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A series of selected analogues of 2-(3-ethoxyphenyl)-5,6-dihydro-s-triazole [5, 1-a] isoquinoline (DL 204-IT) modified at the three sites of metabolism of the DL 204-IT molecule, were studied for their anti-fertility activity and absorption (in situ and in vivo) following oral administration to the hamster. All test-compounds were rather well absorbed, nevertheless, the ratios between the oral and subcutaneous pregnancy termination activity ranged between 3 and 722, suggesting a marked influence of metabolic first-pass. One of these new anti-fertility agents, 2-(1, 1'-biphenyl-4-yl)-s-triazole [5, 1-a]-isoquinoline (L 14105), showed an interesting oral activity (ED50: 0.2 mg/kg/d), 300 times greater than that of the parent compound DL 204-IT.

Increased oral activity of a new class of non-hormonal pregnancy terminating agents.