RESUMO
m- and p-aminobenzoic acids were converted to the title compounds by sequential use of ClCH2COCl, SOCl2, glycine methyl or ethyl ester, AcSK, and hydrolysis. The title compounds and a number of salts were compared for mucolytic activity, toxicity, stability, and hygroscopicity. When compared to N-acetyl-L-cysteine (NAC), the compounds exhibit several times the in vitro mucolytic activity of NAC on a molar basis. The most promising candidate appears to be the sodium salt 3.5H2O 2 of the meta series.
Assuntos
Aminobenzoatos/síntese química , Expectorantes , Glicina/análogos & derivados , Acetilcisteína/farmacologia , Aminobenzoatos/farmacologia , Aminobenzoatos/toxicidade , Animais , Fenômenos Químicos , Química , Estabilidade de Medicamentos , Glicina/síntese química , Glicina/farmacologia , Glicina/toxicidade , Humanos , Isomerismo , Dose Letal Mediana , Camundongos , Muco/efeitos dos fármacos , Ratos , Sais , Escarro/efeitos dos fármacos , ÁguaRESUMO
A series of 25 aryloxypropanolamines containing the 3-indolyl-tert-butyl [i.e., 1,1-dimethyl-2-(1H-indol-3-yl)ethyl] or substituted 3-indolyl-tert-butyl moiety as the N substituent is reported. These compounds have been tested for antihypertensive activity in spontaneously hypertensive rats (SHR), beta-adrenergic receptor antagonist action in conscious normotensive rats, vasodilating activity in ganglion-blocked rats with blood pressure maintained by angiotensin II infusion, and for intrinsic sympathomimetic action (ISA) in reserpinized rats. Some of the compounds exhibit antihypertensive activity in combination with beta adrenergic receptor antagonist and vasodilating action. The structure--activity relationships in these tests are discussed.
Assuntos
Antagonistas Adrenérgicos beta/síntese química , Anti-Hipertensivos/síntese química , Propanolaminas/síntese química , Vasodilatadores/síntese química , Animais , Hipertensão/fisiopatologia , Indóis/síntese química , Indóis/farmacologia , Masculino , Propanolaminas/farmacologia , Ratos , Relação Estrutura-Atividade , Simpatomiméticos/síntese químicaRESUMO
The central nervous system (CNS) activities of a number of soterenol analogs have been investigated, and several of these compounds possessed potent morphine antagonistic and anorexiant properties. The CNS activity of these compounds was enhanced by certain lipophilic [e.g., 1,1-dimethyl-2-phenethyl (43) or cyclopropyl (40 and 44)] nitrogen substituents; however, minor structural changes on either the aromatic or side-chain moieties drastically reduced central activity. Toxicity in this series was related to the inherent alpha-adrenergic stimulating component (direct or indirect).
