title: Inhibitors of blood platelet cAMP phosphodiesterase: a QSAR analysis.
abstract: 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.
authors.affiliation: Department of Chemistry, S.K. Government College, Sikar, India.
authors.forename: S
authors.initials: S
authors.lastname: Tiwari
authors.forename: R C
authors.initials: RC
authors.lastname: Sharma
authors.forename: T N
authors.initials: TN
authors.lastname: Ojha
authors.forename: P
authors.initials: P
authors.lastname: Singh
mesh_terms: 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
chemical_list: D007527:Isoenzymes; D015105:3',5'-Cyclic-AMP Phosphodiesterases