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Biomedical subjects

G Pifferi

Publications and source records attributed to G Pifferi.

At least 37 records · Page 2Linked to original sources
PubMed1984

High-performance liquid chromatographic separation of cadralazine from its potential metabolites and degradation products. Quantitation of the drug in human plasma and urine.

The chromatographic behaviour of cadralazine and its potential metabolites and degradation products with respect to pH, buffer molarity and composition of eluent is described. A selective method with an adequate sensitivity for the determination of the drug in human plasma and urine is also reported. The method includes extraction of biological fluids with chloroform and the analysis of extracts on a reversed-phase column with isocratic elution and detection at 254 nm. The method has been applied to the analysis of plasma and urine of a patient administered a single oral dose of 30 mg of cadralazine.

Antihypertensive Agents↗
PubMed1984

Degradative behavior of cadralazine in aqueous solution.

The degradation of cadralazine in aqueous solution was investigated in relation to pH, concentration, and temperature, under aerobic and anaerobic conditions in light and dark. The appearance of three main degradation products was also studied. Drug disappearance was dependent on temperature, pH, concentration, and oxygen and followed three different mechanistic pathways: thermal, hydrolytic, and oxidative. The individual rate constants were determined by nonlinear regression fitting.

Air↗
PubMed1983

Synthesis and antibacterial activities of new (alpha-hydrazinobenzyl)cephalosporins.

Some (alpha-hydrazinobenzyl)cephalosporins, I (R = Me, CH2OAc, Cl) and II (R = Me, CH2OAc), structurally related (formula; see text) to cephalexin, cephaloglycin, and cefaclor have been prepared and evaluated in vitro for their antimicrobial activity. The synthesis involves the condensation of the chloride hydrochloride III (R = H or Me) with the 7-aminocephem derivatives IV. The hydrazino compound I (R = Cl), an analogue of cefaclor, resulted in being the most active compound of the series.

Bacteria↗
PubMed1981

High-performance liquid chromatographic determination of trithiozine and its neutral metabolites in human plasma and urine.

A high-performance liquid chromatographic method for the quantitation of the new anti-secretory and antiulcer drug trithiozine in human plasma and urine is reported. The procedure is simple and precise; it allows the simultaneous determination of therapeutic doses of the drug and its three main metabolites, namely, 4-(3,4,5-trimethoxythiobenzoyl)tetrahydro-1,4-oxazine S-oxide, 4-(3,4,5-trimethoxybenzoyl)tetrahydro-1,4-oxazine, and 2-hydroxy-4-(3,4,5-trimethoxybenzoyl)tetrahydro-1,4-oxazine.

Anti-Ulcer Agents↗
PubMed1981

Degradation of propildazine in water.

Propildazine degradation in water at pH 7.4 was studied under aerobic conditions. Three main products were isolated by column chromatography and identified on the basis of IR, UV, and NMR spectroscopy and mass spectrometry and by comparison with synthetic samples. Drug disappearance in water was monitored by UV spectroscopy and was concentration, pH, temperature, and oxygen dependent. Propildazine degradation also was followed in methanol at various pH values.

Antihypertensive Agents↗
PubMed1981

Cyclic GABA-GABOB analogues. III - Synthesis and biochemical activity of new alkyl and acyl derivatives of 4-hydroxy-2-pyrrolidinone.

The synthesis of new N-substituted 4-hydroxy (III) and 4-acyloxy- or 4-alkoxy-2-pyrrolidinones (IV), as analogues of oxiracetam (III c), is reported. For this purpose, a convenient procedure for N-alkylation of the base-labile 4-hydroxy-2-pyrrolidinones (II a, c, d) was developed. Compounds (III) and (IV) were examined on phospholipid synthesis in brain microsomal membranes of rats, both in vivo and in vivo-in vitro, and on protein synthesis in brain slices. Results showed that only oxiracetam (III c), and to a lesser extent piracetam, are active both on phospholipid and brain protein synthesis.

Animals↗
PubMed1980

Synthesis of N-alkoxybenzoylmorpholinols as possible metabolites of trithiozine.

The synthesis of some possible metabolites of trithiozine, a new antisecretory-antiulcer drug, is reported. The metabolite 4-(3,4,5-trimethoxybenzoyl)-2-morpholinol (III a) was prepared by oxidative cyclization of the corresponding diethanolamine derivative (II a). Similarly, 4-syringoyl-2-morpholinol (III c) was also obtained and both were converted into the methyl ethers (IV a, c), respectively. The same oxidative approach, starting from the alcohol (VII), afforded the isomeric 4-(3,4,5-trimethoxybenzoyl)-3-morpholinol (IX a) in low yields; therefore a four step process, involving the acid hydrolysis of the acetal intermediate (XII a) was preferred. In the course of the synthetic work 4-(3,4,5-trimethoxybenzoyl)-3-morpholone (V), a potential metabolite itself, was also prepared.

