A terc-amino effektus vizsgálata és kiterjesztése: új típusú, biológiailag aktív policiklusos vegyületek előállítása = The study and the extension of the tert-amino effect: Synthesis of new types of polycyclic compounds with biological activities

1. Vizsgaltuk a terc-amino effektus 2. tipusanak kiterjeszteset a reakcioban resztvevő vinil es terc-amino csoportot ket kulon gyűrűn tartalmazo (kondenzalt) bi- es triaril - bifenil/fenilpiridazin, trifenil/difenilpiridazin, naftalin illetve fenilnaftalin - modellvegyuletekre; a gyűrűzarasi reakciok reven uj azepin-, azocin-, azonin- es azecin-anellalt gyűrűrendszereket allitottunk elő. E munkank reven a terc-amino effektus az eddigi ismeretek szerinti alkalmazasat lenyegesen bővitettuk. 2. Antimalarias hatasiranyban nemzetkozi egyuttműkodesben vizsgaltuk azocinszarmazekok, illetve indolokinolin alkaloidok bi- es triciklusos analogjainak aktivitasat. Ez utobbiak kozul ket szarmazek is jelentős in vitro aktivitast mutatott. 3. SSAO hatasiranyban vizsgaltuk a terc-amino effektussal nyert diciano-szubsztitualt azaheterociklusokbol előallitott aminometil szarmazekok, illetve tovabbi vegyuletcsaladok (oxim tipusu vegyuletek, aminometil-piridazinok) aktivitasat; egyuttműkodesben kivalasztott SSAO-gatlok tovabbi in vivo vizsgalatara kerult sor gyulladasos modelleken. E vegyuletek egyike (SZV-1287) mind in vitro, mind in vivo jelentős SSAO-gatlo es gyulladascsokkentő hatast fejt ki; fejleszteseről a kozeljovőben dontunk. | 1. Novel extensions of the type 2 tert-amino effect have been studied to compounds having the interacting vinyl and tert-amino moieties on two different rings. Namely, cyclizations of bi- and triaryl - biphenyl/phenylpyridazine, triphenyl/diphenylpyridazine, napthalene and phenylnapthalene - model systems were studied, affording novel azepine-, azocine-, azonine- and azecine-fused ring systems. Our studies facilitate novel applications of the tert-amino effect as compared to cyclizations described thus far. 2. In the frame of an international collaboration, the antimalarial activity of azocine derivatives, and bi- and tricyclic analogues of indoloquinoline alkaloids were studied. Two representatives of the latter group exhibited substantial in vitro activity. 3. SSAO activity of aminomethyl derivatives obtained from dicyano-substituted azaheterocycles synthesized via tert-amino effect cyclization and further classes of compounds (oxime derivatives, aminomethyl-pyridazines) were studied; in collaboration in vivo activity of selected SSAO inhibitors were studied in inflammatory models. On selected derivative (SZV-1287) exhibited substantial in vitro and in vivo SSAO inhibitor and anti-inflammatory activity; we are to decide on its further development.