ABSTRACT
A series of 2-alkylisoflavone derivatives 1 was prepared with the intent to study the importance of the phenyl group (at the 3-position) of the isoflavone in imparting antihypertensive activity and the substitution effects at the 2-position of isoflavone. With the exception of the 2-isopropyl analog, the antihypertensive activity of these compounds appears to have a slow onset and long duration. None of the analogs appears better than the corresponding flavone (3) and 3-phenylflavone (2) analogs. An unsuccessful attempt to correlate the relationship between antihypertensive activity and the calculated torsional angle of C2-C3-C1'-C2' is discussed. Antiinflammatory activities of these compounds along with 7-(oxypropylamine)flavones were also evaluated and found to be not very potent. The antiinflammatory activity appears to be sensitive to steric effects of the alkyl group on the nitrogen and of substituents at the 2-position of the isoflavones, while the hydroxyl group of the propanolamine side chain is not essential.
Subject(s)
Antihypertensive Agents/chemical synthesis , Flavonoids/chemical synthesis , Animals , Anti-Inflammatory Agents , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antihypertensive Agents/chemistry , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Flavonoids/chemistry , Flavonoids/pharmacology , Male , Molecular Conformation , Rats , Rats, Inbred SHR , Rats, Sprague-Dawley , Structure-Activity RelationshipABSTRACT
A series of substituted 11-oxo-11H-pyrido[2,1-b]quinazoline-8-carboxylic acids were prepared and evaluated as antiallergy agents. Several analogues were orally active. 2-Methyl-11-oxo-11H-pyrido[2,1-b]quinoazoline-8-carboxylic acid (6) was superior to cromolyn sodium and doxantrazole orally and intravenously in the rat PCA test and a rat allergic bronchospasm model.
Subject(s)
Hypersensitivity/drug therapy , Quinazolines/chemical synthesis , Animals , Bronchial Spasm/drug therapy , Bronchial Spasm/immunology , Bronchial Spasm/physiopathology , Histamine Release/drug effects , In Vitro Techniques , Mast Cells/drug effects , Mast Cells/immunology , Passive Cutaneous Anaphylaxis/drug effects , Pulmonary Ventilation/drug effects , Quinazolines/pharmacology , Rats , Structure-Activity RelationshipABSTRACT
Pregnancies in hamsters may be terminated by 10 mug PGF2alpha administered b.i.d. on days 4, k and 6 of gestation. Small (250 mug and above) daily injections of progesterone on the same days will reverse this PG effect; in contradistinction, 10 mg of progesterone per day failed to maintain normal pregnancies in hamsters spayed on day 5. Daily administration of 3 mg of progesterone and 1 mug of estrone essentially normalized the gestation; administration of PGF2alpha at 10 mg on days 5, 6 and 7 of pregnancy in steroid-maintained rats, resulted in pregnancy termination in all animals, while 1 mg was partly effective. These data demonstrate an extra-ovarian site of action of prostaglandin F2alpha on pregnancy in hamsters.
