Carbohydrate mimetics having antiadhesive properties
AssigneeGlycorex AB
InventorsAlexander Toepfer, Gerhard Kretzschmar, Eckart Bartnik, Dirk Seiffge
Life of this patent
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Abstract
The invention relates to carbohydrate mimetics, which inhibit the binding of selectin to carbohydrate ligands, of the formula I ##STR1## excluding the compounds sialyl-Lewis-X and -A and their derivatives which, instead of an N-acetyl group, carry the substituents N.sub.3, NH.sub.2 or OH or which, instead of fucose, carry glycerol, and pharmaceutical compositions and diagnostic agents containing these derivatives, and methods for using these pharmaceutical compositions and diagnostic agents.
Claims38
A compound of formula I ##STR30## in which R.sup.1 and R.sup.2 independently of one another are H, CH.sub.2 X or CH.sub.2 O(CH.sub.2).sub.m X.sup.1, wherein X and X.sup.1 independently of one another are H, --NH.sub.2, --COOH, --OH, --CH.sub.2 OH, --CH.sub.2 NH, --(CH.sub.2).sub.r CH.sub.3, aryl, --CH.sub.2 O(CH.sub.2).sub.q H, --CH.sub.2 O(CH.sub.2).sub.q NH.sub.2, --CH.sub.2 O(CH.sub.2).sub.q COOH, --CH.sub.2 O(CH.sub.2).sub.q OH, --CH.sub.2 O(CH.sub.2).sub.q CH.sub.2 OH, --CH.sub.2 O(CH.sub.2).sub.q (CH.sub.2).sub.r CH.sub.3, or --CH.sub.2 O(CH.sub.2).sub.q -Aryl, where r is 0 to 24, or R.sup.1 and R.sup.2 together form a six-membered carbo- or heterocycle which is either unsubstituted or has at least one substituent selected from the group consisting of R.sup.7, R.sup.8 and R.sup.9,
- R.sup.3 and R.sup.6 together form a six-membered carbo- or heterocycle having at least one substituent X.sup.4,
- R.sup.4 and R.sup.5 independently of one another are H, OH, CH.sub.2 OH, O(CR.sup.10 R.sup.11).sub.n COOH, OCX.sup.3.sub.2 (CR.sup.10 R.sup.11).sub.n COOH, or OSO.sub.3 H,
- Y is O-.alpha.-NANA, O-.beta.-NANA, or --O--CH.sub.2 --COOH,
- Z is a pyranose or a furanose,
- m, n, and q independently of one another are integers from 1 to 20,
- R.sup.7, R.sup.8, R.sup.9, and X.sup.4 independently of one another are --NH.sub.2, --COOH, --CH.sub.2 OH, --CH.sub.2 NH, --(CH.sub.2).sub.r CH.sub.3, aryl, --CH.sub.2 O(CH.sub.2).sub.q H, --CH.sub.2 O(CH.sub.2).sub.q NH.sub.2, --CH.sub.2 O(CH.sub.2).sub.q COOH, --CH.sub.2 O(CH.sub.2).sub.q OH, --CH.sub.2 O(CH.sub.2).sub.q CH.sub.2 OH, --CH.sub.2 O(CH.sub.2).sub.q (CH.sub.2).sub.r CH.sub.3, or --CH.sub.2 O(CH.sub.2).sub.q -Aryl, where r is 0 to 24,
- X.sup.3 is H, --(CH.sub.2).sub.r CH.sub.3, or aryl, or alternatively
- X.sup.3.sub.2 is .dbd.O or .dbd.S, and
- R.sup.10 and R.sup.11 independently of one another are X or --CH.sub.2 X or together form a six-membered carbo- or heterocycle having at least one substituent X.sup.4,
- wherein said compound is other than the compounds sialyl-Lewis-X and -A and their derivatives, which derivatives, instead of an N-acetyl group, carry the substituents N.sub.3, NH.sub.2 or OH or which derivatives, instead of fucose, carry glycerol.
