Premium
Synthesis and Evaluation of a Novel Series of Pyrrolizine Derivatives as Dual Cyclooxygenase‐1 and 5‐Lipoxygenase Inhibitors
Author(s) -
Laufer Stefan,
Striegel HansGünter,
Neher Karola,
Zechmeister Pia,
Donat Cornelia,
Stolingwa Katrin,
Baur Sibylle,
Tries Susanne,
Kammermeier Thomas,
Dannhardt Gerd,
Kiefer Werner
Publication year - 1997
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.19973300908
Subject(s) - cyclooxygenase , chemistry , arachidonate 5 lipoxygenase , platelet , lipoxygenase , context (archaeology) , whole blood , monoclonal antibody , substituent , enzyme , pharmacology , stereochemistry , biochemistry , antibody , immunology , medicine , arachidonic acid , biology , paleontology
Abstract The aim of our study was to investigate structure activity relationship following the replacement of the 6‐phenyl substituent at the 6,7‐diaryl‐2,3‐dihydropyrrolizine template by various heteroaromatic residues. In this context we developed a new, efficient, and highly sensitive test method for the screening of dual cyclooxygenase‐1 (COX‐1) and 5‐lipoxygenase (5‐LOX) inhibitors. We used human platelets as a source of COX‐1 and human PMNLs as a source of 5‐LOX. Both cell types were isolated from the same volume of blood. PGE 2 and LTB 4 respectively were determined by highly selective and sensitive ELISA kits, using monoclonal antibodies. For a single determination at most 0.5 mL whole blood is needed.