Synthesis and anticonvulsant and sedative-hypnotic activity of 4-(alkylimino)-2,3-dihydro-4H-1-benzopyrans and -benzothiopyrans

J Med Chem. 1990 Oct;33(10):2865-9. doi: 10.1021/jm00172a030.

Abstract

A series of 4-(alkylimino)-5-hydroxy-7-alkyl-2,3-dihydro-4H-1-benzopyrans and -thiopyrans were synthesized and evaluated for anticonvulsant activity. Preliminary screening of these compounds revealed that 2,2-dimethyl-4-[(2-hydroxyalkyl)imino]-5-hydroxy-7-pentyl-2,3- dihydro-4H-1-benzopyrans 19 and 29, the 7-butyl analogue 34, and the corresponding 7-pentyl-4H-1-benzothiopyrans 38 and 39 had the most promising anticonvulsant activity. Synthesis of both enantiomers of 29 and 39 indicated that the R isomers 30 and 40 were the most active and showed very good protection against MES, pentylenetetrazole, and mercaptopropionic acid induced seizures after oral administration in mice. In the Irwin test these compounds showed a generalized depressant activity but at dosages higher than those showing anticonvulsant activity, whereas acute toxicity after oral administration was low (LD50 higher than 400 mg/kg).

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis*
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / pharmacology
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromans / chemical synthesis
  • Chromans / chemistry
  • Chromans / pharmacology
  • Dose-Response Relationship, Drug
  • Hypnotics and Sedatives / chemical synthesis*
  • Mice
  • Pentylenetetrazole / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Anticonvulsants
  • Benzopyrans
  • Chromans
  • Hypnotics and Sedatives
  • FCE 23819
  • Pentylenetetrazole