PAF receptor and "Cache-oreilles" effect. Simple PAF antagonists.
Nine simple and structurally flexible PAF antagonists were synthesized and their inhibitory effects on PAF induced platelet aggregation were measured. Compounds with PAF antagonistic activity exhibited a negative electrostatic potential generated by two trimethoxyphenyl groups (isocontour at -10 Kcal/mole) at various distances between the negative clouds. The optimal distance between the atoms generating the "cache-oreilles" system for exhibiting potent PAF antagonistic activity is estimated to be 11-13 A. In the flexible molecules studied, the dispersion of the electronic distribution is not necessarily favorable for anti-PAF activity. The data support the simple bipolarized model for the PAF receptor that has been proposed by the authors.
Lamotte-Brasseur
J
J
Centre d'Ingéniérie des Protéines, Institut de Chimie, Liége-Sart-Tilman, Belgium.
Heymans
F
F
Dive
G
G
Lamouri
A
A
Batt
J P
JP
Redeuilh
C
C
Hosford
D
D
Braquet
P
P
Godfroid
J J
JJ
D000818:Animals; D002151:Calorimetry; D015195:Drug Design; D004563:Electrochemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D043562:Receptors, G-Protein-Coupled
D007202:Indicators and Reagents; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor