2-Amino-6-chloro-4-(N-methylpiperazino)pyrimidines, inhibitors of spiroperidol binding.
A series of 30 6-chloro-2,4-diaminopyrimidines was synthesized and tested in vitro as inhibitors of [3H]spiroperidol binding. The affinity for the dopamine receptor was shown to be related to the 6-chloro-4-(N-methyl-piperazine)pyrimidine structure bearing a NH2 or NHR1 group as a substituent in position 2, provided that R1 was not an alpha branched alkyl group. The nature of the substituent in position 5 is also of importance for the affinity; 2-(benzylamino)-6-chloro-4-(N-methylpiperazino)-5-(methylthio)pyrimidine (22) is the most active member of the series. Molecular structures of three compounds were analyzed by X-ray diffraction and PCILO computation.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002090:Butyrophenones / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D003461:Crystallography; D006220:Haloperidol / Q000378:metabolism; D066298:In Vitro Techniques; D008968:Molecular Conformation; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D013134:Spiperone / Q000378:metabolism*; D014961:X-Ray Diffraction
D002090:Butyrophenones; D010879:Piperazines; D011743:Pyrimidines; D011954:Receptors, Dopamine; D013134:Spiperone; D003024:Clozapine; D006220:Haloperidol