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A L Miranda

Publications and source records attributed to A L Miranda.

At least 19 recordsLinked to original sources
PubMed2000

Design and synthesis of novel potent antinociceptive agents: methyl-imidazolyl N-acylhydrazone derivatives.

This paper describes recent results of design, synthesis and pharmacological evaluation of new N-heterocyclic functionalized N-acylhydrazone compounds, belonging to the 2-methyl-imidazolyl-3-acylhydrazone class (4a-e). These compounds were planned by applying the molecular simplification strategy to propose the structural modifications on the previously described functionalized imidazo [1,2-a]pyridine 3-acylhydrazone series (2), which presented an important analgesic profile. This new series (4) was synthesized in order to investigate the possible pharmacophoric contribution of the N-heteroaromatic ring and N-acylhydrazone moieties to the analgesic activity. Compounds 4a-b are the most potent antinociceptive agents from this series.

Acetic Acid↗
PubMed1999

Synthesis and antiplatelet evaluation of novel aryl-sulfonamide derivatives, from natural safrole.

In the scope of a research program aiming at the synthesis and pharmacological evaluation of novel possible antiplatelet prototype compounds, exploring bioisosterism principles for molecular design, we describe in this paper the synthesis of new aryl-sulfonamides derivatives, structurally similar to known thromboxane A2 receptor antagonists. The synthetic route used to access the new compounds described herein starts from safrole, an abundant Brazilian natural product, which occurs in Sassafras oil (Ocotea pretiosa). The results from preliminary evaluation of these novel aryl-sulfonamide compounds by the platelet aggregation inhibitory test, using rabbit PRP, induced by ADP, collagen, arachidonic acid, and U46619, identified the N-[2-(4-carboxymethoxyphenyl)ethyl]-6-methyl-3,4-methylenedioxyphe nyl- sulfonamido derivative as the most active among them, presenting in IC50 value for the U-46619-induced platelet aggregation in rabbit platelet-rich plasma: 329 microM.

Animals↗
PubMed1999

Studies on antiplatelet agents from natural safrole. II. Synthesis and pharmacological properties of novel functionalized oxime O-benzylether derivatives.

In an ongoing research program aiming at the synthesis and pharmacological evaluation of new possible prototype candidates exploring the molecular hybridation and bioisosterism principles for molecular designing, we describe in this paper the design and synthesis of a series of new functionalized oxime O-benzylethers (4a-b) and (14a-b) as antiplatelet agents based on the inhibition of arachidonic acid (AA) cascade enzymes. For the synthesis of these new bioactive derivatives we used safrole (5), a Brazilian abundant natural product, as starting material. The platelet anti-aggregating evaluation of these oxime O-benzylether compounds (4a-b) and (14a-b) in model induced by ADP, collagen and AA, has permitted to evidence an antithrombotic profile to these new derivatives, being the most active the derivative methyl [[3,4-methylenedioxyphenyl]methylene]amino]oxy]-4-methylenephenylacet ic acid (14a).

Animals↗
PubMed1998

Synthesis and pharmacological evaluation of new flosulide analogues, synthesized from natural safrole.

Four new aryl-sulfonamide derivatives (3a, 4a, 5a-b), having methylenedioxy group attached to phenyl ring, were prepared from natural safrole and evaluated as anti-inflammatory agents. The N-methylsulfonamide 3a and corresponding retrosulfonamide derivative 5a were more active than standards indomethacin and nimesulide, at the same molar concentration, in carrageenan-induced pleurisy assay.

Animals↗
PubMed1998

Synthesis and analgesic properties of new 5-thioaryl pyrazole derivatives.

A new series 5-thio aryl pyrazole derivatives were proposed aiming analgesic activity. In this work, 8 new compounds of this class were synthesized using usual synthetic methodology, having as key intermediate the 3-methyl-4-nitro-5-chloropyrazole-1-phenyl derivative and subsequent reaction with several nucleophiles sulfides. Pharmacological evaluation of this series showed analgesic activity in the some extent in especially for 5-(4-bromophenyl)-thio-3-methyl-4-nitro-1-phenylpyrazole which was the most potent in this series, presenting an analgesic action comparable to that show by dipyrone.

