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41.
1‐[(Imidazolidin‐2‐yl)imino]‐1H‐indoles as new hypotensive agents: synthesis and in vitro and in vivo biological studies 下载免费PDF全文
Anita Kornicka Aleksandra Wasilewska Jarosław Sączewski Alan L. Hudson Konrad Boblewski Artur Lehmann Karol Gzella Mariusz Belka Franciszek Sączewski Maria Gdaniec Apolonia Rybczyńska Tomasz Bączek 《Chemical biology & drug design》2017,89(3):400-410
A series of 1‐[(imidazolidin‐2‐yl)imino]‐1H‐indole analogues of hypotensive α2‐AR agonists, 1‐[(imidazolidin‐2‐yl)imino]‐1H‐indazoles, was synthesized and tested in vitro for their activities at α1‐ and α2‐adrenoceptors as well as imidazoline I1 and I2 receptors. The most active 1‐[(imidazolidin‐2‐yl)imino]‐1H‐indoles displayed high or moderate affinities for α1‐ and α2‐adrenoceptors and substantial selectivity for α2‐adrenoceptors over imidazoline‐I1 binding sites. The in vivo cardiovascular properties of indole derivatives 3 revealed that substitution at C‐7 position of the indole ring may result in compounds with high cardiovascular activity. Among them, 7‐fluoro congener 3g showed the most pronounced hypotensive and bradycardic activities in this experiment at a dose as low as 10 μg/kg i.v. Metabolic stability of the selected compounds of type 3 was determined using both in vitro and in silico approaches. The results indicated that these compounds are not vulnerable to rapid first‐phase oxidative metabolism. 相似文献
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Magdalena Wróblewska Joanna Kasprzyk Franciszek Sączewski Anita Kornicka Konrad Boblewski Artur Lehmann Apolonia Rybczyńska 《Pharmacological reports : PR》2013,65(4):1025-1032
BackgroundWe have recently described the synthesis and circulatory properties of two novel centrally acting imidazoline agents: marsanidine (1-[(imidazolidin-2-yl)imino]indazole) and 7-Me-marsanidine (1-[(imidazolidin-2-yl)imino]-7-methylindazole). Marsanidine has proven to be a highly selective α2-adrenoceptor ligand with the α2/I1 selectivity ratio of 3879, while 7-Me-marsanidine has been shown to be a mixed α2-adrenoceptor/imidazoline I1 receptor agonist with the α2/I1 selectivity ratio of 7.2. In the same paper, we indicated that iv administration of both compounds toWistar rats induced a decrease in blood pressure and heart rate. The hypotensive effect of the iv administered imidazolines might be mediated not only through activation of the central α2 and/or I1 receptors but also through subsequent decrease of the renal sympathetic nerve activity and a direct effect on peripheral receptors. The present studies were performed to determine whether the newly synthesized compounds might influence the diuresis and sodium excretion in rats.MethodsBoth compounds were infused iv to anesthetized rats in the dose of 100 μg/kg b.w. The diuresis and sodium concentration in urine and blood samples were determined. The mean arterial blood pressure and heart rate were monitored directly throughout the experiment.ResultsAsignificant increase of diuresis and natriuresis was observed within 40 min after the administration of both marsanidine and 7-Me-marsanidine, in comparison to both the control period and the control group. However, between the 20 and 40 min of the experiment the natriuretic and diuretic effect of 7-Me-marsanidine was markedly higher than that of marsanidine.ConclusionOur study indicates that the new hypotensive imidazoline compounds of marsanidine and 7-Me-marsanidine increase diuresis and natriuresis in rats. However, the effect of 7-Me-marsanidine is markedly more potent, probably due to its moderate affinity to the I1-imidazoline receptor. 相似文献
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Castellano I Covarsí A Novillo R Gómez-Martino JR Ferrando L 《Nefrología : publicación oficial de la Sociedad Espa?ola Nefrologia》2002,22(2):162-169
Diabetic glomerulosclerosis is the most frequent cause of renal disease in patients with type II diabetes mellitus (DM), sometimes accompanied by vascular lesions. However, other glomerular pathologies are important in these patients. The aim of this study was to evaluate the prevalence of non-diabetic nephropathy (NDN) in selected patients with type II DM, and to identify clinical markers that may predict its presence in this population. We reviewed 20 renal biopsies performed on twenty patients with type II DM. Nine of them showed diabetic nephropathy (DN) (45%), whereas eleven showed NDN (55%): 1 IgA nephropathy, 3 vasculitis and 7 membranous nephropathy. We found no differences between the two groups with regard to sex, duration of DM, insulin therapy, glycosylated haemoglobin, proteinuria, presence of nephrotic syndrome, hypertension, serum IgA level or renal size. The NDN group had haematuria in 63.6%, whereas the patients with NDN had it in 44.4% (NS). Body mass index was higher in NDN patients (30 +/- 6.7 vs 22 +/- 2.9; p < 0.01), The same was true for creatinine clearance (82.2 +/- 51.4 ml/m vs 40.4 +/- 19.6 ml/m; p < 0.05). The age at the moment of diagnosis was higher in ND patients (67 +/- 11.2 vs 54.3 +/- 4.6; p < 0.05). The 3 patients who had diabetic retinopathy were found to have DN on renal biopsy (diagnostic specificity = 100%), although 66.7% of the patients with diabetic glomerulopathy had no retinopathy. We conclude that patients with type II DM with renal findings suggesting non-diabetic renal disease frequently it have NDN, and a renal biopsy must be performed. The presence of retinopathy has a predictive value of 100% in predicting DN, therefore its existence may make this diagnostic procedure unneccesary. 相似文献
