ANXIOLYTIC ACTIVITY OF ANALOGS OF -BENZYLAMINO-2-METHYL-7H-PYRROLO[2,3-D]PYRIMIDINES

An extensive series of analogues of the lead anxiolytic 4-benzylamino- 2-methylpyrrolo[2,3-d]pyrimidine 1 was synthesized and evaluated in th e Geller-Seifter conflict test for anxiolytic activity to discover a l ess toxic derivative. Analysis of the SAR revealed that the most poten t compounds were those with meta substituents on the benzylamino ring. In this group the most promising derivatives were )]benzylamino-2-met hyl-7H-pyrrolo[2,3-d]pyrimidine 12 and 4-(3,5-dimethylbenzylamino)-2-m ethyl-7H-pyrrolo [2,3-d]pyrimidine 24. Potential metabolites of 12 wer e synthesized and checked for their anxiolytic activity. Less toxic an alogues of the second lead 24 were prepared by extending the alkyl gro ups attached to the benzene ring moiety. The addition of a fluoro subs tituent to the benzene moiety in the extended alkyl chain analogue obe nzylamino)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine 34 resulted in a compo und with a longer duration of activity relative to its analogue lbenzy lamino)-2-methyl-7H-pyrrolo[2,3-d]pyrimidine 26. (C) Elsevier, Paris.