Premium
Structure‐Activity Relationship Studies of 1‐Substituted 3‐Dodecanoylindole‐2‐carboxylic Acids as Inhibitors of Cytosolic Phospholipase A 2 ‐Mediated Arachidonic Acid Release in Intact Platelets
Author(s) -
Griessbach Klaus,
Klimt Monika,
Schulze Elfringhoff Alwine,
Lehr Matthias
Publication year - 2003
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200290008
Subject(s) - carboxylic acid , chemistry , arachidonic acid , phospholipase a2 , indole test , stereochemistry , moiety , cytosol , structure–activity relationship , platelet , biochemistry , enzyme , in vitro , biology , immunology
A series of 3‐dodecanoylindole‐2‐carboxylic acid derivatives with varied carboxylic acid substituents at the indole 1‐position were synthesized and evaluated for their ability to inhibit arachidonic acid release in human platelets mediated by the cytosolic phospholipase A 2 . Structure‐activity relationship studies revealed that increasing the polarity of these substituents by the introduction of additional polar groups in the proximity of the carboxylic acid moiety reduced activity. Conformational restriction of the indole‐1‐carboxylic acid substituents in distinct positions as well as extending the length of these residues led to compounds which did not substantially differ in their potencies.