The preparation of new 3-hydrazinothieno(2,3-h)cinnolines is described togehter with their hypotensive effects in normotensive rats.Pyridazinderivate, 6. Mitt.: Synthese und antihypertensive Eigenschaften von 3-Hydrazinthieno(2,3-h)cinnolinen und ihrer Derivate Es werden die Darstellungen neuer 3-Hydrazinothieneo-(2,3-h)-cinnoline and ihrer Derivate sowie die bei der Untersuchung ihrer antihypertensiven Eigenschaften bei Normaldruckratten erhaltenen Ergebnisse beschrieben.Hydrazinephthalazines, discovered by Druey and Gross') in 1950, are drugs used clinically as antihypertensives, the most important being hyIt is nevertheless striking that few of the hydrazinepyridazincs investigated have thiophene substituted phenyl rings with the same isosterism as benzothiophene? As part of a more extensive study of the influence of such isosterism on the antihypertensive activity of hydrazinepyridazines, we report here the synthesis and hypotensive activity of 3-hydrazinethieno(2,3-h)cinnoline 8 and some of its derivatives. dralazine (Ia) (Apresoline) and dihydralazine (Ib) (Nepresol).Structure-activity studies have found significant antihypertensive activity to be exhibited by a number of related hydrazinepyridazines, and this group of compounds continues to be an object of prospection for new drugs with greater activity and fewer side-effects (the most serious of the latter being an increase in heart rate). In this laboratory, for example, we have synthesized series of hydrazinepyridazines based on 6-phenyl-5-aminomethyl-3-hydrazinepyridazine (II)z, 6-phenyl-5-amino-3-hydrazinepyridazine (III)3, 6-phenylamino-3-hydrazinepyridazine (IVY and 3-hydrazine-5,6-dihydrobenzo(h)cinnoline (VF, most of which proved to have considerable antihypertensive properties. IV Chemistry StrategyThe target compound 8 was prepared in three stages comprising 1) the preparation of the cycloalcanone 3,2) the addition of an acetic acid group to C-5 of 3, and 3) the formation of the pyridazine ring and subsequent introduction of the hydrazine group. 1) Preparation of cycloalcanone 3.A Friedel-Crafts reaction between thiophene and succinic anhydride with aluminium trichloride as catalyst afforded the acid 1, whose reduction in diethyleneglycol by hydrazine hydrate (Huang-Minlon procedure) gave the acid 2. This acid was finally cycliced to 3 following Nishimura et al.'), which consits in warming a solution of2 in acetic anhydride to 120-130 "C 'with a catalytic amount of 85 % phosphoric acid. 2) Addition of an acetic acid group to C-5 of 3.Two methods were used: a) reaction of 3 with glyoxylic acid generated in situ lo) afforded the hydroxyacid 4a; and b) alkylation of 3 with ethyl bromacetate in the presence of lithium di-isopropylamide afforded 4b in 45 % yield.3) Formation of the pyridazine ring and addition of hydrazine.A four stage process was employed: a) 4a and 4b were refluxed with hydrazine hydrate in ethanol to give the cor-
High-density catheters combined with Orientation Independent Sensing (OIS) methods have emerged as a groundbreaking technology for cardiac substrate characterisation. In this study, we aim to assess the arrangements and constraints to reliably estimate the so-called omnipolar electrogram (oEGM). Performance was evaluated using an experimental animal model. Thirty-eight recordings from nine retrospective experiments on isolated perfused rabbit hearts with an epicardial HD multielectrode were used. We estimated oEGMs according to the classic triangular clique (4 possible orientations) and a novel cross-orientation clique arrangement. Furthermore, we tested the effects of interelectrode spacing from 1 to 4 mm. Performance was evaluated by means of several parameters that measured amplitude rejection ratios, electric field loop area, activation pulse width and morphology distortion. Most reliable oEGM estimations were obtained with cross-configurations and interelectrode spacings $$\le 2$$ ≤ 2 mm. Estimations from triangular cliques resulted in wider electric field loops and unreliable detection of the direction of the propagation wavefront. Moreover, increasing interelectrode distance resulted in increased pulse width and morphology distortion. The results prove that current oEGM estimation techniques are insufficiently accurate. This study opens a new standpoint for the design of new-generation HD catheters and mapping software.
3‐Hydrazinethieno(2,3‐h)cinnoline (IX) and its derivatives (XI) and (XIII) are prepared according to the reaction scheme.
ABGTRACTIhe electmmlwtim of the radi-itizer anti-5-nitwZ-furaldoxk (nifurmdme) ~8 studied & cmventie nal, mmul pllm and reversed pllm polarcgraphy in aqugus Mfers cmtainimg 0.75% dimethylfodde. In acid media vere CQtained f a r cathodic wavea, m l y I (related to the reductim with 4 electm of the nitro g m p ) , 11 and I11 (both linkd to the remtdim of the mi me gmup with 4 e l e c t m ) and IV (rnmspmlmg ' to the reductim of the hydrcocylaolirw, grarp f o n d i n the reactim yielding wave I). As the inrreased , Iv disappeared, I1 and I11 overlapped and I was split into wavea I' and I". Mechimirntl acarrnting for the electrode pmceseea of the wava are pmposed. lhe presere of sodiun laurylsul&ate derreased the limiting current of I' to 1/4 of that of I; under these mditims, wave I' cwmqmded to the reversible reductim of the nitm derivative to its radical-anim.
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