Search PubMed⌕ Search

Biomedical subjects

T J Ward

Publications and source records attributed to T J Ward.

25 records · Page 2Linked to original sources
PubMed1988

Synthesis and structure-activity relationships of 2-sulfonamido-1,3,4,6,7,11b alpha-hexahydro-2H-benzo[a]quinolizines as alpha 2-adrenoceptor antagonists.

A series of 2-sulfonamido-1,3,4,6,7,11b alpha-hexahydro-2H-benzo[a]quinolizines were synthesized and examined for alpha 2- and alpha 1-adrenoceptor antagonist activity on the rat vas deferens and anococcygeus muscle, respectively. A number of compounds in this series were shown to be potent and selective alpha 2-adrenoceptor antagonists. Studies on the resolved enantiomers of compounds 6, 10, and 16 showed that alpha 2-adrenoceptor antagonist activity resided primarily in the 2R,11bS isomers, related to the absolute configuration of the alpha 2-antagonist yohimbine, such that the benzene ring and sulfonamide groups in this series were superimposable on the pyrrole and ester groups of yohimbine.

Animals↗
PubMed1986

Separation of drug stereoisomers by the formation of beta-cyclodextrin inclusion complexes.

For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized beta-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as beta-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of beta-cyclodextrin complexes of propanolol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of beta-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiomeric drugs.

Chemical Phenomena↗
PubMed1985

Synthesis and antidiarrheal activity of N-(aminoiminomethyl)-1H-pyrrole-1-acetamides related to guanfacine.

A series of N-(aminoiminomethyl)-1H-pyrrole-1-acetamides, related to guanfacine, were prepared and tested for antidiarrheal activity in castor oil dosed rats. trans-N-(Aminoiminomethyl)-2,5-dihydro-2,5-dimethyl-1H-pyrrole-1-acetami de (2), in which the dichlorophenyl ring of guanfacine is replaced by 2,5-dimethyl-2,5-dihydropyrrole, showed potent antidiarrheal activity but possessed only minimal cardiovascular activity in rats.

Animals↗
PubMed1980

Antihypertensive ureidopiperidines.

The synthesis of a series of 1-aralkyl-4-ureidopiperidines is reported. These compounds are related to the benzamidopiperidines exemplified by indoramin. Some of the ureidopiperidines are more potent antihypertensive agents than their benzamidopiperidine counterparts. Two examples, 1-(2-thenoyl)-3-[1-[2-(3-indolyl)ethyl]piperid-4-yl]urea and 1-(2-thenoyl)-3-[1-[4-(4-fluorophenyl)-4-oxobutyl]piperid-4-yl]urea (19 and 58), emerged as the most potent antihypertensive agents in this series.

Animals↗