Analgesics, Non-Narcotic↗
PubMed1996

2-Pyridylarylhydrazone derivatives, a new class of platelet aggregation inhibitors.

A series of 2-pyridylarylhydrazone derivatives was synthesized and compared with a previously reported pyrazole series, i.e., 4-acylpyrazolylarylhydrazone and 5-pyrazolylarylhydrazone, which present antiplatelet aggregation activity. The structures of these pyridylarylhydrazone derivatives were designed on the basis of the known bioisosteric relationship of the heteroaromatic ring. The antiplatelet aggregation activity was measured in vitro on citrated platelet-rich rabbit plasma in which aggregation was induced with 5 microM ADP, 5 micrograms/ml collagen and 200 microM arachidonic acid. Eighteen compounds belonging to the pyridine series were tested at 1 mM concentration and none inhibited ADP-induced rabbit platelet aggregation. 2-(2-Formylfurane)pyridylhydrazone exhibited a highly potent inhibitory activity on arachidonic acid-induced aggregation, with an IC50 of 0.35 microM. These results suggest that the hydrazone unit and the 2-furyl moiety of the arylhydrazone framework are important pharmacophores for antiplatelet activity.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1994

Synthesis and analgesic properties of 5-acyl-arylhydrazone 1-H pyrazolo [3,4-b] pyridine derivatives.

A series of 5-acyl-arylhydrazone 1-H pyrazolo [3,4-b] pyridine derivatives (1), planned by applying classical ring isosterism, were synthesized in order to evaluate the structure-activity relationship (SAR), especially the participation of the structural acyl-arylhydrazone subunit in the analgesia. The synthetic route used produced the derivatives 1 in approximately 40% overall yield, using 9 as key intermediate. The results obtained from this study showed that in general the compounds of this series present a powerful analgesic activity in the test of abdominal contortions induced by acetic acid i.p. in albino mice, indicating the participation of the acyl-arylhydrazone moiety, as well the relevance of the substituent of the aryl ring, in the activity.

Analgesics↗
PubMed1991

Substituted pyrazolylhydrazones: a new class of platelet aggregation inhibitors.

A series of 5-pyrazolylhydrazone derivatives (I) were designed to be mixed hybrid isosteres of both BW-755C and CBS-1108 which belong to the class of dual cyclooxygenase and 5-lipoxygenase inhibitors. Pharmacological evaluation of some members of this series (Ia, 1-formyl-3,4-methylenedioxy-6-nitrobenzene-5-(1-phenyl-3-methyl-4-nit ropyrazolyl)hydrazone; Ib, 2-formylfurane-5-(1-phenyl-3-methyl-4-nitropyrazolyl)hydr azo ne;Ic, (E)-2-(formylethenylfurane)-5-(1-phenyl-3-methyl-4-nitropyrazol yl)hydrazone showed that they inhibit the in vitro platelet aggregation of citrated platelet-rich rabbit plasma induced by ADP (5 microM), collagen (5 micrograms/ml) and arachidonic acid (100 microM). Compounds Ia and Ic at 100 microM concentration showed 49% and 58% inhibition, respectively, of ADP-induced aggregation. In the arachidonic acid-induced aggregation, compounds Ia and Ib at 100 microM concentration fully inhibited platelet aggregation. All compounds significantly inhibited the collagen-induced aggregation. In contrast, indomethacin (10 microM) showed 100% and 85% aggregation inhibition against arachidonic acid and collagen, respectively, and was inactive in the ADP-induced aggregation test. These results suggest that the structure-activity relationship in this series of compounds is dependent on the hydrazone moiety at position 5 of the pyrazole ring and on the distance between the aryl ring and the pyrazole ring and that the 2-furyl ring is at the optimal distance for the maximal activity.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1977

Prosthetic valve endocarditis by opportunistic pathogens.

