Inhibition of protein kinase C by long-chain bases
AssigneeDuke University
InventorsRobert M. Bell, Carson Loomis, Yusuf Hannun
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Abstract
Compositions for inhibiting protein kinase C, comprising an inhibitory amount of a compound having the formula: ##STR1## wherein Q is a hydrophobic group; wherein X is --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, which may be substituted by one or more halogens or C.sub.1 -C.sub.3 alkyl groups, wherein Y is ##STR2## wherein W is a halogen; wherein R.sub.1 and R.sub.2 may be the same or different and are selected from hydrogen, lower alkyl groups having from 1 to 7 carbon atoms, aralkyl, and aryl groups, and wherein Z is a phosphate or an organic group, and a pharmaceutically acceptable carrier material; and a method for inhibiting protein kinase C using such compositions.
Claims11
A method of inhibiting protein kinase C, which comprises contacting protein kinase C with an inhibitory amount of a compound having the formula:
- ##STR10## wherein Q is CH.sub.3 --(CH.sub.2).sub.n -- or CH.sub.3 --(CH.sub.2).sub.m --CH.dbd.CH--(CH.sub.2).sub.p -- wherein n is 2-30;
- m is 1-15 and p is 1-15;
- wherein X is --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, or such substituted by one or more halogens or C.sub.1 -C.sub.3 alkyl groups;
- wherein Y is ##STR11## wherein W is a halogen;
- wherein R.sub.1 and R.sub.2 are the same or different and are selected from hydrogen, lower alkyl groups having from 1 to 7 carbon atoms, aralkyl, and aryl groups, and
- wherein Z is selected from the group consisting of phosphate, H, galactosyl, sulfogalactosyl, glucosyl, lactosyl, trihexosyl, phosphorylcholine, GalNAc-Gal-Glc, Gal-GAl-Glc, Sia-Gal-Glc, ##STR12##
A method of inhibiting an oxidative burst in neutrophils, which comprises contacting a neutrophil with a protein kinase C inhibitory concentration of a compound having the formula:
- ##STR14## wherein Q is CH.sub.3 --(CH.sub.2).sub.n -- or CH.sub.3 --(CH.sub.2).sub.m --CH.dbd.CH--(CH.sub.2).sub.p -- wherein n is 2-30;
- m is 1-15 and p is 1-15;
- wherein X is --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, or such substituted by one or more halogens or C.sub.1 -C.sub.3 alkyl groups;
- Wherein Y is ##STR15## wherein W is a halogen;
- wherein R.sub.1 and R.sub.2 are the same or different and are selected from hydrogen, lower alkyl groups having from 1 to 7 carbons, aralkyl, and aryl groups, and
- wherein Z is selected from the group consisting of phosphate, H, galactosyl, sulfogalactosyl, glucosyl, lactosyl, trihexosyl, phosphorylcholine, GalNAc-Gal-Glc, Gal-Gal-Glc, Sia-Gal-Glc, ##STR16##
A method for treating inflammation, which comprises administering to a mammal suffering from inflammation a protein kinase C inhibitory concentration of a compound having the formula:
- ##STR18## wherein Q is CH.sub.3 --(CH.sub.2).sub.n -- or CH.sub.3 --(CH.sub.2).sub.m --CH.dbd.CH--(CH.sub.2).sub.p -- wherein n is 2-30;
- m is 1-15 and p is 1-15;
- wherein X is --CH.sub.2 --CH.sub.2 -- or --CH.dbd.CH--, or such substituted by one or more halogens or C.sub.1 -C.sub.3 alkyl groups;
- wherein Y is ##STR19## wherein W is a halogen, wherein R.sub.1 and R.sub.2 are the same or different and are selected from hydrogen, lower alkyl groups having from 1 to 7 carbon atoms, aralkyl, and aryl groups, and
- wherein Z is selected from the group consisting of phosphate, H, galactosyl, sulfogalactosyl, glucosyl, lactosyl, trihexosyl, phosphorylcholine, GalNAc-Gal-Glc, Gal-Gal-Glc, Sia-Gal-Glc, ##STR20##
Dependencies are inferred from the claim text.