Thienylpyrazoloquinolines: Potent Agonists and Inverse Agonists to Benzodiazepine Receptors

Article abstract of DOI:10.1021/jm00117a012

Synthesis and structure-activity relationships of a series of 2-(thien-3-yl)-and 2-(thien-2-yl)-2,5-dihydro-3H-pyrazolo<4,3-c>quinolin-3-ones are reported.A number of the compounds possessed 1 order of magnitude higher affinity for the receptors than diazepam.Planarity was one of the structural requirements for binding to benzodiazepine receptors.The activities of agonists and inverse agonists were assessed on the basis of inhibition or facilitation of the pentylenetetrazole-induced convulsions, respectively.Thien-3-yl compounds exhibited inverse agonist activity whereas thien-2-yl analogues with a 5'-alkyl group showed agonist activity.Substitution on the quinoline moiety did not enhance in vivo activity.The most potent compounds were the 5-methylthien-3-yl drivative 6a as an inverse agonist and the 5-methylthien-2yl compound 13 a as an agonist.