Synthesis and antiinflammatory activity of some 1-alkyl-4-phenylpyrido[2,3-d]pyrimidin-2(1H)-ones

Protein Binding and Erythrocyte Partitioning of the Antirheumatic Proquazone

“…7a and 76, upon rearrangement Eq. 8 is obtained: cp = 102 (2) (Eq. 8) and cp can be calculated directly from the erythrocyte-buffer and erythrocyte-plasma partition coefficients.…”

“…Keyphrases 0 Proquazone-erythrocyte partitioning and equilibrium dialysis methods evaluated for determination of plasma protein binding of drug 0 Protein binding-proquazone in human plasma, erythrocyte partitioning and equilibrium dialysis methods evaluated Anti-inflammatory agents-proquazone, erythrocyte partitioning and equilibrium dialysis methods evaluated for determination of proquazone binding to plasma proteins Proquazonel, a new anti-inflammatory compound (1,2), exhibits antiphlogistic activities in animals and humans comparable to those of classical, nonsteroidal anti-inflammatory compounds (1-4). Its primary therapeutic indications are thought to be in the treatment of rheumatoid arthritis, osteoarthritis, and gouty arthritis (5,6).…”

Pharmacokinetics of the Antirheumatic Proquazone in Healthy Humans

“…The hexafluoroisopropyl esters of the N-ethylmaleimide adducts of captopril and of the internal standard, the 4-ethoxyproline analogue of captopril, were separated by GC on a column packed with Captopril, 1 -[ (2s) -3-mercapto-2-methylpropionyl] -],-proline (I), the first orally active inhibitor of angiotensin-converting enzyme (peptidyl dipeptide hydrolase, kininase 11, E.C. 3.4.15.1) to be used clinically, is a potent antihypertensive agent used to treat both renovascular and essential hypertension (1,2). It is of particular value in treating hypertension resistant to conventional drugs (31, and shows great promise for use in congestive heart failure (234).…”

“…oral and intravenous administration, NONLIN, SAAM 0 Antirheumaticsproquazone and its m-hydroxy metabolites, oral and intravenous pharmacokinetics in humans, NONLIN, SAAM Proquazone (I), a nonsteroidal anti-inflammatory drug (1,2) which has been marketed in several countries in Europe since 1977l, exhibits activities in animal models and humans comparable with those of classical nonsteroidal anti-inflammatory drugs (1-4). Its primary therapeutic indications are in the treatment of rheumatoid arthritis, osteoarthritis, and gouty arthritis (5, 6).…”

“…Later blood samples were taken by venipuncture". Blood samples (10 mL) were taken through the catheter with syringes using a three-way stopcock within 10 s at 0, 1.5,2,2.5,3,5,7,10, 15,20,25,30,40,50,60,75, and 90 min, 2,2.5,3,3.5,4,4.5,5,5.5,6,6.5, 7.5,8,9, and 10 h after intravenous administration of the drug and at 0, 2.5,5,7.5,10,15,20,30,45,60,75, and 90 min, 2,3,4,5,6,7,8,10,15,18,24,36,42, and 48 h after oral administration. A total volume of approximately 1200 mL of blood was obtained from the volunteers in the four studies within a period of three months.…”