US2012202762A1PendingUtilityA1
Methods of use of glycomimetics with replacements for hexoses and n-acetyl hexosamines
Est. expiryFeb 9, 2027(~0.6 yrs left)· nominal 20-yr term from priority
Inventors:John L. Magnani
A61P 9/00A61P 3/10A61P 9/10A61P 7/06A61P 9/14A61P 37/06A61P 7/00A61P 37/02A61P 31/06A61P 29/00A61P 35/00A61P 17/00A61K 31/7032A61P 17/06A61P 17/04
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Claims
Abstract
Methods are provided for using a compound to treat, for example, endothelial dysfunction including vascular abnormalities. More specifically, methods are described for using an oligosaccharide compound or glycomimetic compound wherein a cyclohexane derivative is incorporated in either.
Claims
exact text as granted — not AI-modified1 . A method for treating an endothelial dysfunction comprising administering to an individual in need thereof in an amount effective to treat the endothelial dysfunction an oligosaccharide or glycomimetic compound that contains at least one cyclohexane derivative, wherein the cyclohexane derivative has the formula:
wherein,
R 1 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; C(═O)OX, alkanyl substituted with C(═O)OX, C(═O)NHX, alkanyl substituted with C(═O)NHX, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH;
R 2 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)OX where X is C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)NH(CH 2 ) n NH 2 where n=0-30, C(═O)NHX or CX 2 OH, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; with the proviso that R 1 and R 2 are not both H;
the cyclohexane derivative is at least attached to the oligosaccharide or glycomimetic compound at an OH, R 1 or R 2 .
2 . The method according to claim 1 wherein the compound comprises:
wherein,
R 1 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; C(═O)OX, alkanyl substituted with C(═O)OX, C(═O)NHX, alkanyl substituted with C(═O)NHX, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH;
R 2 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)OX where X is C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)NH(CH 2 )—NH 2 where n=0-30, C(═O)NHX or CX 2 OH, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; with the proviso that R 1 and R 2 are not both H;
R 3 =—OH,
—O—C(═O)—X, —NH 2 , —NH—C(═O)—NHX, or —NH—C(═O)—X where n=0-2 and X is independently selected from C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl,
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, and where n=0-10, and any of the above ring compounds may be substituted with one to three independently selected of Cl, F, CF 3 , C 1 -C 8 alkoxy, NO 2 , C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, C 1 -C 14 aryl, or OY, C(═O)OY, NY 2 or C(═O)NHY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, or C 1 -C 14 aryl;
R 4 =
6′ sulfated GlcNAc, 6′ carboxylated GlcNAc, 6′ sulfated GalNAc, 6′ sulfated galactose, 6′ carboxylated galactose,
where Q is H or a physiologically acceptable salt or C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) n -aryl or (CH 2 ) n -heteroaryl where n is 1-10, and where R 9 is aryl, heteroaryl, cyclohexane, t-butane, adamantane, or triazole, and any of R 9 may be substituted with one to three independently selected of Cl, F, CF 3 , C 1 -C 8 alkoxy, NO 2 , C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or OY, C(═O)OY, NY 2 or C(═O)NHY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or C 1 -C 14 aryl; or
where R 10 is one of
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, n=1-4, Z and Y═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl and heteroaryl substituted with Me, OMe, halide, OH; and
R 5 ═H, D-mannose, L-galactose, D-arabinose, L-fucose, polyols
where X═CF 3 , cyclopropyl or phenyl, or
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10,
and where R 11 is aryl, heteroaryl,
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, and where n=0-10, and any one of the above ring compounds may be substituted with one to three independently selected of Cl, F, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or OY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl or C 1 -C 8 alkynyl.
3 . The method according to claim 1 wherein the compound consists of the compound of claim 2 .
4 . The method according to claim 1 wherein the compound has the formula:
where Q is H or a physiologically acceptable salt, and Me is methyl.
5 . The method according to claim 1 wherein the compound has the formula:
where Q is H or a physiologically acceptable salt, Me is methyl and Bz is benzoyl.
