Synthesis of some 6-[4-(substituted pyrrol-1-yl)phenyl]-4,5-dihydro-3(2H)-pyridazinone and 1(2H)-phthalazinone derivatives and their antihypertensive activities

ABSTRACT PhD. Thesis SYNTHESIS OF SOME 6-[4-(SUBSTITUTED PYRROL-l-YL)PHENYL]- 4,5-DIHYDRO-3(2H)-PYRIDAZINONE AND 1(2H)-PHTIIALAZINONE DERIVATIVES AND THEIR ANTD3YPERTENSIVE ACTIVITIES Ahmet Çağrı KARABURUN Anadolu University Institute of Health Sciences Department of Pharmaceutical Chemistry Supervisor: Prof. Dr. ŞEREF DEMHtAYAK 2003 During our literature research it was observed that pyridazinone derivatives possess antihypertensive, positive inotropic, platelet aggregation inhibitor and antiasthmatic effects on cardiovascular system. Considering the 6- aryl-3(2H)-pyridazinone residue as the pharmacophoric group for the above mentioned activities, in this thesis; some novel derivatives of this class were synthesised. inThe syntheses of 6-[4-(substituted pyrrol-l-yl)phenyl]-4,5-dihydro-3(2H)- pyridazinone, 2-methyl-6-[4-(substituted pyrrol-l-yl)phenyl]-4,5-dihydro-3(2H)- pyridazinone, 2-(2-acetyloxyethyl)-6-[4-(substituted pyrrol-l-yl)phenyl]-4,5- dihydro-3(2H)-pyridazinone derivatives along with 4-[4-(substituted pyrrol-1- yl)phenyl]-l(2H)-phthalazinone and 2-methyl-4-[4-(substituted pyrrol- 1- yl)phenyl]-l(2H)-phthalazinone derivatives were aimed in this work. To accomplish this primarily the starting materials were obtained in two groups as 2- substituted/non substituted 6-(4-aminophenyl)-4,5-dihydro-3(2H)-pyridazinones or 2-substituted/non substituted 4-(4-aminophenyl)-l(2H)-phthalazinones and 1- aryl-3-carbethoxy- 1,4-pentadiones. Above mentioned aminophenyl derivatives were reacted with suitable 1,4- diketon compound in acetic acid under Paal-Knorr pyrrole synthesis conditions to obtain the aimed compounds. Physical properties, Rr values on thin layer chromatography and UV absorption properties of the synthesised compounds were determined and their structures were elucidated by TR, 'H-NMR, MS spectra and elemental analysis results. Antihypertensive activities of fourteen compounds, which were selected as prototypes, were investigated as their relaxation responses to phenylephrine (Phe) contractions and remarkable activity was obtained. Keywords: Pyridazinone, Phthalazinone, Pyrrole, Antihypertensive activity IV ^£7ûK^ö6RCTiM-Ban5îJ'