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, p.o., inhibited degradation of articular cartilage in a rat monoarthritis model induced by an intra-articular injection of Propionibacterium acnes. 6 Ro 32-3555 is a potential therapy for the treatment of the chronic destruction of articulating cartilage in both rheumatoid and osteoarthritis.

We report the cytotoxicity toward B16 cells and antitumor activity in three transplantable tumor models of a series of ionic, tetrahedral, bischelated gold diphosphine complexes of the type [Au1(R2PYPR2')2]X, where Y = (CH2)2, (CH2)3, or cis-CH = CH. The anion (X = Cl, Br, I, CH3SO3, NO3, PF6) had little effect upon activity. The R = R' = phenyl complexes 1, 7, and 8 [Y = (CH2)2, (CH2)3, cis-CH = CH, X = Cl] were the most active against P388 leukemia, with an increase in lifespan ranging from 83 to 92% and were also active against M5076 sarcoma and B16 melanoma. Complexes with pyridyl or fluorophenyl substituents had reduced activities. For the latter, 19F and 31P NMR were used to verify the formation of bischelated gold(I) complexes in solution. The reduced activity of the complex with R = Et and R' = Ph and inactivity with R = R' = Et are discussed in terms of their increased reactivity as reducing agents. 31P NMR studies show that [AuI(Et2P(CH2)2PPh2)2]Cl readily reacts with serum, albumin, and Cu2+ ions to give oxidized ligand.

a new gold comp oundfortreating rheumatoid arthritis (RA), is unique in that itproduces its therapeutic benefit when administered by the oral route. Currently used gold preparations (sodium aurothiomalate, aurothioglucose) must be given by injection to be effective. Auranofin has been used in the treatment of RA patients in clinical trials, and is comparable in efficacy to presently used injectable agents. Side effects with auranofin are mild in, nature and result in fewer withdrawals from therapy than do injectable gold preparations.

identified (IR spectrum, melting point) as the original Co cluster catalyst. An immobile green material, which was not identified, always was present on top of the silicic acid pad.Table I summarizes the experimental details of the catalysis experiments.Infrared Studies of Hydroformylation Reaction Mixtures. In these experiments, the cooled and depressurized reactor was opened to a nitrogen atmosphere in the drybox, and a sample of the reaction mixture was placed in a 0.1-mm path length NaCl solution cell and sealed from the atmosphere. An IR spectrum was recorded of the v(CmO) region (2150-1800 cm"1) with a Perkin-Elmer 180 grating infrared spectrophotometer using toluene as the reference solvent. IR spectra also were recorded for pure PhCCo3(CO)9 and Co2(CO)8.Table II summarizes these IR data.

1. The metabolism of mibefradil has been examined in rat, marmoset, cynomolgus monkey and man after single and multiple oral administration. 2. Metabolites typically represent between 50 and 80% of the circulating drug-related material after single oral doses of mibefradil to man, rat and marmoset. They arise by a combination of enzymatic processes: cytochrome P450-mediated oxidation at saturated and unsaturated carbon atoms, cytochrome P450-catalysed dealkylation and hydrolysis of the ester side-chain. 3. Plasma levels of mibefradil in the cynomolgus monkey are extremely low as a result of very efficient first-pass hydrolysis of its side-chain to give the corresponding alcohol. Steady-state concentrations of this metabolite are comparable with those of the parent drug in man and marmoset, but are relatively low in rat plasma. 4. Hydroxylation at the benzylic carbon of the tetrahydronaphthyl ring leads to further important metabolites in primates, whereas the products of O- and N-demethylation are found in small amounts in all four species. 5. Estimates of the exposure of the various species to the principal metabolites indicate that the choice of the rat, marmoset and cynomolgus monkey for the toxicological assessment of mibefradil was appropriate.

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