Synthesis of some Substituted Pyrido[1,2-a]pyrimidin-4-ones and 1,8-Naphthyridines.

The substituted 4H-pyrido[1, 2-a]pyrimidin-4-ones (I) were obtained by the condensation of substituted 2-aminopyridines with δ-ketocarboxylic esters in PPA. Some of the derivatives I were transformed into the corresponding 1, 8-naphthyridines II and III

Synthesis and evaluation of antimycobacterial activity of 4-phenyl-1,8-naphthyridine derivatives

Some 4-phenyl-1,8-naphthyridine derivatives with a piperazino group in the 2- and/or 7-position have been synthesized and evaluated for their tuberculostatic activity. The compounds 1, 6, 10, 17b,c and 19i showed a marked activity against Mycobacterium tuberculosis H(37)Rv. For this series of compounds, submitted to biological screening, no structure-activity relationship can be deduced

Pharmacokinetics of Tramadol and its Metabolites M1, M2 and M5 in Horses Following Intravenous, Immediate Release (Fasted/Fed) and Sustained Release Single Dose Administration

Tramadol (T) is a centrally acting analgesic structurally related to codeine and morphine. This drug displays a weak affinity for the m and d-opioid receptors, and weaker affinity for the k-subtype; it also interferes with the neuronal release and reuptake of serotonin and noradrenaline in the descending inhibitory pathways. The metabolism of this drug has been investigated in different animals (rats, mice, Syrian hamsters, guinea pigs, rabbits, and dogs) and humans; similar metabolites are produced but in different amounts. The major metabolic pathways involved in phase I metabolite production (M1M5) are O-demethylation, N-demethylation, and N,N-demethylation. The aim of the current study is to evaluate the pharmacokinetic profile of T in the horse, and its M1, M2, and M5 metabolites after single-dose administration (5 mg/kg body weight [BW]) by intravenous, sustained-release tablets and immediate- release capsules. We also will investigate the potential effects of fasting and feeding on bioavailability of immediate-release capsules. The study design was divided into four randomized phases. Twenty-four gelding Italian trotter race horses were divided into four groups (6 animals each) and administered T intravenously, with T immediate-release capsules in a fasting status, T immediate-release capsules in a feeding status, and T sustained-release in fasting status. Blood samples were collected at different times and analyzed by highpressure liquid chromatography (HPLC) with fluorimetric detection. The limit of quantification was 5 ng/ml for T, M1, and M2, and 10 ng/ml for M5. A one-compartment model best fit the plasma concentrations of T and M2 after all treatments. Unfortunately, for M1 and M5, it was not always possible to fit plasma curves because of very low and variable concentrations. M2 was the main metabolite produced in the four different treatments and its concentration was higher than the concentration of T after sustained-release administration. Conversely, M1, the main metabolite in humans, and M5 seemed to be only marginally produced in the horse. When T was administered in both fasted and fed states, variations in some pharmacokinetic parameters were not considered clinically significant. We concluded that T could be administered in either a fasted or a fed condition

N-(Indol-3-ylglyoxylyl)methionine derivatives: preparation and gastric anti-secretory activity.

The authors describe the synthesis of several N-(indol-3-ylglyoxylyl)methionine derivatives. The target compounds were prepared starting from substituted indoleglyoxylyl chlorides and methionine ethyl ester. Some of them were tested for their gastric anti-secretory activity. Among these compounds, the N-(5-chloroindol-3-ylglyoxylyl)methionine Ve was the most active, being quite comparable to cimetidine

Stereoselective synthesis and beta-blocking activity of substituted (E)- and (Z)-4(1H)-[1-(3-alkylamino-2-hydroxypropyl)oximino]-2,3-dihydro-1,8-naphthyridine. Potential antihypertensive” agents. Part VI

The synthesis of R-(+)- and S-(-)-isomers of substituted (E)- and (Z)-4(1H)-[1-(3-alkylamino-2-hydroxypropyl)-oximino]-2,3-dihydro-1,8-naphthyridine, in enantiomeric pure form, is described. These compounds showed an interesting beta-blocking activity. Generally, the (S)-enantiomers possess a slighthly higher affinity for beta receptors than the (R)-enantiomers

An unexpected result in the condensation of 2-amino-6-bromo-pyridine with ethyl 4-chloroacetoacetate: four dihalo-substituted pyrido[1,2-a]pyrimidin-4-ones as reaction products

We report here the condensation of 2-amino-6-bromopyridine with ethyl 4-chloroacetoacetate in polyphosphoric acid. In this reaction, a mixture of the four possible dihalo-4H-pyrido[1,2-a]pyrimidin-4-ones 1-4 was obtained