A compound of formula I ##STR31## in which R.sup.1 and R.sup.2 together form a six-membered carbo- or heterocycle which is either unsubstituted or has at least one substituent selected from the group consisting of R.sup.7, R.sup.8 and R.sup.9,
- R.sup.3 is .dbd.O, .dbd.S, H or --CH.sub.2 OX.sup.2,
- R.sup.4 and R.sup.5 independently of one another are H, OH, CH.sub.2 OH, O(CR.sup.10 R.sup.11).sub.n COOH, OCX.sup.3.sub.2 (CR.sup.10 R.sup.11).sub.n COOH, or OSO.sub.3 H,
- R.sup.6 is H, --OH or --(CH.sub.2).sub.r CH.sub.3, or, with R.sup.3, forms a six-membered carbo- or heterocycle having at least one substituent X.sup.4,
- Y is O-.alpha.-NANA or O-.beta.-NANA,
- Z is a pyranose or a furanose,
- m, n, and q independently of one another are integers from 1 to 20, and r is 0 to 24,
- R.sup.7, R.sup.8, R.sup.9, and X.sup.4 independently of one another are --NH.sub.2, --COOH, --CH.sub.2 OH, --CH.sub.2 NH, --(CH.sub.2).sub.r CH.sub.3, aryl, --CH.sub.2 O(CH.sub.2).sub.q H, --CH.sub.2 O(CH.sub.2).sub.q NH.sub.2, --CH.sub.2 O(CH.sub.2).sub.q COOH, --CH.sub.2 O(CH.sub.2).sub.q OH, --CH.sub.2 O(CH.sub.2).sub.q CH.sub.2 OH, --CH.sub.2 O(CH.sub.2).sub.q (CH.sub.2).sub.r CH.sub.3, or --CH.sub.2 O(CH.sub.2).sub.q -Aryl,
- X.sup.3 is H, --(CH.sub.2).sub.r CH.sub.3, or aryl or alternatively
- X.sup.3.sub.2 is .dbd.O or .dbd.S,
- R.sup.10 and R.sup.11 independently of one another are X or --CH.sub.2 X or together form a six-membered carbo- or heterocycle having at least one substituent X.sup.4,
- wherein X and X.sup.2 independently of one another are H, --NH.sub.2, --COOH, --OH, --CH.sub.2 OH, --CH.sub.2 NH, --(CH.sub.2).sub.r CH.sub.3, aryl, --CH.sub.2 O(CH.sub.2).sub.q H, --CH.sub.2 O(CH.sub.2).sub.q NH.sub.2, --CH.sub.2 O(CH.sub.2).sub.q COOH, --CH.sub.2 O(CH.sub.2).sub.q OH, --CH.sub.2 O(CH.sub.2).sub.q CH.sub.2 OH, --CH.sub.2 O(CH.sub.2).sub.q (CH.sub.2).sub.r CH.sub.3, or --CH.sub.2 O(CH.sub.2 O).sub.q -Aryl,
- wherein said compound is other than the compounds sialyl-Lewis-X and -A and their derivatives, which derivatives, instead of an N-acetyl group, carry the substituents N.sub.3, NH.sub.2 or OH or which derivatives, instead of fucose, carry glycerol.
A compound of formula I ##STR32## in which R.sup.1 and R.sup.2 independently of one another together form a six-membered carbo- or heterocycle which is either unsubstituted or has at least one substituent selected from the group consisting of R.sup.7, R.sup.8 and R.sup.9,
- R.sup.3 and R.sup.6 together form a six-membered carbo- or hetero-cycle having at least one substituent X.sup.4,
- R.sup.4 and R.sup.5 independently of one another are H, OH, O(CR.sup.10 R.sup.11).sub.n COOH, OCX.sup.3.sub.2 (CR.sup.10 R.sup.11).sub.n COOH, or OSO.sub.3 H,
- Y is O-.alpha.-NANA or O-.beta.-NANA,
- Z is a pyranose, a furanose or an open-chain polyalcohol,
- m, n, and q independently of one another are integers from 1 to 20,
- R.sup.7, R.sup.8, R.sup.9, and X.sup.4 independently of one another are --NH.sub.2, --COOH, --CH.sub.2 OH, --CH.sub.2 NH, --(CH.sub.2).sub.r CH.sub.3, aryl, --CH.sub.2 O(CH.sub.2).sub.q H, --CH.sub.2 O(CH.sub.2).sub.q NH.sub.2, --CH.sub.2 O(CH.sub.2).sub.q COOH, --CH.sub.2 O(CH.sub.2).sub.q OH, --CH.sub.2 O(CH.sub.2).sub.q CH.sub.2 OH, --CH.sub.2 O(CH.sub.2).sub.q C.sub.1 -C.sub.25 -Alkyl, or --CH.sub.2 O(CH.sub.2).sub.q -Aryl, where r is 0 to 24,
- X.sup.3 is H, --(CH.sub.2).sub.r CH.sub.3, or aryl or alternatively
- X.sup.3.sub.2 is .dbd.O or .dbd.S and
- R.sup.10 and R.sup.11 independently of one another are X or --CH.sub.2 X or together form a six-membered carbo- or heterocycle having at least one substituent X.sup.4,
- X is H, --NH.sub.2, --COOH, --OH, --CH.sub.2 OH, --CH.sub.2 NH, --(CH.sub.2).sub.r CH.sub.3, aryl, --CH.sub.2 O(CH.sub.2).sub.q H, --CH.sub.2 O(CH.sub.2).sub.q NH.sub.2, --CH.sub.2 O(CH.sub.2).sub.q COOH, --CH.sub.2 O(CH.sub.2).sub.q OH, --CH.sub.2 O(CH.sub.2).sub.q CH.sub.2 OH, --CH.sub.2 O(CH.sub.2).sub.q C.sub.1 -C.sub.25 -Alkyl, or --CH.sub.2 O(CH.sub.2).sub.q -Aryl, where r is 0 to 24,
- wherein said compound is other than the compounds sialyl-Lewis-X and -A and their derivatives, which derivatives, instead of an N-acetyl group, carry the substituents N.sub.3, NH.sub.2 or OH or which derivatives, instead of fucose, carry glycerol.
