Romazarit: a potential disease-modifying antirheumatic drug.

The synthesis of a series of substituted heterocyclic alkoxypropionic acids is described. They were evaluated for antiinflammatory effects in two animal models of chronic inflammation; adjuvant arthritis and type II collagen arthritis in the rat. The desired profile of biological activity was characterized by the reduction of inflammation with the coincident restoration toward normal levels of the biochemical markers (acute phase proteins) associated with the inflammatory response, an effect that was not shared by classical nonsteroidal antiinflammatory agents.

Lack of stereoselectivity in the pharmacokinetics and metabolism of the radiosensitizer Ro 03-8799 in man.

During a clinical toxicity study it was possible to obtain urine samples from six patients receiving either the R-(-)- or S-(+)-stereoenantiomeric forms of the developmental 2-nitroimidazole radiosensitizer Ro 03-8799 (pimonidazole). Paired plasma samples were also obtained from four patients. The pharmacokinetic data were compared with those for the racemic mixture in the same individuals.

A comparative study of Ro 03-8799: racemic mixture and enantiomers.

The maximum single dose of the 2-nitroimidazole hypoxic cell radiosensitiser Ro 03-8799 is limited to 1 g/m2 by the occurrence of a well characterised acute syndrome of sweating, nausea and mental changes. In an attempt to increase the tolerable dose, the clinical toxicity of the racemic mixture was compared with that of the R- and S-enantiomers of Ro 03-8799. Twelve patients received escalating alternate doses of racemic mixture and R- or S-enantiomer, the dose levels being 0.

Polyfunctional radiosensitizers. VII. Radiosensitization by conformationally-restricted isomers of a nitroxyl biradical in vitro.

Bothtrans-N,N'-bis(2,2,6,6-tetramethyl-1-oxyl-4-piperidinyl)-1, 2-diaminocyclopropane[Ro31-2269] and its cis isomer [Ro 31-2778] selectively sensitized hypoxic Chinese hamster cells, line V-79-753B, to radiation by decreasing both the D0 value and extrapolation number, whereas a related dibasic monoradical Ro 31-2655 decreased D0 alone. Although sensitization was maximal after a 1-hr cell-drug contact time, cells continued to accumulate both Ro 31-2269 and Ro 31-2778 when this contact time was increased up to 3 hr. There was no evidence for competition between either biradical and 2,2,6,6-tetramethyl-4-piperidinol-N-oxyl (TMPN) at equimolar concentration or biradical and 0.