US4816450A
Expired / Lapsed
US
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Inhibition of protein kinase C by long-chain bases
Assignee: Duke University
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Filing: 1986-09-15
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Granted: 1989-03-28
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Expires: 2006-09-15
Abstract
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 2 --CH 2 -- or --CH═CH--, which may be substituted by one or more halogens or C 1 -C 3 alkyl groups, wherein Y is ##STR2## wherein W is a halogen; wherein R 1 and R 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.
Inventors
- 👤 Robert M. Bell
- 👤 Carson Loomis
- 👤 Yusuf Hannun
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 02:04
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/66; A61K31/683; A61K31/685; A61P; A61P29/00; A61P35/00; A61P43/00; C; C07; C07H; C07H15/00; C07H15/02; C07H15/04; C07H15/10
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
143 words
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 3 --(CH 2 ) n -- or CH 3 --(CH 2 ) m --CH═CH--(CH 2 ) p -- wherein n is 2-30; m is 1-15 and p is 1-15; wherein X is --CH 2 --CH 2 -- or --CH═CH--, or such substituted by one or more halogens or C 1 -C 3 alkyl groups; wherein Y is ##STR11## wherein W is a halogen; wherein R 1 and R 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##
Claim 2
Independent Claim
143 words
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 3 --(CH 2 ) n -- or CH 3 --(CH 2 ) m --CH═CH--(CH 2 ) p -- wherein n is 2-30; m is 1-15 and p is 1-15; wherein X is --CH 2 --CH 2 -- or --CH═CH--, or such substituted by one or more halogens or C 1 -C 3 alkyl groups; wherein Y is ##STR11## wherein W is a halogen; wherein R 1 and R 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##
Claim 3
Dependent Claim
9 words
The method of claim 1, wherein Y is ##STR13##
Claim 4
Independent Claim
146 words
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 3 --(CH 2 ) n -- or CH 3 --(CH 2 ) m --CH═CH--(CH 2 ) p -- wherein n is 2-30; m is 1-15 and p is 1-15; wherein X is --CH 2 --CH 2 -- or --CH═CH--, or such substituted by one or more halogens or C 1 -C 3 alkyl groups; Wherein Y is ##STR15## wherein W is a halogen; wherein R 1 and R 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##
Claim 5
Independent Claim
146 words
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 3 --(CH 2 ) n -- or CH 3 --(CH 2 ) m --CH═CH--(CH 2 ) p -- wherein n is 2-30; m is 1-15 and p is 1-15; wherein X is --CH 2 --CH 2 -- or --CH═CH--, or such substituted by one or more halogens or C 1 -C 3 alkyl groups; Wherein Y is ##STR15## wherein W is a halogen; wherein R 1 and R 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##
Claim 6
Dependent Claim
9 words
The method of claim 3, wherein Y is ##STR17##
Claim 7
Dependent Claim
15 words
The method of claim 1, wherein said contacting occurs in vivo in a human being.
Claim 8
Dependent Claim
10 words
The method of claim 1, wherein said compound is sphingosine.
Claim 9
Dependent Claim
10 words
The method of claim 1, wherein said compound is sphinganine
Claim 10
Dependent Claim
10 words
The method of claim 1, wherein said compound is psychosine.
Claim 11
Independent Claim
146 words
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 3 --(CH 2 ) n -- or CH 3 --(CH 2 ) m --CH═CH--(CH 2 ) p -- wherein n is 2-30; m is 1-15 and p is 1-15; wherein X is --CH 2 --CH 2 -- or --CH═CH--, or such substituted by one or more halogens or C 1 -C 3 alkyl groups; wherein Y is ##STR19## wherein W is a halogen, wherein R 1 and R 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##
Claim 12
Independent Claim
146 words
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 3 --(CH 2 ) n -- or CH 3 --(CH 2 ) m --CH═CH--(CH 2 ) p -- wherein n is 2-30; m is 1-15 and p is 1-15; wherein X is --CH 2 --CH 2 -- or --CH═CH--, or such substituted by one or more halogens or C 1 -C 3 alkyl groups; wherein Y is ##STR19## wherein W is a halogen, wherein R 1 and R 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##
Claim 13
Dependent Claim
9 words
The method of claim 9, wherein Y is ##STR21##
Claim 14
Dependent Claim
55 words
A method for inhibiting protein kinase C, which comprises contacting a cell containing protein kinase C, with a pro-drug analogue of a protein kinase C inhibitor according to claim 1, wherein the nitrogen atom of said inhibitor is acylated with an in vivo enzyme cleavable C 1 -C 8 acyl group or an amino acid.
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