RESUMO
As a continuation of our goals to study molecular probes for muscarinic cholinergic receptors, a series of 3-substituted 2-methyl-2-phenylpropanoates with the general structure of C6H5C(CH2X)(CH3)COOCH2CH2NEt2 where X = OH, OTs, F, Cl, Br, I, and OAc were prepared and their antispasmodic activities examined on isolated rat ileum preparations. Structure-activity relationship studies with these compounds provide further evidence suggesting that binding of an aromatic moiety in a specific location within the hydrophobic region of the receptor is important for anticholinergic potency. A nucleophilic displacement of chloride by "naked" fluoride under mild conditions is also reported.
Assuntos
Parassimpatolíticos/síntese química , Fenilpropionatos/síntese química , Receptores Muscarínicos/metabolismo , Animais , Ésteres/síntese química , Ésteres/farmacologia , Etanolaminas/síntese química , Etanolaminas/farmacologia , Técnicas In Vitro , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , Fenilpropionatos/farmacologia , Ratos , Ratos Endogâmicos , Receptores Muscarínicos/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Two series of compounds having the general structure of C6H5CRR'COOCH2CH2NEt2 were synthesized and examined for their antispasmodic activities. These compounds were selected as structural probes for exploring the nature of muscarinic cholinergic receptor binding sites that interact with atropine-like anticholinergics. These studies indicate a rather strict size limitation for the hydrophobic region of the receptor and suggest intramolecular hydrogen bonding as a possible means to explain the observed stereoselectivity.
Assuntos
Parassimpatolíticos/síntese química , Fenilacetatos/síntese química , Receptores Muscarínicos/metabolismo , Alquilação , Animais , Ésteres/síntese química , Ésteres/farmacologia , Etanolaminas/síntese química , Etanolaminas/farmacologia , Indicadores e Reagentes , Cinética , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , Fenilacetatos/farmacologia , Ratos , Ratos Endogâmicos , Receptores Muscarínicos/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
A reinvestigation of the constituents of the Osage orange (maclura pomifera) yielded, in addition to the previously reported triterpenses (lupeol, butyrospermol, and lupan-3beta,20-diol), the pigments osajin and pomiferin, and a previously unreported constituent. The structure of this new compound was investigated. On the basis of spectroscopic and chemical data, it appeared to be an epimer of lupeol and is referred to as 19alpha-H-lupeol.
Assuntos
Plantas Medicinais/análise , Triterpenos/isolamento & purificação , Acetilação , Álcoois/isolamento & purificação , Hidrólise , Espectroscopia de Ressonância Magnética , Conformação Molecular , Ozônio , Triterpenos Pentacíclicos , Pigmentos Biológicos/isolamento & purificação , Espectrofotometria InfravermelhoRESUMO
A complex of phenobarbital and ephedrine was prepared and characterized. The complex was differentiated from physical mixtures of the two drugs by TLC and IR spectroscopy. NMR spectroscopy was used to verify the proportion of each drug in the complex and to confirm the existence of intermolecular binding. Mass spectrometry was employed to establish that all fragments characteristic of the individual drug entities could be isolated from the complex. Elemental analysis confirmed the chemical composition of the complex. A possible chemical structure for the complex was hypothesized on the basis of the chemical and spectroscopic data.
Assuntos
Efedrina/análise , Fenobarbital/análise , Fenômenos Químicos , Química , Cromatografia em Camada Fina , Espectroscopia de Ressonância Magnética , Espectrofotometria InfravermelhoRESUMO
Isomers of the 2- and 9-aminobenzonorbornenes were prepared as rigid analogs of amphetamine and were employed to study the conformational requirements of indirectly acting sympathomimetic agents. Of this series of isomeric amines, the exo-2 and anti-9 isomers closely resemble the fully extended conformation of amphetamine. The other two amines, the endo-2 and syn-9 isomers, conformationally resemble the folded conformation of amphetamine. The isomers that resemble the extended conformation of amphetamine increased the spontaneous motor activity in mice while the isomers resembling the folded form either decreased or had no effect on motor activity. These compounds also were studied for their ability to accelerate the efflux of tritiated norepinephrine from vesicular and nonvesicular storage sites of isolated perfused rabbit atria; either alpha-methyl-p-tyrosine- or reserpine-pretreated rabbits were used. Amphetamine and the exo-2 and anti-9 isomers of aminobenzonorbornene could accelerate norepinephrine efflux from either compartment while the endo-2 and syn-9 isomers could accelerate the efflux from only the nonvesicular compartment at the concentrations studied. Fenfluramine and methylphenidate also were studied for their ability to accelerate efflux. Fenfluramine and methylphenidate resembled the aminobenzonorbornenes that correspond to the folded conformation of amphetamine in their ability to accelerate the efflux from nonvesicular storage. However, fenfluramine also resembled amphetamine and the aminobenzonorbornenes corresponding to the extended conformation of amphetamine in its ability to accelerate efflux from vesicular storage sites. The response to methylphenidate was similar to that of the aminobenzonorbornenes resembling the folded conformation of amphetamine.