BUILDING A MODEL OF INTERACTION AT THE NK-2 RECEPTORS - POLYCONDENSEDHETEROCYCLES CONTAINING THE PYRIMIDOINDOLE SKELETONS

The pyrazolopyrimidothiazole ring system (compound N, table II) has be en previously reported by us as a new competitive antagonist (apparent pA(2) = 7.3 equiv to 55 nM) at NK2-receptors. As part of our investig ation on polycondensed heterocycles containing the pyrimidine ring as antagonists of G-protein coupled receptors, pyrimidoindole derivatives were prepared and tested in order to probe the topography of the NK2- receptors and ascertain the pattern of frameworks that result in optim um affinity and specificity. The title indole derivatives 5, 11a-d, 12 c, 13a,b and 14b were 'de novo' designed or selected from our chemical archives and prepared by up-to-date synthetic routes, thus exploring new synthetic methodologies. According to the established graphic comp uter model, none of the tested substances exhibited activity as a cons equence of the violation of an excluded volume area due the unfavourab le position of the aromatic substituents.