6-(Alkylamino)-9-benzyl-9H-purines. A new class of anticonvulsant agents

Abstract

Several 9-alkyl-6-substituted-purines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures (MES) in rats. Most compounds were prepared in three steps from 5-amino-4,6-dichloropyrimidine or in two steps via alkylation of 6-chloropurine. Potent anticonvulsant activity against MES resided in compounds that contain a benzyl substituent at the 9-position of 6-(methylamino)- or 6-(dimethyl-amino)purine. Among commonly used agents for control of seizures, this type of structure represents a new class of potent anticonvulsant agents.

Synthesis of 5-Alkoxythieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine Derivatives and Evaluation of Their Anticonvulsant Activities

“…When 2,4-dichlorothieno[3,2-d]pyrimidine were refluxed in N,N- dimethylformamide (DMF) with different azoles such as triazole, imidazole and pyrazole in the presence of K 2 CO 3 [ 20 , 21 ], the 4-chlorine atom of 1 was easily substituted by these heterocycles, producing the corresponding thienopyrimidines 2-chloro-4-(1 H -1,2,4-triazol-1-yl)thieno[3,2- d ]pyrimidine ( 6 ), 2-chloro-4-(1 H -imidazol-1-yl)thieno[3,2- d ]pyrimidine ( 8 ), and 2-chloro-4-(1 H -pyrazol-1-yl)thieno[3,2- d ]pyrimidine ( 10 ). The target compounds 7a – d , 9a – d , and 11a – d were obtained by reacting compounds 6 , 8 , and 10 with a substituted phenol in DMF in the presence of K 2 CO 3 .…”

9-(Cyclohexylmethyl)-6-(dimethylamino)-9H-purine

“…Its activity against maximum electroshock-induced seizures was evaluated as moderate. An effective dose, ED 50 , is 25 mg kg -1 for an ip admission in rats (Kelley et al, 1988). The compound was also tested for an activity against apomorphine-induced aggresive behavior (Kelley et al, 1997), but the results were negative.…”

Importance of HMBC and NOE 2D NMR techniques for the confirmation of regioselectivity

“…The occurrences of the purine core in various natural sources have generated immense interest because of its remarkable therapeutic potentials. Among them, an extensive array of 6‐amino‐substituted derivatives of purine exhibits anticonvulsant, antiviral, anti‐inflammatory, antineoplastic, antiasthmatic, and antibacterial activities. Moreover, natural purines are found to be the core skeleton of nucleic acid, which are directly correlated with enzymes and proteins …”