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J Ocon Pujadas R Novillo J Ferré G del Río R Castellet F Izquierdo F Algaba 《Urologia internationalis》1986,41(2):95-101
We studied 37 patients with various degrees of hypertension and a small unilateral kidney. Renal vein renin studies were shown to be positive on 19 occasions and negative on 18. Of those positive, 10 had severe and 1 moderate hypertension. Surgery cured 63.3%. In 27% blood pressure improved and 1 patient failed to respond. Eight patients had mild hypertension with a positive renal vein renin ratio (RVRR), but on observation their home blood pressures were normal without medication and they were not considered for surgery. Eighteen patients with mild hypertension and negative RVRR were also not operated. We believe that RVRR is important for a surgical decision, but only in severe and moderate hypertensives. In mild hypertension, measurement of blood pressure at home is normal on most occasions. These are hyperreactive patients and should not have surgery, regardless of the results of their RVRRs. 相似文献
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Antón-Pacheco Sánchez J García Vázquez A Cuadros García J Cano Novillo I Villafruela Sanz M Berchi García FJ 《Cirugía pediátrica : organo oficial de la Sociedad Espa?ola de Cirugía Pediátrica》2002,15(4):135-139
Tracheomalacia is an unfrequent disease that causes tracheal collapse during breathing. It is generally associated to esophageal atresia, but cases of primary tracheomalacia and others secondary to extrinsic compression, have also been described. Spontaneous resolution is generally the rule and only a few cases need surgical treatment. When this therapy fails or is not indicated for any reason, endoluminal tracheobronchial stents may be used. We have treated two patients with four expandable metallic stents: one had severe tracheomalacia associated to esophageal atresia and the other tracheobronchomalacia secondary to cardiomegaly. Results have been good in both cases. 相似文献
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García Vázquez A Cano Novillo I Portela Casalod E Benavent Gordo MI Berchi García FJ 《Anales espa?oles de pediatría》2002,56(3):258-260
The colon is the least common site of congenital intestinal stenosis and atresia and accounts for 5-15 % of all of these abnormalities. We present the case of a 2-month-old boy who presented vomiting, constipation, weakness, and abdominal distension. Contrast enema and colonoscopy revealed an abrupt change in caliber in the sigmoid colon and, after ruling out other disorders, a diagnosis of colonic stenosis was made. Laparoscopy under total anesthesia was performed and a stenotic area in the sigmoid colon and proximal dilatation were identified. A small incision was made and the stenotic segment was removed. Video-assisted resection and end-to-end anastomosis were performed and the child made and uneventful postoperative recovery. Contrast enema after surgery showed good anastomosis and normal bowel diameter. At the age of 18 months the patient is asymptomatic and his stools are normal. With laparoscopy, visualization of the abdominal cavity was magnified and detailed, the affected intestinal segment was easily identified and other diseases were ruled out. Recovery was rapid and the functional and esthetic results were excellent. 相似文献
50.
Saczewski F Kornicka A Rybczyńska A Hudson AL Miao SS Gdaniec M Boblewski K Lehmann A 《Journal of medicinal chemistry》2008,51(12):3599-3608
Novel benzazole derivatives bearing a (imidazolidin-2-yl)imino moiety at position 1 or 2 were synthesized by reacting 1-amino- or 2-aminobenzazoles with N, N'-bis( tert-butoxycarbonyl)imidazolidine-2-thione in the presence of HgCl 2. Structures of 1-[(imidazolidin-2-yl)imino]indazole (marsanidine, 13a) and free base of the 4-Cl derivative 12e were confirmed by X-ray single crystal structure analysis. Compound 13a was found to be the selective alpha 2-adrenoceptor ligand with alpha 2-adrenoceptor/imidazoline I 1 receptor selectivity ratio of 3879, while 1-[(imidazolidin-2-yl)imino]-7-methylindazole ( 13k) proved to be a mixed alpha 2-adrenoceptor/imidazoline I 1 receptor agonist with alpha 2/I 1 selectivity ratio of 7.2. Compound 13k when administered intravenously to male Wistar rats induced a dose-dependent decrease in mean arterial blood pressure (ED50 = 0.6 microg/kg) and heart rate, which was attenuated following pretreatment with alpha 2A-adrenoceptor antagonist RX821002. Compound 13a may find a variety of medical uses ascribed to alpha 2-adrenoceptor agonists, and its 7-methyl derivative 13k is a good candidate for development as a centrally acting antihypertensive drug. 相似文献