SYNTHESIS OF SOME AMINO-4,5-DIHYDROPYRAZOLO[3,4-A]ACRIDINES AS POTENTIAL CHOLINESTERASE-INHIBITORS

A synthesis of the 4,5-dihydro derivatives of the previously known pyrazolo[3,4-a]acridine ring system is described. The reaction of a 3,4-dihydroacridin-1(2H)-one with N,N-dimethylformamide dimethyl acetal gave a reactive enamino ketone, which yielded the desired heterocycle upon reaction with hydrazine. Using this chemistry, 11-amino-4,5-dihydro-2H-pyrazolo[3,4-a]acridine (3) and a number of its 2-substituted derivatives 4a-k were synthesized and evaluated as acetylcholinesterase inhibitors, based on their relationship to 1,2,3,4-tetrahydro-9-acridinamine (THA). 1-Amino-4,5-dihydro-1H-pyrazolo[3,4-a]acridine (11a) and 2-amino-4,5-dihydro-1H-pyrazolo[3,4-a]acridine (11b) were also synthesized and investigated as potential cholinesterase inhibitors.