6-Aryl-4,5-dihydro-3(2H)-pyridazinones. A new class of compounds with platelet aggregation inhibiting and hypotensive activities

Abstract

This paper reports on the synthesis and pharmacological activity of 6-aryl-4,5-dihydro-3(2H)-pyridazinone derivatives. The compounds exhibit an aggregation inhibiting action on human platelets in vitro and on rat platelets under ex vivo conditions, as well as a hypotensive action on rats. The strongest pharmacological effects were found with dihydropyridazinones, which have a 6-[p-[(chloroalkanoyl)amino]phenyl] substituent, together with a methyl group in the 5-position. The antiaggregation activity of compounds of this type is in vitro up to 16000 times and ex vivo up to 370 times greater than that of acetylsalicylic acid; the hypotensive action is up to 40 times as great as that of the comparative substance dihydralazine.

Pyridazine and phthalazine derivatives with potential antimicrobial activity

“…The literature describes a large variety of pyridazine and phthalazine compounds (1) with different biological activities: anticancer [1,2], antituberculosis [3], antimicrobial [4][5][6], antihypertensive [7][8][9], platelent aggregation inhibitor [9,10], etc. A facile way to obtain diazine derivatives uses cycloimmonium ylides as reactive species [11][12][13][14][15].…”

“…The problems of stereo-and regiochemistry involved in these types of cycloadditions are discussed. Considering the pyridazine -acetophenone skeleton (2) as the pharmacophoric group for the activity [4,9], in this work we aimed to obtain new diazine heterocycles with antimicrobial activity, having in mind three structural modifications: introduction of a pyrrolo (I) and/or a benzene (II) ring, and a substituient (R). In equal measure, we were interested in the chemistry of cycloaddition reactions.…”

Synthesis of 5‐(6‐Pyridazinone‐3‐yl)‐2‐Glycosylamino‐1,3,4‐Oxadiazoles

“…The IR spectra were recorded in KBr pellets on a Brucker Equinox-55 FT-IR apparatus. The 1 H NMR spectra were recorded on an INOVA-400 (using TMS as internal standard, DMSO-d 6 or CDCl 3 -d 6 as solvent). Mass spectra were recorded on an HP 1100 LC-MS (ESI).…”

“…The active compounds are how available for this indication. 6 Over the past few years, a number of pyridazine derivatives have been applied to antiarrhythmics and antianginals; some structurally related pyridazines possessing a prolinol moiety have also been considered. 7 6-Phenyl-4,5-dihydro-3(2H)-pyridazinones possessed reproducible activity in a rat hypotensive screening program.…”

Investigation of furo[2,3-h]- and pyridazino[3,4-f]cinnolin-3-ol scaffolds as substrates for the development of novel HIV-1 integrase inhibitors

“…7,8 Starting from the simple benzoylpyruvic acid 1 (BPA, Figure 1a In the course of our drug discovery program focused on developing original IN inhibitors, 10-15 a series of polycyclic templates carrying a novel potential chelating pharmacophore has been designed and synthesized. Our attention was addressed to the furo [2,3-h]cinnolin-3(2H)-one scaffold I (Figure 2), as analogue of the previoulsy reported 6-aryl-5-methyl-4,5-dihydro-3-(2H)pyridazinones, 4,4a-dihydro-5H-indeno [1,2-c]pyridazinones II, III, [16][17][18][19] and more strictly to 5,6-dihydrobenzo[h]-, 5,6-dihydrothieno [2,3(3,2)-h]cinnolin-3(2H)-ones IV, V. [20][21][22] These condensed ring systems demonstrated a versatile platform to incorporate a pyridazinone ring, which has shown several pharmaceutical properties. 23 In this context, the N-NH-CO-C-R (R = OH, NH2) motif could be considered as a potential chelating fragment, eventually suitable of bioisosteric replacement of the β-diketo enol pharmacophore.…”