Anti-Ulcer Agents↗
PubMed1979

[3-Hydrazinepyridazine derivatives. III. Synthesis and anti-hypertensive activity of new 3-(2-acylhydrazine)-pyridazine-6-alkylamino substitutes].

The synthesis of 2-(6-dialkylamino-3-pyridazinyl)hydrazinecarboxylates (II) and hydrazides (V) from the corresponding 3-chloro-6-dialkylaminopyridazines (I) is described. The 6-substituted derivatives of 2,3-dihydro-1,2,4-triazolo[4,3-b]pyridazine-3-ones (III) and 1,2,4-triazolo[4,3-b)pyridazines (VI) were obtained by thermal cyclization of (II) and (V), respectively. The new acyl derivatives were evaluated together with todralazine and budralazine as antihypertensive agents in comparison with propildazine and hydralazine. The ethoxycarbonyl compound [(II g), ISF 2469] exhibits good antihypertensive activity particularly via oral administration. Its interesting pharmacodynamic properties, including slow onset and long-lasting action, qualify it for further pharmacological and clinical studies.

Animals↗
PubMed1978

Quantitative determination of propildazine in rat plasma by gas-liquid chromatography.

A gas-liquid chromatographic method for the evaluation of the new anti-hypertensive drug propildazine (ISF 2123) in rat plasma is described. The procedure involves separation of the drug from plasma by cation-exchange chromatography, subsequent acylation of the dried eluate with heptafluorobutyric anhydride and quantitation with electron-capture detection. Propildazine can be determined in concentrations down to ca. 0.4 microgram/ml.

Animals↗
PubMed1978

Convenient synthesis of (RS)-4-amino-3-hydroxybutyric acid.

A new three-step synthesis of 4-amino-3-hydroxybutyric acid from an inexpensive starting material and under mild reaction conditions is described. Crotonic acid was brominated by the Wohl-Ziegler reaction to 4-bromocrotonic acid, which, in turn, was converted with ammonium hydroxide into 4-aminocrotonic acid. This compound, refluxed in water in the presence of a strong acid resin, afforded 4 amino-3-hydroxybutyric acid in good yields.

Aminobutyrates↗
PubMed1978

Cyclic GABA-GABOB analogues. II - Synthesis of new 2-oxo and 2,5-dioxo-delta3-pyrroline derivatives.

Within the framework of a research program on new compounds potentially active on learning and memory processes, some esters and amides of 2-oxo- and 2,5-dioxo-delta3-pyrroline-1-acetic acids were synthesized. Such compounds can be regarded either as dehydration products of the corresponding 4-hydroxy-2-pyrrolidinones or as cyclic derivatives of 4-aminoisocrotonic acid. Two approaches were used in an attempt to synthesize pyrrolinone derivatives. One method involved the direct alkylation with ethyl bromoacetate of 1,5-dihydro-2H-pyrrol-2-one (III b), obtained for the first time in pure form by cyclization of 4-amino-3-hydroxybutyric acid (GABOB). Another approach involved the preparation of the ethyl 3-bromo-2-oxo-1-pyrrolidineacetate (VI), by cyclization of N-(2,4-dibromobutyryl)glycine ethyl ester (V), and its 4-bromo isomer (X b) by bromination of ethyl 4-hydroxy-2-oxo-1-pyrrolidineacetate (X a). While the dehydrobromination of (VI) was unsuccessful, heating of (X b) with TEA afforded ethyl 2,5-dihydro-2-oxo-1H-pyrrole-1-acetate (IV a). Alternatively, (X a) was treated with methanesulfonyl chloride, then with TEA to give (IV a). Final ammonolysis of (IV a) provided the corresponding amide (IV b). For the synthesis of the maleimide analogue (XIII b), the N-(carboxymethyl)maleamic acid (XII a) was treated with PCl5 and then with anhydrous ammonia.

Acetates↗
PubMed1978

[Derivatives of 3-hydrazinopyridazine. II. Synthesis and antihypertensive activity of new 3-hydrazino-6-monoalkylaminopyridazines].

