Increased oral activity of a new class of non-hormonal pregnancy terminating agents.
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.
D000019:Abortifacient Agents / Q000008:administration & dosage*; D000020:Abortifacient Agents, Nonsteroidal / Q000008:administration & dosage* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D006224:Cricetinae; D005260:Female; D007279:Injections, Subcutaneous; D007408:Intestinal Absorption; D007546:Isoquinolines / Q000008:administration & dosage* / Q000378:metabolism; D007700:Kinetics; D008647:Mesocricetus; D011247:Pregnancy
D000019:Abortifacient Agents; D000020:Abortifacient Agents, Nonsteroidal; D007546:Isoquinolines; C014924:L 11204