6 . The method according to claim 1 wherein the compound has the formula:
where Q is H or a physiologically acceptable salt, Me is methyl and Bz is benzoyl.
7 . The method according to claim 1 wherein the compound has the formula:
where Q is H or a physiologically acceptable salt, Me is methyl and Bz is benzoyl.
8 . The method according to claim 1 wherein the compound has the formula:
where Q is H or a physiologically acceptable salt, and Me is methyl.
9 . The method according to claim 1 wherein the compound has the formula:
where Q is H or a physiologically acceptable salt, Me is methyl and Bz is benzoyl.
10 . The method according to claim 1 wherein the compound has the formula:
where Me is methyl.
11 . The method according to claim 1 wherein the compound has the formula:
where Q is H or a physiologically acceptable salt, Me is methyl and Bz is benzoyl.
12 . The method according to claim 1 wherein the compound has the formula:
where Q is H or a physiologically acceptable salt, and Me is methyl.
13 . The method according to claim 1 wherein the compound has the formula:
where Q is H or a physiologically acceptable salt, Me is methyl and Bz is benzoyl.
14 . The method according to claim 1 wherein the compound has the formula:
where Q is H or a physiologically acceptable salt, and Me is methyl.
15 . The method according to claim 1 wherein the compound has the formula:
where Q is H or a physiologically acceptable salt, Me is methyl and Bz is benzoyl.
16 . The method according to claim 1 wherein the compound has the formula:
where Me is methyl, Et is ethyl and Bz is benzoyl.
17 . The method according to claim 1 wherein the compound has the formula:
where Me is methyl and Bz is benzoyl.
18 . The method according to claim 1 wherein the compound has the formula:
where Me is methyl, Et is ethyl and Bz is benzoyl.
19 . The method according to claim 1 wherein the compound has the formula:
where Me is methyl and Bz is benzoyl.
20 . The method according to claim 1 wherein the compound has a polyethylene glycol attached thereto.
21 . The method according to claim 1 wherein the compound is attached by polyethylene glycol to another of the compound.
22 . The method according to claim 1 wherein the endothelial dysfunction is a vascular abnormality.
23 . The method according to claim 22 wherein the vascular abnormality is associated with diabetes.
24 . The method according to claim 22 wherein the vascular abnormality is associated with sickle cell disease.
25 . The method according to claim 22 wherein the vascular abnormality is associated with atherosclerosis.
26 . The method according to claim 25 wherein the individual is also being treated with aspirin or an aspirin substitute useful for atherosclerosis.
27 . A method for treating graft vs. host disease comprising administering to an individual in need thereof in an amount effective to treat graft vs. host disease an oligosaccharide or glycomimetic compound that contains at least one cyclohexane derivative wherein the cyclohexane derivative has the formula:
wherein,
R 1 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; C(═O)OX, alkanyl substituted with C(═O)OX, C(═O)NHX, alkanyl substituted with C(═O)NHX, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH;
R 2 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)OX where X is C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)NH(CH 2 ) n NH 2 where n=0-30, C(═O)NHX or CX 2 OH, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; with the proviso that R 1 and R 2 are not both H;
the cyclohexane derivative is at least attached to the oligosaccharide or glycomimetic compound at an OH, R 1 or R 2 .
