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Biomedical subjects

J D Albright

Publications and source records attributed to J D Albright.

11 recordsLinked to original sources
PubMed1983

Antihypertensive agents: angiotensin converting enzyme inhibitors. 1-[3-(Acylthio)-3-aroylpropionyl]-L-prolines.

A series of 1-[3-(acylthio)-3-aroylpropionyl]-L-proline derivatives was synthesized. A number of these compounds are potent angiotensin converting enzyme (ACE) inhibitors that lowered blood pressure in aorta-coarcted renal hypertensive rats. The most active derivatives are 1-[3(R)-(acetylthio) -3-substituted-benzoyl)-2(S)-methyl-propionyl]-L-prolines with an in vivo activity equivalent to SQ 14,225 (captopril). Structure-activity relationships are discussed. Changes in the configuration of the alpha-methyl group and the S-acetyl group affect the ACE activity. Coupling of 3-(substituted-benzoyl)-2-methylpropionic acids to L-proline via enol lactones is described.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Potential antiatherosclerotic agents. 2. (Aralkylamino)- and (alkylamino) benzoic acid analogues of cetaben.

The syntheses of a series of (aralkylamino)- and (alkylamino)benzoic acids, as well as the corresponding esters and sodium salts, are described. The compounds were evaluated in vivo in rats for serum sterol and triglyceride lowering activity and in vitro for activity in inhibiting the principle cholesterol-esterifying enzyme of the arterial wall, fatty acyl-CoA:cholesterol acyltransferase (ACAT). Based on a combination of these two activities, cataben sodium (150) was selected for development as a hypolipidemic and potential antiatherosclerotic agent.

4-Aminobenzoic Acid↗
PubMed1983

Potential antiatherosclerotic agents. 3. Substituted benzoic and non benzoic acid analogues of cetaben.

The synthesis of a series of analogues in which the carboxylic acid group of cetaben is replaced by carboxylate ester, carboxamide, or a variety of other substituent groups is described. Also reported are the syntheses of analogues in which the phenyl ring of cetaben is either modified by the presence of additional substituents or replaced entirely by another moiety. Structure-activity relationships of these compounds both as hypolipidemic agents and as inhibitors of the enzyme fatty acyl-CoA:cholesterol acyltransferase (ACAT) are discussed. Analogue syntheses designed to produce compounds that would be better absorbed orally than cetaben failed to yield any congeners of enhanced biological activity. In contrast, analogue syntheses directed toward non carboxylic acids of similar acidity to cetaben produced a very active class of sulfonamides.

4-Aminobenzoic Acid↗
PubMed1981

Synthesis and anxiolytic activity of 6-(substituted-phenyl)-1,2,4-triazolo[4,3-b]pyridazines.

The synthesis of a series of 6-(substituted-phenyl)-1,2,4-triazolo[4,3-b]pyridazines (VIII) is reported. Some of these derivatives show activity in tests predictive of anxiolytic activity [(a) protection against pentylenetetrazole-induced convulsions; (b) thirsty rat conflict procedure]. They also represent a new class of compound which inhibits [3H]diazepam binding. Structure--activity correlations, as well as the ability of structures VIII to inhibit [3H]diazepam binding (in vitro), are discussed.

Animals↗
PubMed1979

(Aryloxy)[p-(aryloxy)phenyl]- and (aryloxy)[p-(arylthio)phenyl]acetic acids and esters as hypolipidemic agents.

A series of (aryloxy)[p-(aryloxy)phenyl]- and (aryloxy)[p-(arylthio)phenyl]acetic acids and esters of general structure 8 were prepared and tested for lipid-lowering activity in normal rats. At a dose of 0.1% of the diet (ca. 100 mg/kg), approximately half of the compounds reduced serum sterols in the range of 20--30% and lowered serum triglycerides by 40--60%. Over 35 analogues lowered serum sterols by 15--25% when fed at 0.03% of diet, and 15 of these maintained their activity at 0.01% of the diet (10 mg/kg). Synthetic methodology and structure-activity relationships are discussed.

Animals↗