Inhibitors of blood platelet cAMP phosphodiesterase: a QSAR analysis.
A quantitative structure-activity relationship (QSAR) analysis of two related series of the derivatives of 7-substituted imidazo [4,5-b]-quinolin-2-one active as inhibitors of human blood platelet cAMP phosphodiesterase (PDE) is presented with a view to reflecting upon the parametric requirements of the side chain as well as of the N-1 and N-3 substitutions on the heterocycle. For the first series (Figure 1) consisting of 114 congeners and having a more flexible functionalized side chain at the 7-position and only binary variations (Me or H) at N-1 and N-3, it has been shown that bulk (Vw), of the functionalized side chain tends to potentiate the inhibitory activity of a derivative while positions N-1 and N-3 should better remain unsubstituted, as reflected through the dummy variables. A similar analysis of the compounds of the second series (Figure 2), where a less flexible side chain is linked through a basic nitrogen, has provided a parabolic dependence of inhibition activity on Vw. From this relationship, a limiting size of the side chain, seems to be necessary for triggering a minimal response.
Tiwari
S
S
Department of Chemistry, S.K. Government College, Sikar, India.
Sharma
R C
RC
Ojha
T N
TN
Singh
P
P
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
D007527:Isoenzymes; D015105:3',5'-Cyclic-AMP Phosphodiesterases