A compound of formula I ##STR33## in which R.sup.1 and R.sup.2 independently of one another are H, CH.sub.2 X or CH.sub.2 O(CH.sub.2).sub.m X.sup.1, wherein X and X.sup.1 independently of one another are H, --NH.sub.2, --COOH, --OH, --CH.sub.2 OH, --CH.sub.2 NH, --(CH.sub.2).sub.r CH.sub.3, aryl or --CH.sub.2 O(CH.sub.2).sub.q H, --CH.sub.2 O(CH.sub.2).sub.q NH.sub.2, --CH.sub.2 O(CH.sub.2).sub.q COOH, --CH.sub.2 O(CH.sub.2).sub.q OH, --CH.sub.2 O(CH.sub.2).sub.q CH.sub.2 OH, --CH.sub.2 O(CH.sub.2).sub.q (CH.sub.2).sub.r CH.sub.3, or --CH.sub.2 O(CH.sub.2).sub.q -Aryl, where r is 0 to 24, or together form a six-membered carbocycle which is either unsubstituted or has at least one substituent selected from the group consisting of R.sup.7, R.sup.8 and R.sup.9,
- R.sup.3 and R.sup.6 together form a six-membered carbo- or heterocycle having at least one substituent X.sup.4,
- R.sup.4 and R.sup.5 independently of one another are H, OH, CH.sub.2 OH, O(CR.sup.10 R.sup.11).sub.n COOH, OCX.sup.3.sub.2 (CR.sup.10 R.sup.11).sub.n COOH, or OSO.sub.3 H,
- Y is O-.alpha.-NANA, O-.beta.-NANA, or --O--CH.sub.2 --COOH,
- Z is a pyranose or a furanose,
- m, n, and q independently of one another are integers from 1 to 20,
- R.sup.7, R.sup.8, R.sup.9, and X.sup.4 independently of one another are --NH.sub.2, --COOH, --CH.sub.2 OH, --CH.sub.2 NH, --(CH.sub.2).sub.r CH.sub.3, aryl, --CH.sub.2 O(CH.sub.2).sub.q H, --CH.sub.2 O(CH.sub.2).sub.q NH.sub.2, --CH.sub.2 O(CH.sub.2).sub.q COOH, --CH.sub.2 O(CH.sub.2).sub.q OH, --CH.sub.2 O(CH.sub.2).sub.q CH.sub.2 OH, --CH.sub.2 O(CH.sub.2).sub.q (CH.sub.2).sub.r CH.sub.3, or --CH.sub.2 O(CH.sub.2).sub.q -Aryl, where r is 0 to 24,
- X.sup.3 is --(CH.sub.2).sub.r CH.sub.3, or aryl, or alternatively
- X.sup.3.sub.2 is .dbd.O or .dbd.S, and
- R.sup.10 and R.sup.11 independently of one another are X or --CH.sub.2 X or together form a six-membered carbo- or heterocycle having at least one substituent X.sup.4,
- wherein said compound is other than the compounds sialyl-Lewis-X and -A and their derivatives, which derivatives, instead of an N-acetyl group, carry the substituents N.sub.3, NH.sub.2 or OH or which derivatives, instead of fucose, carry glycerol.
Dependencies are inferred from the claim text.