The synthesis of some 3-hydrazino-6-monoalkylaminopyridazines (VIII) by reaction of 3,6-dichloropyridazine with various N-monoalkylbenzylamines, followed by reaction with hydrazine and final debenzylation in an acidic medium, is described. The new compounds were evaluated as antihypertensive agents and exhibited the same or higher activity than hydralazine, but lower activity than propildazine (ISF 2123).

Animals↗
PubMed1977

Semisynthetic beta-Lactam antibiotics. II. Penicillins from alpha-hydrazinoarylacetic acids.

A number of penicillins (2) have been synthesized from the alpha-hydrazinoarylacetic acids (4) via the activated chloride hydrochlorides (5) or via the mixed anhydride of the corresponding N2-benzyloxycarbonyl derivatives (6). The penicillins, 2b, e, j, show good activity against gram-positive and gram-negative bacteria and enhanced penicillinase resistance in comparison with ampicillin.

Acetates↗
PubMed1977

Synthesis and antiinflammatory activity of 3-chloro-4-cyclopropylmethoxyphenylacetic acid and its alpha-methyl homologue.

The synthesis of 3-chloro-4-cyclopropylmethoxyphenylacetic acid (I) from 3-chloro-4-hydroxyacetophenone (III) by the etherification with cyclopropylmethyl bromide and by the Willgerodt reaction is described. The alpha-methyl homologue (II) was also prepared from 4-benzyloxy-3-chlorophenylacetate (VIII). The antiinflammatory, analgesic and antipyretic activities of the lysine salts of (I) (ISF 2508) and (II) (ISF 2606) were tested in comparison with alclofenac and phenylbutazone. The new ocmpounds compare favourably with the standards; in particular ISF 2508 was selected for further pharmacological studies.

Analgesics↗
PubMed1977

Cyclic Gaba-Gabob analogues I - Synthesis of new 4-hydroxy-2-pyrrolidinone derivatives.

In the event that the GABA-GABOB system is involved in the initial phases of the learning and memory process, some new derivatives of 4-hydroxy-2-pyrrolidinone (I a) have been synthesized. The cyclic compounds of general formula (A) are more lipophilic than GABOB and should better enter brain fluids. The N-hydroxymethyl derivatives (II a...c) were prepared by addition of the suitable aldehydes to 4-acetoxy-2-pyrrolidinone (I b). In order to obtain the ethyl 4-hydroxy-2-oxo-1-pyrrolidineacetate (IV a) some synthetic routes starting from (I b), (III b) and from the 3-diazotetramic acid (V) were explored. However, the N-ethoxycarbonylmethyltetramic acid (X), obtained by Dieckmann cyclization of triester (VIII) and subsequent de-etho-xycarbonylation was reduced to (IV a). Ammonolysis of (IV a) afforded the acetamide (XI a). The O-acetyl derivatives (IV b) and (XI b) were also prepared.

Aminobutyrates↗
PubMed1977

Biotransformation of trithiozine. III - Isolation and identification of further metabolites in rat urine.

The metabolism of a new antisecretory and antiulcer drug, trithiozine (I.S.F. 2001, T), was studied in 4 hr rat urine samples after i.p. administration. After extraction at pH 7 with chloroform, the urine was either incubated with beta-glucuronidase or acidified to pH 2 and subsequently extracted with chloroform. The organic layers were evaporated to dryness and the residues used for TLC analysis. The neutral extracts revealed five spots, not present in control rat urine, corresponding to the unchanged drug T and to four metabolites. Two of the metabolites had been previously identified as the 4-(3,4,5-trimethoxybenzoyl)tetrahydro-1,4-oxazine (TBO) and the 4-(3,4,5-trimethoxythiobenzoyl)tetrahydro-1,4-oxazine-S-oxide (TO). Three other metabolites were found in the extracts after beta-glucuronidase incubation. TLC, U.V. and M.S. data were consistent with the structure 4-(3,5-dimethoxy-4-hydroxythiobenzoyl)tetrahydro-1,4-oxazine (HT), the corresponding S-oxide (HO) and the 4-(3,5-dimethoxy-4-hydroxybenzoyl)tetrahydro-1,4-oxazine (HBO). The acidic extracts revealed two spots structurally identified as the 3,4,5-trimethoxybenzoic acid (TBA) and the previous HBO. On the basis of present knowledge, a possible metabolic pathway of T is reported, consisting in a rapid metabolic oxidation on the sulfur atom and a slower demethylation on the para methoxy group. The presence of TBA is indicative of subsequent enzymatic hydrolysis of TBO. The intense and long-lasting inhibitory effect of T on gastric secretion is tentatively correlated with the pharmacological activities of some of its metabolites.

Animals↗