Oral Hypoglycemic Agents. Pyrimidoindoles and Related Compounds

Article abstract of DOI:10.1021/jm00085a001

A series of pyrimido<1,2-a>indoles were synthesized and studied for their hypoglycemic activity following oral administration at standard dose of 100 mg/kg to fed rats.The effect of 10-alkoxyalkyl, 10-alkyl, 10-aryl, and 3,3-dialkyl substitution on the activity of 10-hydroxypyrimido<1,2-a>indoles was investigated.Relative potencies of a number of the most active compounds were defined by three-point dose-response studies.The most potent compounds were those with either 3,3-dimethyl substituents, compounds 21, 22, and 38, or 3,3-spirocyclohexane substituents, compounds 39 and 49. 10-Aminopyrimido<1,2-a>indoles were in general less active than the 10-hydroxy analogues, and potency was further decreased by derivatizing the 10-amino group.The most potent 10-amino derivatives were 57 and 58.