Method of using diketopiperazines and composition containing them
AssigneeDmi Biosciences, Inc.
InventorsDavid Bar-Or, C. Gerald Curtis, Nagaraja K. R. Rao, Greg Thomas
Life of this patent
Estimating the term…
Abstract
The invention provides a method of inhibiting the effects of platelet activating factor (PAF). For instance, a disease or condition mediated by PAF (particularly inflammation) can be treated or platelet aggregation can be inhibited. The invention also provides a method of inhibiting the production and/or release of interleukin 8 (IL-8) by cells. The effects of PAF and the production and/or release of IL-8 are inhibited according to the invention by a compound of the formula: wherein R1 and R2 are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.
Claims40
A method of treating a disease or condition mediated by platelet activating factor comprising administering to an animal in need thereof an effective amount of a compound of the formula:
- wherein:
- R1 is —CH2COR3, or —CH2CH2COR3;
- R2 is the side chain of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, phenylalanine, tyrosine, tryptophan, thyroxine, cysteine, methionine, norvaline and ornithine;
- R3 is —OH, —NH2, —OR4, —NHR4, or —NR4R4;
- and
- each R4 is independently an alkyl, aryl, alkylaryl, or arylalkyl;
- or
- a physiologically-acceptable salt thereof.
A method of inhibiting inflammation comprising administering to an animal in need thereof an effective amount of a compound of the formula:
- wherein:
- R1 is —CH2COR3, or —CH2CH2COR3;
- R2 is the side chain of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, phenylalanine, tyrosine, tryptophan, thyroxine, norvaline and ornithine;
- R3 is —OH, —NH2, —OR4, —NHR4, or —NR4R4;
- and
- each R4 is independently an alkyl, aryl, alkylaryl, or arylalkyl;
- or
- a physiologically-acceptable salt thereof.
A method of inhibiting aggregation of platelets comprising contacting the platelets with an effective amount of a compound of the formula:
- wherein:
- R1 is —CH2COR3, or —CH2CH2COR3;
- R2 is the side chain of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, phenylalanine, tyrosine, tryptophan, thyroxine, cysteine, methionine, norvaline and ornithine;
- R3 is —OH, —NH2, —OR4, —NHR4, or —NR4R4;
- and
- each R4 is independently an alkyl, aryl, alkylaryl, or arylalkyl;
- or
- a physiologically-acceptable salt thereof.
A method of inhibiting the production, release or both of interleukin 8 by cells comprising contacting the cells with an effective amount of a compound of the formula:
- wherein:
- R1 is —CH2COR3, or —CH2CH2COR3;
- R2 is the side chain of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, phenylalanine, tyrosine, tryptophan, thyroxine, cysteine, methionine, norvaline and ornithine;
- R3 is —OH, —NH2, —OR4, —NHR4, or —NR4R4;
- and
- each R4 is independently an alkyl, aryl, alkylaryl, or arylalkyl;
- or
- a physiologically-acceptable salt thereof.
A method of inhibiting the effects of platelet activating factor (PAF) comprising contacting the PAF with an effective amount of a compound of the formula:
- wherein:
- R1 is —CH2COR3, or —CH2CH2COR3;
- R2 is the side chain of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, phenylalanine, tyrosine, tryptophan, thyroxine, cysteine, methionine, norvaline and ornithine;
- R3 is —OH, —NH2, —OR4, —NHR4, or —NR4R4;
- and
- each R4 is independently an alkyl, aryl, alkylaryl, or arylalkyl;
- or
- a physiologically-acceptable salt thereof.
A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and an active ingredient having the formula:
- wherein:
- R1 is —CH2COR3, or —CH2CH2COR3;
- R2 is the side chain of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, hydroxylysine, histidine, arginine, phenylalanine, tyrosine, tryptophan, thyroxine, and norvaline;
- R3 is —OH, —NH2, —OR4, —NHR4, or —NR4R4;
- and
- each R4 is independently an alkyl, aryl, alkylaryl, or arylalkyl, or
- a physiologically-acceptable salt thereof.
Dependencies are inferred from the claim text.