Studies on antifungal agents. In vitro activity of novel cis-5-alkoxy (or acyloxy)alkyl-3-phenyl-3-(1H-imidazol-1-ylmethyl)-2-methylisoxazolidine derivatives.

The synthesis and in vitro antifungal activity of a novel series of cis-5-alkoxy(or acyloxy)alkyl-3-phenyl-3-(1H-imidazol-1-ylmethyl)- 2-methylisoxazolidine derivatives (6a-n) are described. The 5-[(4-chlorobenzyloxy)methyl] analogue 6h and the two 5-acyloxymethyl derivatives 6k,l demonstrated the best overall potency. Against Candida stellatoidea, the minimum inhibitory concentrations (MIC's) for 6h,k,l ranged between 0.

Effect of oxamisole on immune parameters of mice infected with murine hepatitis.

The effects of Oxamisole, 2,3,5,6,7,8-hexahydro-2-phenyl-8,8- dimethoxyimidazo[1,2a]pyridine on immune parameters of mice infected with murine hepatitis were investigated. Young Swiss Webster mice were injected intraperitoneally (i.p.

Flavodilol: a new antihypertensive agent that preferentially depletes peripheral biogenic amines.

Flavodilol, ((+/-)-7-[2-hydroxy-3-(propylamine)-propoxy]flavone maleate), a new orally effective antihypertensive agent, extensively depleted catecholamines and serotonin in heart tissue of normotensive and spontaneously hypertensive rats (SHR). Dose-response studies demonstrated that greater than or equal to 75% depletion of cardiac norepinephrine (NE) was accompanied by marked blood pressure decline in SHR. In contrast, whole brain biogenic amine levels were decreased only by 15-20% after acute or chronic treatment with antihypertensive doses (35-75 mg/kg).

Flavodilol: a new antihypertensive agent.

Flavodilol, a new antihypertensive drug, was evaluated in a variety of test systems for better understanding of its biologic properties and the nature of its mechanism of action. Oral administration of the drug to spontaneously hypertensive rats (SHR) lowered arterial blood pressure (ABP) in a dose-related manner, and doses greater than 35 mg/kg increased duration but not magnitude of the response. In contrast, oral administration of flavodilol to normotensive rats did not significantly alter ABP at 35 mg/kg, although larger doses of 75 or 150 mg/kg significantly lowered ABP.

Selection of orally active antifungal agents from 3,5-substituted isoxazolidine derivatives based on acute efficacy-safety profiles.

Routine in vitro screening of a new synthetic series of 3,5-substituted 2-methylisoxazolidines revealed that three imidazole analogs (PR 967-248, PR 967-234, and PR 969-566) and, to a lesser extent, a triazole analog (PR 988-399) exerted rather potent antifungal activity against three systemic and four dermatophytic classes of fungi. When tested in vivo for ability to eradicate Candida vaginitis in the rat, the triazole derivative, PR 988-399, was effective after oral administration. In this in vivo test for efficacy, PR 967-234 and PR 969-566 reduced but did not eradicate the infection, while PR 967-248 was inactive.