m, 2H), 1.04 (d, J=6.8 Hz, 3H).

5-Bromopyridin-3-yl 2-O-(1-carboxy)ethyl)-3-deoxy-3-[4-(3,4,5-trifluorophenyl)-1H-1,2,3-triazol-1-yl]-1-thio-o-D-galactopyranoside (Diastereomer 2)

[0380] ESI-MS calcd for [C.sub.22H.sub.20BrF.sub.3N.sub.4O.sub.6S] [M+H].sup.+: 605.0; found: 605.1, .sup.1H NMR (400 MHz, Methanol-d4) δ 8.79 (s, 1H), 8.71 (d, J=1.8 Hz, 1H), 8.60 (d, J=2.0 Hz, 1H), 8.39 (t, J=2.0 Hz, 1H), 7.60 (dd, J=8.7, 6.6 Hz, 2H), 6.35 (d, J=5.1 Hz, 1H), 5.11 (dd, J=11.3, 2.8 Hz, 1H), 5.00 (dd, J=11.3, 5.2 Hz, 1H), 4.50-4.45 (m, 1H), 4.43 (q, J=6.8 Hz, 1H), 4.25 (d, J=2.2 Hz, 1H), 3.74-3.63 (m, 2H), 1.38 (d, J=6.8 Hz, 3H).

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