IAM retention and blood brain barrier penetration

A series of 1,3,5-triazines possessing bronchospasmolytic, antiinflammatory and central nervous system activities have been chromatographically characterized using commercially available immobilized artificial membrane (IAM) columns. The obtained capacity factors correlated well (r = 0.97) with the shake-flask octanol-buffer (log P) partition coefficient but less well (r = 0.72) with capacity factors obtained using RP-HPLC columns (log k'(w). Moreover it was shown that the potentiation of oxotremorine-induced tremors, observed for this class of compounds correlated well with both log P and log k'(IAM) parameters. On the contrary such a correlation did not exist when using Delta log P (log Poctanol-water-log Pcyclohexane-water). Thus the determination of log k'(IAM) is a fast, reliable and efficient method for assessing lipophilic behaviour of 1,3,5-triazines in connection with CNS-related biological activities. (C) Elsevier, Paris.