title: Oral hypoglycemic agents. Pyrimido[1,2-a]indoles and related compounds.
abstract: A series of pyrimido[1,2-a]indoles were synthesized and studied for their hypoglycemic activity following oral administration at a 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.
authors.affiliation: Department of Medicinal Chemistry, Wyeth Research, Maidenhead, Berkshire, England.
authors.forename: I A
authors.initials: IA
authors.lastname: Cliffe
authors.forename: E L
authors.initials: EL
authors.lastname: Lien
authors.forename: H L
authors.initials: HL
authors.lastname: Mansell
authors.forename: K E
authors.initials: KE
authors.lastname: Steiner
authors.forename: R S
authors.initials: RS
authors.lastname: Todd
authors.forename: A C
authors.initials: AC
authors.lastname: White
authors.forename: R M
authors.initials: RM
authors.lastname: Black
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007211:Indoles; D011743:Pyrimidines; C009990:ciclazindol