Anti-inflammatory planar chiral [2.2]paracyclophaneacetic acid enantiomers. 
To elucidate if the planar chiral paracyclophane moiety conveys pharmacological activity to arylacetic acid analogs in two animal models.  Female NMRI mice (6 mice/group); female Wistar rats (8 rats/group); thrombocytes from human blood.  The enantiomers of [2.2]paracyclophaneacetic acid were applied locally (10(-7) and 10(-6) mol/ear) and orally (10-100 mg/kg). ( a) Phorbol myristyl acetate model of acute inflammation of the inner auricle. ( b) Oxazolone model of allergic contact dermatitis. ( c) Carrageenan model of acute inflammation. ( d) Inhibition of cyclooxygenase-1 and 12-lipoxygenase (in vitro). ( a) PMA model: pR-(-)-[2.2]paracyclophaneacetic acid (10(-6) mmol/ear): 58% inhibition after 24 h (p < 0.05). ( b) Oxazolone model: pR-(-)-[2.2]paracyclophaneacetic acid (10(-6) mmol/ear): 42% inhibition after 24 h (p < 0.05). ( c) Carrageenan model: pR-(-)-[2.2]paracyclophaneacetic acid (10 mg/kg): 31.4% inhibition (paw volume 0.48 +/- 0.13 ml). ( d) Cyclooxygenase-1 and 12-lipoxygenase: no inhibition at concentrations up to 10 microM. The easily accessible [2.2]paracyclophane moiety should find its use in medicinal chemistry as it is a pharmacophoric substituent with the interesting feature of planar chirality.