Analogues of platelet activating factor. 5. Multiple oxygen substitution of the alkoxy chain

Racemic analogues of platelet activating factor (PAF) in which the alkoxy chain (R = -O(CH2)15CH3) has been replaced with a chain containing multiple ether linkages near the end (17, R = -O(CH2)8O(CH2)2O(CH2)2OCH3) or at the beginning (18, R = -O(CH2)2O(CH2)2O(CH2)9CH3) of the chain have been prepared. Both compounds exhibit reduced hypotensive and platelet aggregation responses compared to racemic C16-PAF (1a). This reduction in the biological activities is more apparent when the new oxygen atoms are located near the end of the chain. This substitution of additional oxygen atoms into the alkoxy chain does not result in any dramatic gains in selectivity of the biological responses.