Gastric antisecretory, antiulcer and cytoprotective properties of 9-hydroxy-19,20-bis-nor-prostanoic acid in experimental animals.

9-Hydroxy-19,20-bis-nor-prostanoic acid (IBI-C83) was evaluated on gastric acid secretion and gastric lesions induced in laboratory animals by a variety of experimental conditions: compound IBI-C83 is proved effective in decreasing basal, histamine- and pentagastrin-stimulated total acid output in rats and in pentagastrin perfused dogs. The concentration of N-acetylneuraminic acid in the gastric fluid, a marker of mucus secretion, is enhanced in rats by IBI-C83. This drug prevents gastric damage induced by non-steroidal antiinflammatory compounds such as acetylsalicylic acid, indometacin and phenylbutazone, gastric ulcers following pylorus ligation, and facilitates healing of the gastric ulcers evoked by subserosal injection of acetic acid. A prominent feature of IBI-C83 is its capacity to protect the rat from gastric damage elicited by necrotizing agents such as absolute ethanol, hydrochloric acid and hypertonic saline. This property, called "cytoprotection" and common to naturally occuring prostaglandins, is independent on the antisecretory activity of IBI-C83 and is not shared, at least in the reported experimental models, by the H2-receptor antagonist cimetidine. In spite of the prostaglandin-like properties displayed in its cytoprotective activity, compound IBI-C83 does not affect cardiovascular functions, gastrointestinal transit and uterine motility.

Synthesis and biological activity of digitoxigenin aminoesters.

A series of 3 beta-esters of digitoxigenin (3 beta-hydroxy-14 beta-hydroxy-5 beta-card-20(22)-enolide) with alpha-aminoacids, were synthesized and tested for inotropic activity on the guinea-pig isolated heart and by slow infusion in the cat in comparison with digitoxigenin, Lanatoside C and Strophantin K. Esterification of the 3 beta-hydroxy group of digitoxigenin with various amino acids led to compounds still retaining inotropic activity with low in vivo potency and short duration of action. The compounds are inactive when administered orally.

Chemical modifications in the tetracycline series.

New tetracycline analogs modified at position 5, 6 and 2 were synthetized. The 5-deoxy-5-oxo-derivatives, 2a and 3a, were obtained by DMSO/acetic anhydride oxidation of doxycycline (2) and methacycline (3), respectively; the 6-demethyl-6-hydroxymethyl-6-alpha-hydroxyoxytetracycline (3b) by methacycline oxidation with the KCIO3/OsO4 system and the 6-hydroxyanhydrooxytetracycline (4) treating 3b with periodic acid. The 2-ethoxycarbonyl-2-decarboxamidodoxycycline (2b), was synthesized by treating doxycycline nitrile (2c) with EtOH and anhydrous HCl, 2-thiocarboxamide-2-decarboxamidodoxycycline (2d) by reaction of doxycycline with P2S5 in dioxane and 2-aminomethyl-2-decarboxamidodoxycycline (2e) by RANEY-Nickel reduction of 2d. All the synthetized compounds proved to be almost inactive on agar plates both on Gram-positive and Gram-negative bacteria.

Synthesis and antibacterial activity of some ureido cephalexin and cefadroxil derivatives.

The antibacterial activity of some ureido, acylureido and carbamoylureido derivatives of cephalexin and cefadroxil, prepared in our laboratories, as compared to parent compounds is reported. Only the 7-[D-alpha-(imidazolidin-2-one-1-ylcarbonylamino)-alpha-phenylacetamido]-3-methyl-3-cephem-4-carboxylic acid (IV d) and the 7-[D-alpha-(imidazolidin-2-one-1-ylcarbonylamino)-alpha-p-hydroxyphenylacetamido]-3-methyl-3-cephem-4-carboxylic acid (V c) showed some antibiotic activity. However we found no activity improvement against Pseudomonas strains (contrary to the results obtained in similar penicillin derivatives) and a lower beta-lactamase resistance.

Metabolic pathway of the diethylamide of trans-3-methyl-4-phenyl-3-butenoic acid, an hypolipemic agent, in the rabbit.

The metabolism of the hypolipemic agent 3-methyl-4-phenyl-3-butenoic acid diethylamide (I) after oral administration to rabbits has been qualitatively investigated. Four main metabolites were identified in the urine of animals deriving from three different metabolic processes: aromatic hydroxylation, lactonization and N-dealkylation. All metabolites occured in free forms, were pharmacologically inactive and the unchanged starting drug was never recovered. The metabolic pathway of compound I was also compared with that of the parent non-substituted amide, 3-methyl-4-phenyl-3-butenamide (II). The fate of the two structurally related drugs was similar, except for hydroxylation of the carbon in the alpha position to the amidic group, occuring in compound II but not in compound I.