Synthesis and antihypertensive properties of new 3-hydrazinopyridazine derivatives

Pifferi, G.; Parravicini, F.; Carpi, C; Dorigotti, L.

doi:10.1021/jm00241a020

Cited by 31 publications

(10 citation statements)

References 3 publications

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“…Metabolites I and II were devoid of the studied activities, while metabolite III caused a dose dependent relaxation of arterial smooth muscle and its antihypertensive activity was confirmed (Pifferi, Parravicini, Carpi & Dorigotti, 1975) and found faster in onset and greater than that of cadralazine mostly after i.v. administration.…”

Section: Pmentioning

confidence: 87%

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

1981

British J Pharmacology

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Some CCK-like peptides were tested for their effects on gastric emptying in the rat, taking into account their spasmogenic action on the gastroduodenal junction observed in previous papers (Bertaccini, Impicciatore & De Caro, 1973; Bertaccini, Impicciatore, De Caro, Chiavarini & Burani, 1974). Gastric emptying of a phenol red meal was evaluated by a modification (Scarpignato and Bertaccini, 1980) of the method described by Reynell & Spray (1956). Male rats weighing 200 g were used after a fasting period of 24 h. Peptides used were: caerulein, C-terminal heptapeptide of CCK (hepta-CCK) and pentagastrin. They were injected i.p. in a constant volume of 1 ml/kg 5 min prior to administration of the meal. Rats were killed at various time intervals to evaluate the duration of the effect. A fixed time (20 min) was selected for the study of the dose-response relationship. All the peptides delayed gastric emptying in a dosedependent fashion: threshold doses were 0.075 .g/kg for caerulein and hepta-CCK. Both peptides caused a complete block of gastric emptying with doses of 5 gg/kg. Pentagastrin had a threshold dose at 10 pg/kg; the maximum dose (80 pg/kg) caused an 104P PROCEEDINGS OF THE B.P.S., 30th JUNE, 1st JULY, 1980 Table I 'Characteristics' of emptying patterns Calculated Half-life emptying time Treatment (min) (min) Controls 15.3 + 6.2' 120.9 + 6.1 Caerulein (1 bg/kg) 49.0 + 14.32 220.6 + 14.32 Hepta-CCK (1 p.g/kg) 53.3 + 14.32 289.3 + 14.22 Pentagastrin (80 bg/kg) 23.8 + 7.73 146.0 + 7.73 1 Mean value + 95W confidence limits. 2 Statistically significant difference (P < 0.001) in comparison with control values. Statistically significant difference (P < 0.01) in comparison with control values. suggest that the delay in gastric emptying induced by CCK-like peptides is connected with the contraction of the pylorus pointed out in previous studies. Therefore the pyloric sphincter appears to play an important role in the regulation of emptying of liquids in rats, unlike cats and dogs (Stemper & Cooke, 1976) in which gastric emptying of liquids was shown to be independent of the gastroduodenal junction.

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Section: Pmentioning

confidence: 87%

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

1981

British J Pharmacology

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“…m.p. 51–53 °C) [49] . 1 H NMR (400 MHz, CDCl 3 ) δ 7.14 (d, J =9.6 Hz, 1H, H‐4), 6.71 (d, J =9.6 Hz, 1H, H‐5), 3.56 (q, J =7.1 Hz, 4H, 2CH 2 ), 1.20 (t, J =7.1 Hz, 6H, 2CH 3 ).…”

Section: Methodsmentioning

confidence: 99%

One‐Pot and Two‐Chamber Methodologies for Using Acetylene Surrogates in the Synthesis of Pyridazines and Their D‐Labeled Derivatives

Ledovskaya

Polynski

Ananikov

2021

Chemistry An Asian Journal

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Acetylene surrogates are efficient tools in modern organic chemistry with largely unexplored potential in the construction of heterocyclic cores. Two novel synthetic paths to 3,6‐disubstituted pyridazines were proposed using readily available acetylene surrogates through flexible C2 unit installation procedures in a common reaction space mode (one‐pot) and distributed reaction space mode (two‐chamber): (1) an interaction of 1,2,4,5‐tetrazine and its acceptor‐functionalized derivatives with a CaC2−H2O mixture performed in a two‐chamber reactor led to the corresponding pyridazines in quantitative yields; (2) [4+2] cycloaddition of 1,2,4,5‐tetrazines to benzyl vinyl ether can be considered a universal synthetic path to a wide range of pyridazines. Replacing water with D2O and vinyl ether with its trideuterated analog in the developed procedures, a range of 4,5‐dideuteropyridazines of 95–99% deuteration degree was synthesized for the first time. Quantum chemical modeling allowed to quantify the substituent effect in both synthetic pathways.

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“…1) as compared with hydralazine particularly recommended the former substance for antihypertensive therapy (18). As yet, the mechanism of its relaxing effect on vascular smooth muscles remains unclear; interference with adrenergic receptor activity was not found (5).…”

Section: Introductionmentioning

confidence: 99%

Altered blood pressure response to propyldazine after repeated oral administration in conscious normotensive dogs: role of the renin-angiotensin system

et al. 1984

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The magnitude and the persistence of blood pressure reduction by propyldazine (PDZ) was investigated following treatment over a period of 4 days. The experiments were performed on 6 normotensive dogs trained to submit to puncture of the femoral artery and to stand quietly in a special frame over the experimental period of 7 to 8 hours. The first dose effect of orally administered PDZ (0.06, 0.29 and 1.42 mg/kg) on heart rate, arterial blood pressure and plasma renin activity (PRA) was compared with the effect of the substance after treatment at the same respective dosage twice daily over 4 days. The compound caused a dose-dependent decrease in blood pressure accompanied by dose-dependent increases in heart rate and PRA. With 0.06 mg/kg and 0.29 mg/kg PDZ a sustained effect on arterial blood pressure was observed, whereas with 1.42 mg/kg PDZ tolerance occurred after treatment over the 4-day period. A comparison with the effects observed previously with 1.42 and 7.1 mg/kg dihydralazine (DHZ) under identical conditions showed similar results with respect to dose-dependence of blood pressure and counterregulation (1). It is considered that with a low-dose regimen there would be no decrease in activity of PDZ, the long-term hypotensive efficacy of the drug thereby being guaranteed.

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Synthesis and antihypertensive properties of new 3-hydrazinopyridazine derivatives

Cited by 31 publications

References 3 publications

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

PROCEEDING OF THE JOINT MEETING OF THE Italian and British Pharmacological Societies

One‐Pot and Two‐Chamber Methodologies for Using Acetylene Surrogates in the Synthesis of Pyridazines and Their D‐Labeled Derivatives

Altered blood pressure response to propyldazine after repeated oral administration in conscious normotensive dogs: role of the renin-angiotensin system

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