28 . The method according to claim 27 wherein the compound comprises:
wherein,
R 1 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; C(═O)OX, alkanyl substituted with C(═O)OX, C(═O)NHX, alkanyl substituted with C(═O)NHX, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH;
R 2 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)OX where X is C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)NH(CH 2 )—NH 2 where n=0-30, C(═O)NHX or CX 2 OH, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; with the proviso that R 1 and R 2 are not both H;
—O—C(═O)—X, —NH 2 , —NH—C(═O)—NHX, or —NH—C(═O)—X where n=0-2 and X is independently selected from C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl,
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, and where n=0-10, and any of the above ring compounds may be substituted with one to three independently selected of Cl, F, CF 3 , C 1 -C 8 alkoxy, NO 2 , C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, C 1 -C 14 aryl, or OY, C(═O)OY, NY 2 or C(═O)NHY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, or C 1 -C 14 aryl;
6′ sulfated GlcNAc, 6′ carboxylated GlcNAc, 6′ sulfated GalNAc, 6′ sulfated galactose, 6′ carboxylated galactose,
where Q is H or a physiologically acceptable salt or C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) n -aryl or (CH 2 ) n -heteroaryl where n is 1-10, and where R 9 is aryl, heteroaryl, cyclohexane, t-butane, adamantane, or triazole, and any of R 9 may be substituted with one to three independently selected of Cl, F, CF 3 , C 1 -C 8 alkoxy, NO 2 , C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or OY, C(═O)OY, NY 2 or C(═O)NHY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or C 1 -C 14 aryl; or
where R 10 is one of
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, n=1-4, Z and Y═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl and heteroaryl substituted with Me, OMe, halide, OH; and
R 5 ═H, D-mannose, L-galactose, D-arabinose, L-fucose, polyols
where X═CF 3 , cyclopropyl or phenyl, or
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10,
and where R 11 is aryl, heteroaryl,
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, and where n=0-10, and any one of the above ring compounds may be substituted with one to three independently selected of Cl, F, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or OY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl or C 1 -C 8 alkynyl.
29 . The method according to claim 27 wherein the compound consists of the compound of claim 28 .
30 . A method for treating cutaneous T-cell lymphoma comprising administering to an individual in need thereof in an amount effective to treat cutaneous T-cell lymphoma an oligosaccharide or glycomimetic compound that contains at least one cyclohexane derivative wherein the cyclohexane derivative has the formula:
wherein,
R 1 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; C(═O)OX, alkanyl substituted with C(═O)OX, C(═O)NHX, alkanyl substituted with C(═O)NHX, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH;
R 2 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)OX where X is C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)NH(CH 2 ) n NH 2 where n=0-30, C(═O)NHX or CX 2 OH, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; with the proviso that R 1 and R 2 are not both H;
the cyclohexane derivative is at least attached to the oligosaccharide or glycomimetic compound at an OH, R 1 or R 2 .
31 . The method according to claim 30 wherein the compound comprises:
wherein,
R 1 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; C(═O)OX, alkanyl substituted with C(═O)OX, C(═O)NHX, alkanyl substituted with C(═O)NHX, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH;
R 2 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)OX where X is C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)NH(CH 2 ) n NH 2 where n=0-30, C(═O)NHX or CX 2 OH, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; with the proviso that R 1 and R 2 are not both H;
—O—C(═O)—X, —NH 2 , —NH—C(═O)—NHX, or —NH—C(═O)—X where n=0-2 and X is independently selected from C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl,
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, and where n=0-10, and any of the above ring compounds may be substituted with one to three independently selected of Cl, F, CF 3 , C 1 -C 8 alkoxy, NO 2 , C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, C 1 -C 14 aryl, or OY, C(═O)OY, NY 2 or C(═O)NHY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, or C 1 -C 14 aryl;
6′ sulfated GlcNAc, 6′ carboxylated GlcNAc, 6′ sulfated GalNAc, 6′ sulfated galactose, 6′ carboxylated galactose,
where Q is H or a physiologically acceptable salt or C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) n -aryl or (CH 2 ) n -heteroaryl where n is 1-10, and where R 9 is aryl, heteroaryl, cyclohexane, t-butane, adamantane, or triazole, and any of R 9 may be substituted with one to three independently selected of Cl, F, CF 3 , C 1 -C 8 alkoxy, NO 2 , C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or OY, C(═O)OY, NY 2 or C(═O)NHY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or C 1 -C 14 aryl; or
where R 10 is one of
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, n=1-4, Z and Y═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl and heteroaryl substituted with Me, OMe, halide, OH; and
R 5 ═H, D-mannose, L-galactose, D-arabinose, L-fucose, polyols
where X═CF 3 , cyclopropyl or phenyl, or
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkaanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10,
and where R 11 is aryl, heteroaryl,
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, and where n=0-10, and any one of the above ring compounds may be substituted with one to three independently selected of Cl, F, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or OY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl or C 1 -C 8 alkynyl.
