RESUMO
A number of oxamic acid derivatives of tropones and tropolones were synthesized and their antianaphylactic activity was determined in passive paw anaphylaxis (PPA). Several of these esters possessed oral activity. A comparison of the effect on the biological activity of the esters and the corresponding acid and its salt is reported. The experiments suggesting a relationship between the activity and the bioavailability of the ester 19 are also described. A study of the fate of ester 19 in serum on oral or intravenous administration to rats and dogs is reported. In vitro results of the effect of the compounds 19, 45, and 45a on the activity of the guinea pig lung and beef heart phosphodiesterase are presented. The various factors that may contribute to the antiallergy activity of compounds of this series are discussed.
Assuntos
Aminoácidos/análogos & derivados , Cicloeptanos/síntese química , Ácido Oxâmico/análogos & derivados , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Tropolona/síntese química , 3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Adenilil Ciclases/metabolismo , Animais , Bovinos , Cães , Cobaias , Técnicas In Vitro , Pulmão/enzimologia , Camundongos , Ácido Oxâmico/síntese química , Relação Estrutura-Atividade , Fatores de Tempo , Tropolona/análogos & derivadosRESUMO
Two analogues of human insulin, des(tetrapeptide B(1-4))-and des (pentapeptide B(1-5))-insulin, which differ from the parent molecule in that the N-terminal tetrapeptide and pentapeptide sequences, respectively, have been eliminated, have been synthesized. The des(tetrapeptide B(1-4))-insulin shows potencies of 13 IU/mg by the mouse convulsion assay method and 7.6 IU/mg by the radioimmunoassay method. The des(pentapeptide B(1-5))-insulin possesses a potency of 1.2 IU/mg when assayed by the glucose-oxidation method in isolated fat cells and 3.7 IU/mg by the radioimmunoassay technique. The natural hormone has a potency of 23--25 IU/mg by both assay methods.
