RESUMO
Analogues of farnesyl pyrophosphate containing a farnesyl moiety and a variety of amine residues replacing the pyrophosphate have been synthesized. Most of these compounds were effective inhibitors of the synthesis of squalene and presqualene pyrophosphate from farnesyl pyrophosphate. 50% inhibition was obtained at concentrations between 50 and 100 micron. These analogues also inhibited other microsomal enzymes so they apparently function as general inhibitors of microsomal enzymes.
Assuntos
Farneseno Álcool/análogos & derivados , Fosfatos de Poli-Isoprenil/farmacologia , Saccharomyces cerevisiae/metabolismo , Esqualeno/biossíntese , Redutases do Citocromo/antagonistas & inibidores , Farneseno Álcool/farmacologia , Glucose-6-Fosfatase/antagonistas & inibidores , Isomerases/metabolismo , Lanosterol , Microssomos/efeitos dos fármacos , Microssomos/enzimologia , Microssomos/metabolismo , Esqualeno/análogos & derivados , Relação Estrutura-AtividadeRESUMO
(-)-Alprenolol is a potent competitive beta-adrenergic antagonist. "(-)-[3H]Alprenolol", a radioactive form of this agent produced by catalytic reduction with tritium, has recently been used successfully as a radioligand for direct studies of beta-adrenergic receptors. In this communication it is documented that the compound formed by catalytic reduction of (-)-alprenolol with tritium gas is the saturated product (-)-[3H]dihydroalprenolol in which tritium is added across the double bond and exchanged into the adjacent benzylic position. No exchange into the aromatic ring was observed. These conclusions were substantiated by results obtained on hydrogenation and deuteration of (-)-alprenolol. The biological activity of (-)-[3H]dihydroalprenolol, dihydroalprenolol, and alprenolol was also shown to be identical as assessed by direct ligand binding and inhibition of catecholamine-stimulated adenylate cyclase.
Assuntos
Alprenolol/análogos & derivados , Receptores Adrenérgicos beta/efeitos dos fármacos , Receptores Adrenérgicos/efeitos dos fármacos , Inibidores de Adenilil Ciclases , Adenilil Ciclases/sangue , Alprenolol/sangue , Alprenolol/farmacologia , Animais , Anuros , Fenômenos Químicos , Química , Membrana Eritrocítica/enzimologia , Membrana Eritrocítica/metabolismo , Hidrogenação , Técnicas In Vitro , Ligantes , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Relação Estrutura-Atividade , TrítioRESUMO
The distribution of tritium atoms in some labeled steroids has been determined by tritium nuclear magnetic resonance spectroscopy. In addition, the distribution of molecular types (mono vs. polytritiated) and nuclear Overhauser enhancements have been determined. As near maximal NOE's were observed, quantitative distribution information was derived from NOE suppressed spectra.