The incidence of endocarditis produced by the so-called "opportunists" as a complication of prosthetic valve surgery is progressively increasing in frequency and gradually transforming the clinical picture habitually associated with this disease. We report six cases of endocarditis produced by opportunistic microorganisms (two cases by Candida, and the remaining by Serratia, Actinobacillus, Acinetobacter calcoaceticus, and Bacteroides fragilis, and by Corynebacterium diphtheriae) in four male and two female patients, making special comment on our findings, diagnostic criteria, and treatment. The patients' ages ranged from 9 to 54 years, and all six patients had long-term complications, with symptoms appearing between 45 days and four years after prosthetic valve surgery. The progressive increase of this new type of prosthesis infection is favored by the indiscriminate use of certain drugs and especially by the prophylactic use of antibiotics.

Adult↗
PubMed1977

Cardiac valve replacement with the Björk-Shiley prosthesis in young patients.

Between 1971 and 1974, 26 valve replacements with the Björk-Shiley tilting disc valve prosthesis were performed in 23 children between 4 and 16 years of age. Mitral valve replacement was carried out in 11 patients, aortic valve replacement in 9 and double replacement in the other 3 patients. Several of the patients presented associated lesions which were also corrected at the same intervention, One patient died during the postoperative period; the remaining 22 all showed significant clinical remission. No incidents of thromboembolism or complications of any other nature were observed during follow-up periods of 6 to 26 months. It is our belief that the Björk-Shiley valve represents an improvement over other prostheses currently used for the surgical correction of valve disease in children.

Adolescent↗
PubMed1976

Combined mitral and aortic valve replacement with the Börk-Shiley prosthesis.

Combined mitral and aortic valve replacement with the BJORK-Shiley tilting-disc valve prosthesis was performed in 42 patients. Hospital and late mortality rates were both at the 9.5% level. No correlation was seen between mortality and combination of concomitant valve lesions. Morbidity was elevated. No episodes of embolism were observed after surgery, although one patient died of severe haemorrhage. Only one patient showed valvular dysfunction (grade 2/4 leakage), but did not require reoperation. Postoperatively, 75.7% of the patients were asymptomatic for a mean follow-up period of 21.1 months. The Björk-Shiley prosthesis offers a small gradient associated with a low profile, which constitute important advantages in multiple valve replacement.

Adolescent↗
PubMedDate not supplied

Synthesis and analgesic profile of novel N-containing heterocycle derivatives: arylidene 3-phenyl-1,2,4-oxadiazole-5-carbohydrazide.

This paper describes recent results of a research program aimed at the synthesis and pharmacological evaluation of new heterocyclic N-acylhydrazone (NAH) compounds, belonging to the arylidene (3-phenyl)-1,2,4-oxadiazolyl-5-carboxyhydrazide (8a-p) series. These compounds were structurally planned by applying the molecular hybridization strategy on previously described arylidene 1-phenylpyrazole-4-carbohydrazide (5) derivatives, considered as lead-compounds, which present potent analgesic properties. The analgesic profile of the title compounds 8a-p, evaluated in the model of abdominal constrictions induced by acetic acid, showed that the 4-methoxybenzylidene derivatives 8c and 8k were the most active ones, exhibiting a relative analgesic activity comparable with that of dipyrone 1 used as standard.

Analgesics, Non-Narcotic↗
PubMedDate not supplied

Traumatic ventricular septal defect: a case of early repair and review of the literature.

We present a case of traumatic ventricular septal defect following a stab wound of the heart. The patient was operated on within the first 24 hours after being injured, because the hemodynamic situation had deteriorated; he is well 31 months postoperatively. From the literature reviewed, it is apparent that most of such lesions should be corrected early, since these patients are exposed to the continued risk of symptomatic cardiac dysfunction, and repair offers an excellent prognosis with minimal morbidity.

Adult↗