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PAF inhibitory activity of diketopiperazines: Structure‐activity relationships
Author(s) -
Shimazaki Norihiko,
Shima Ichiro,
Okamoto Masanori,
Yoshida Keizo,
Hemmi Keiji,
Hashimoto Masashi
Publication year - 1991
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536526
Subject(s) - diketopiperazines , lipidology , inhibitory postsynaptic potential , chemistry , neurochemistry , clinical chemistry , structure–activity relationship , stereochemistry , biochemistry , psychology , neuroscience , in vitro , neurology
FR900452, a natural product isolated from the culture broth of Streptomyces phaeofaciens No. 7739, was found to inhibit PAF‐induced rabbit platelet aggregation with an IC 50 of 3.7×10 −7 M. FR900452, 1‐methyl‐3‐[1‐[5‐methylthiomethyl‐6‐oxo‐3‐(2‐oxo‐3‐cyclopenten‐1‐ylidene)‐2‐piperazinyl]ethyl]‐2‐indoline, has an oxocylopentylidene group incorporated as a vinylogous amide in a diketopiperazine skeleton. This unique structure led us to synthesize diketopiperazine derivatives, 3‐arylalkyl‐6‐substituted‐piperazine‐2,5‐diones. their observed PAF inhibitory activity suggest that the D‐D configuration of diketopiperazine is an important factor for anti‐PAF activity and that the hydrophobic aromatic portion may play a specific role in the binding of the diketopiperazine to the PAF receptor.