Structure-Activity Relationships in Pyrrolo[1,2-c]Thiazoles PAF Receptor Antagonists

Involvement of platelet activating factor (PAF) in various pathological conditions prompted many research teams, soon after its identification in 1979, to look for products blocking the effects of this potent biological mediator. The principal chemical approach was the synthesis of PAF-related derivatives such as CV 3988, which was the first published PAF antagonist. However, PAF antagonist activity was also reported for natural products such as kadsurenone. Nonlipid synthetic compounds with PAF receptor antagonist properties were unknown until the synthesis of RP 48740 which was the first member of the potent pyrrolo[1,2-c]thiazole family of PAF receptor antagonists. Introduction of additional substituents on the aromatic ring of RP 52629 or of RP 52770 does not improve the PAF receptor antagonist activity. Accordingly, the high activity of RP 59227 in antagonizing the PAF-evoked effects suggests that this compound may be of great interest in treating the pathological manifestations where PAF may be involved.