Disease relevance of NSC342435

• Inhibition of HIV-1 reverse transcriptase by a quinazolinone and comparison with inhibition by pyridinones. Differences in the rates of inhibitor binding and in synergistic inhibition with nucleoside analogs [1].

High impact information on NSC342435

• The quinazolinone and pyridol-pyrimidine classes of p38 MAP kinase inhibitors have a previously unseen degree of specificity for p38 over other MAP kinases [2].
• We have previously demonstrated that halofuginone, a low molecular weight quinazolinone alkaloid, is a potent inhibitor of collagen alpha1(I) and matrix metalloproteinase 2 (MMP-2) gene expression [3].
• To facilitate its pharmacological characterization, we screened a compound library and identified a substituted quinazolinone (Quin-C1, 4-butoxy-N-[2-(4-methoxy-phenyl)-4-oxo-1,4-dihydro-2H-quinazolin-3-yl]-benzamide) as a ligand for FPRL1 [4].
• Halofuginone, a low-molecular-weight quinazolinone alkaloid, is a potent inhibitor of collagen type alpha1 (I) gene expression and ECM deposition [5].
• A novel class of quinazolinone derivatives as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors has been discovered [6].

Chemical compound and disease context of NSC342435

• Efavirenz and a series of related quinazolinone nonnucleoside inhibitors of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) were evaluated in a series of two-drug combinations with several nucleoside RT inhibitors (NRTIs), nonnucleoside RT inhibitors (NNRTIs), and protease inhibitors (PIs) [7].

Biological context of NSC342435

• Extensive structure-activity relationship studies suggest that the entire quinazolinone structure was required, but activity was further enhanced by halide or small hydrophobic substituents at position 6 [8].
• Resistance-modifying agents. 5. Synthesis and biological properties of quinazolinone inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) [9].
• Effects of MCI-176, a new quinazolinone calcium antagonist, on myocardial energy and carbohydrate metabolism in ischemic dog hearts [10].
• CONCLUSIONS: Based on these molecular descriptors, the quinazolinone derivative MCI-176 is predicted to be a potential ligand of the diltiazem binding site [11].
• Kinetic studies of 2-(2'-Haloethyl) and 2-ethenyl substituted quinazolinone alkylating agents. Acid-catalyzed dehydrohalogenation and alkylation involving a quinazolinone prototropic tautomer [12].

Anatomical context of NSC342435

• We compared the coronary vasodilator and cardiac effects of MCI-176, a novel quinazolinone calcium antagonist, in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs [13].

Associations of NSC342435 with other chemical compounds

• The effect on enzyme inhibition of varying the N10 substituent of 2h was similar to that observed in the quinazolinone-containing antifolates, indicating that the quinoline compounds may be interacting with the enzyme in a similar way to the quinazolinones [14].
• Our aim was to identify a PARP inhibitor for clinical trial from a panel of 42 potent PARP inhibitors (K(i), 1.4-15.1 nmol/L) based on the quinazolinone, benzimidazole, tricyclic benzimidazole, tricyclic indole, and tricyclic indole-1-one core structures [15].
• Results obtained from this study suggest that the antihyperlipidemic effect of quinazolinone compounds was brought about by inhibition of dietary cholesterol absorption and / or intestinal ACAT activity [16].

Gene context of NSC342435

• The syntheses and SAR studies of various quinazolinone compounds are described for the dual inhibition of Pgp and MRP1 in multidrug resistance [17].
• Quinazolinone derivatives: synthesis and binding evaluation on cholecystokinin receptors [18].
• Synthesis and X-ray crystallographic analysis of quinazolinone cholecystokinin/gastrin receptor ligands [19].
• Since asperlicin, a selective CCK-A receptor antagonist, may be regarded as a conformationally constrained 2-substituted-3-phenyl-4(3H)-quinazolinone, the progenitor of compound 3 (compound 2, 2-[2-(1H-indol-3-yl)ethyl]-3-phenyl-4(3H)- quinazolinone) might therefore represent a conformationally flexible pharmacophore of the natural product [19].
• A series of 2-aralkyl-4H-pyridothiadiazine 1,1-dioxides and 3-aralkylamino-2-aryl-2H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to quinazolinone CCK receptor antagonists were synthesized and evaluated as CCK-A and CCK-B receptor ligands [20].

Analytical, diagnostic and therapeutic context of NSC342435

• HPLC assay in plasma and preliminary pharmacokinetic study of a quinazolinone derivative with spasmolytic effect [21].
• Recently, small moleculer inhibitors of one kinesin, kinesin spindle protein (KSP/Eg5/kinesin5), have been shown to be efficacious in pre-clinical studies, with one quinazolinone-based inhibitor advancing to Phase II clinical trials as a potential anticancer chemotherapeutic agent [22].

References