Method of using diketopiperazines and composition containing them
View Patent ↗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 R 1 and R 2 are defined in the application, or a physiologically-acceptable salt thereof. The invention also provides pharmaceutical compositions comprising these compounds.
1. A pharmaceutical composition formulated as a sterile powder for reconstitution for parenteral administration comprising a pharmaceutically-acceptable carrier and a therapeutically effective dose of a diketopiperazine having the formula:
wherein:
R 1 is —CH 2 COR 3 , or —CH 2 CH 2 COR 3 ;
R 2 is the side chain of an amino acid selected from the group consisting of alanine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, hydroxylysine,;
R 3 is —OH, —NH 2 , —OR 4 , —NHR 4 , or —NR 4 R 4 ; and
each R 4 is independently an alkyl, aryl, alkylaryl, or arylalkyl, or
a physiologically-acceptable salt thereof
wherein the pharmaceutically-acceptable carrier comprises an excipient selected from the group consisting of an antioxidant, a buffer, a solute which will render the formulation isotonic with the blood of a mammalian recipient, a suspending agent, and a thickening agent.
2. The composition of claim 1 wherein R 2 is the side chain of alanine.
3. The composition of claim 1 wherein R 2 is the side chain of threonine.
4. The composition of claim 1 wherein R 2 is the side chain of aspartic acid, asparagine, glutamic acid or glutamine.
5. The composition of claim 1 wherein R 3 is —NH 2 and R 1 is —CH 2 CONH 2 .
6. The composition of claim 2 wherein R 3 is —NH 2 and R 1 is —CH 2 CONH 2 .