32 . The method according to claim 30 wherein the compound consists of the compound of claim 31 .
33 . A method for treating disease involving inflammatory cells in the skin comprising administering to an individual in need thereof in an amount effective to treat disease involving inflammatory cells in the skin an oligosaccharide or glycomimetic compound that contains at least one cyclohexane derivative wherein the cyclohexane derivative has the formula:
wherein,
R 1 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; C(═O)OX, alkanyl substituted with C(═O)OX, C(═O)NHX, alkanyl substituted with C(═O)NHX, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH;
R 2 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)OX where X is C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)NH(CH 2 ) n NH 2 where n=0-30, C(═O)NHX or CX 2 OH, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; with the proviso that R 1 and R 2 are not both H;
the cyclohexane derivative is at least attached to the oligosaccharide or glycomimetic compound at an OH, R 1 or R 2 .
34 . The method according to claim 33 wherein the compound comprises:
wherein,
R 1 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; C(═O)OX, alkanyl substituted with C(═O)OX, C(═O)NHX, alkanyl substituted with C(═O)NHX, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH;
R 2 ═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, OH, or NHX where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)OX where X is C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; —C(═O)NH(CH 2 ) n NH 2 where n=0-30, C(═O)NHX or CX 2 OH, where X═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; O(═O)X, OX, NHX, NH(═O)X, where X═H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl or heteroaryl either of which may be substituted with one or more of Me, OMe, halide, or OH; with the proviso that R 1 and R 2 are not both H;
R 3 =—OH,
—O—C(═O)—X, —NH 2 , —NH—C(═O)—NHX, or —NH—C(═O)—X where n=0-2 and X is independently selected from C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl,
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, and where n=0-10, and any of the above ring compounds may be substituted with one to three independently selected of Cl, F, CF 3 , C 1 -C 8 alkoxy, NO 2 , C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, C 1 -C 14 aryl, or OY, C(═O)OY, NY 2 or C(═O)NHY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, or C 1 -C 14 aryl;
R 4 =
6′ sulfated GlcNAc, 6′ carboxylated GlcNAc, 6′ sulfated GalNAc, 6′ sulfated galactose, 6′ carboxylated galactose,
where Q is H or a physiologically acceptable salt or C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) n -aryl or (CH 2 ) n -heteroaryl where n is 1-10, and where R 9 is aryl, heteroaryl, cyclohexane, t-butane, adamantane, or triazole, and any of R 9 may be substituted with one to three independently selected of Cl, F, CF 3 , C 1 -C 8 alkoxy, NO 2 , C 1 -C 3 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or OY, C(═O)OY, NY 2 or C(═O)NHY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or C 1 -C 14 aryl; or
where R 10 is one of
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, n=1-4, Z and Y═C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, halogenated C 1 -C 8 alkanyl, aryl and heteroaryl substituted with Me, OMe, halide, OH; and
R 5 ═H, D-mannose, L-galactose, D-arabinose, L-fucose, polyols
where X═CF 3 , cyclopropyl or phenyl, or
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10,
and where R 11 is aryl, heteroaryl,
where Q is H or a physiologically acceptable salt, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl, aryl, heteroaryl, (CH 2 ) m -aryl or (CH 2 ) m -heteroaryl where m is 1-10, and where n=0-10, and any one of the above ring compounds may be substituted with one to three independently selected of Cl, F, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl, C 1 -C 8 alkynyl or OY where Y is H, C 1 -C 8 alkanyl, C 1 -C 8 alkenyl or C 1 -C 8 alkynyl.
35 . The method according to claim 33 wherein the compound consists of the compound of claim 34 .
36 . The method according to any one of claims 33 - 35 wherein the disease is dermatitis.
37 . The method according to any one of claims 33 - 35 wherein the disease is chronic eczema.
38 . The method according to any one of claims 33 - 35 wherein the disease is psoriasis.Cited by (0)
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