RESUMO
A series of 14 vinylureidopenicillins and a series of 9 ureidopenicillins were prepared by reaction of 6-aminopenicillanic acid with vinyl isocyanates and isocyanates. These compounds were evaluated for their potential to protect ruminants against lactic acidosis. The compounds were tested for inhibition of in vitro ruminal lactic and propionic acid production, and six compounds inhibited lactic acid production to less than 10% of control at doses of 0.31 microgram/mL or lower, whereas they did not inhibit propionic acid production at doses greater than 10 micrograms/mL. The most active compounds also were screened for general antibacterial activity and were found to be weakly active against Gram-positive bacteria. The structure--activity relationships are discussed for both series. Triethylammonium 6-[3[2-(4-tert-butylphenyl)vinyl]ureido]penicillanate (4) was chosen for evaluation as an inhibitor of intraruminal lactic acidosis in vivo.
Assuntos
Antibacterianos/farmacologia , Lactatos/biossíntese , Penicilinas/farmacologia , Rúmen/metabolismo , Acidose/prevenção & controle , Animais , Antibacterianos/síntese química , Bactérias/efeitos dos fármacos , Bovinos , Ácido Láctico , Penicilinas/síntese química , Relação Estrutura-Atividade , Ureia/análogos & derivados , Ureia/síntese química , Ureia/farmacologia , Compostos de Vinila/síntese química , Compostos de Vinila/farmacologiaRESUMO
The syntheses of 44 5H-dibenzo[a,d]cyclohepten-5-one derivatives bearing a carboxyl gropu at the 1, 2, 3, or 10 position and various substituents at the 7, 8, or 9 position are described. Some of the compounds showed significant bronchodilator activity in guinea pigs and protected the animals against a histamine challenge administered either by aerosol or intravenously. The most active compounds were 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one-2-carboxylic acids bearing a methyl or halogen substituent at the 9 position. These compounds were approximately as active as aminophylline by intraperitoneal administration.
Assuntos
Broncodilatadores/síntese química , Ácidos Carboxílicos/síntese química , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Ácidos Carboxílicos/farmacologia , Feminino , Cobaias , Antagonistas dos Receptores Histamínicos , Técnicas In Vitro , Relação Estrutura-Atividade , Traqueia/efeitos dos fármacosRESUMO
A series of xanthone-2-carboxylic acids, substituted mainly with electron-withdrawing groups, has been synthesized and assayed for antiallergic activity, using the passive cutaneous anaphylaxis (PCA) reaction in the rat. The effect of substituent type and substitution pattern on PCA neutralizing capacity is presented.
Assuntos
Hipersensibilidade/tratamento farmacológico , Xantinas/síntese química , Animais , Feminino , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Ratos , Relação Estrutura-Atividade , Xantinas/farmacologiaRESUMO
A series of para-substituted N-(beta-styryl)formamides, analogues of tuberin (4a), has been prepared and assayed for antibacterial activity. The methylthio, ethoxy, and methyl analogues 4e, 4j, and 4t were about twice as active as tuberin against Mycobacterium phlei. Although tuberin lacks activity against Staphylococcus aureus, several of the analogues described were found to inhibit this organism. The phenyl group of tuberin is not a prerequisite for activity since analogues based on naphthyl or ferrocenyl groups were also active. A quantitative structure-activity relationship further implied that an aromatic group need not be present, suggesting the synthesis of the cyclohexyl and n-amyl analogues which were found to possess high activity.
