Disease modifying activity of HWA 486 in rat adjuvant-induced arthritis.

HWA 486 was investigated for its ability to modify the development of adjuvant-induced polyarthritis in Lewis rats. HWA 486 (20 mg/kg/day p.o.

Immunotherapy of Madison 109 lung carcinoma and other murine tumors using lentinan.

Lentinan was evaluated initially against the Lewis (LL) and Madison 109 (M109) lung carcinomas implanted in the footpads of syngeneic mice. Activity in these tumor models was assessed by both reduction in early tumor growth rates and increases in life span and cures, relative to untreated control mice with tumors. Lentinan given i.

BL-5255 II: effects on release and smooth muscle activity of mediators of immediate hypersensitivity reactions.

BL-5255 inhibited release of preformed mediators from passively sensitized mast cells in the rat peritoneal cavity, chopped monkey lung or human lung tissue. The compound failed to block rat cutaneous reactions elicited by histamine or serotonin. It exhibited weak to no ability, depending on the mediator employed, to block contraction of isolated guinea pig ileum or tracheal tissue.

BL-5255. I. Activity in animal models of immediate hypersensitivity reactions.

BL-5255 exhibited potent activity in several models of antigen-induced immediate hypersensitivity reactions in rats and guinea pigs. The compound was effective whether administered by oral or parenteral routes and in passively and actively sensitized animals. It appeared to be readily absorbed when given orally.

BL-5255, a tetrazolylpyrimidinone with potent oral antiallergy activity in animals.

BL-5255, 2-(2-n-propoxyphenyl)-5-(5-1 H-tetrazolyl)pyrimidin-4 (3H)-one, effectively inhibited allergic reactions in sensitized rats or guinea pigs when administered by oral or intravenous routes as the water-soluble sodium or ethanolamine monohydrate salts. In the IgE-mediated rat PCA, BL-5255 was 50 times more potent than disodium cromoglycate by intravenous administration. When administered orally in this model, BL-5255 inhibited the PCA reaction by 50% at 0.

Stimulation of interferon production in mice and in mouse spleen leukocytes by analogues of BL-20803.

Various structural analogues of the interferon inducer BL-20803 exhibited close agreement between ability to stimulate interferon production in the intact mouse and in cultures of spleen adherent leukocytes.

Target cells for interferon induction by BL-20803.

The role of certain cells of the reticuloendothelial system in the interferon response of mice to the low-molecular-weight compound 1,3-dimethyl-4-(3-dimethylaminopropylamino)-1H-pyrazola-3,4-b-quinoline dihydrochloride (BL-20803) was studied. Mouse spleen adherent cells cultured in vitro with subtoxic concentrations of BL-20803 produced interferon. Adherent cells isolated from peritoneal washes were unresponsive to the compound.

Interferon inducing activities of derivatives of 1,3-dimethyl-4-(3-dimethylaminopropylamino)-1H-pyrazolo(3,4-b)quinoline and related compounds.

Syntheses and interferon inducing acitivites are reported for 137 relatives of 1,3-dimethyl-4-(3-dimethylamino-propylamino)-1H-pyrazolo[3,4-b]quinoline (1). Three different generalized synthetic schemes for the preparation of pyrazolo[3,4-b]quinolines are presented and limitations contrasted. Other heterocyclic nuclei containing the 3-dimethylaminopropylamino side chain include pyridine, quinoline, acridine, pyrazolo[3,4-b]pyridine, pyrazolo[3,4-B][1,8]naphthyridine, pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine, dipyrazolo[3,4-b:4',3'-e]pyridine, pyrrolo-[2,3-b]quinoline, isothiazolo[5,4-b]quinoline, and pyrido[2,3-h]pyrazolo[3,4-b]quinoline.

In vivo and in vitro stimulation of mouse spleen leukocytes by BL-20803, a low-molecular-weight interferon inducer.

BL-20803, a low-molecular-weight compound, although able to elicit circulating interferon in the mouse, failed to protect cultured cell lines in vitro from infection by interferon-sensitive viruses. Of the tissues analyzed for interferon content after oral administration of the drug to mice, spleen and lung contained the largest amounts of the virus inhibitor. Spleen cells from such dosed animals when isolated into in vitro cultures elaborated small amounts of interferon into the culture medium.

BL-20803, a new, low-molecular-weight interferon inducer.

BL-20803 induced interferon in mice when administered via oral or parenteral routes. During multiple dosing with the drug at 48-h intervals, animals exhibited a hyporesponsive state to the third treatment. Inhibition of vaccinia virus infection was correlated with interferon induction.