Disease relevance of phthalazine

• Evaluation of apoptosis-induction by newly synthesized phthalazine derivatives in breast cancer cell lines [1].

High impact information on phthalazine

• PTK787/ZK 222584 (1-[4-chloroanilino]-4-[4-pyridylmethyl] phthalazine succinate) is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, active in the submicromolar range [2].
• These results show that novel PDE5 inhibitors possessing a potent vasorelaxant effect may exist among phthalazine derivatives [3].
• The interaction of a series of 1-substituted phthalazine derivatives with partially purified aldehyde oxidase from rabbit, guinea-pig and baboon liver, and with bovine milk xanthine oxidase, has been investigated [4].
• Phthalazine-based dinucleating ligands afford dinuclear centers often encountered in metalloenzyme active sites [5].
• Incubation of hydralazine with activated neutrophils or monocytes led to the production of phthalazinone, phthalazine and 3 unidentified metabolites [6].

Biological context of phthalazine

• The structure of the unknown metabolite based on mass spectral analyses is proposed to be a dimerization product consisting of P and 1-aminophthalazine [7].
• Laboratory assessment of environmental impact of phthalazine [8].

Anatomical context of phthalazine

• Formation of the metabolites, with the exception of phthalazine, required activation of the leukocytes [6].
• The results of incubations with [14C]HP indicated that P and the unknown metabolite were quantitatively the major metabolites and were produced in similar quantities by rat liver microsomes [7].
• Liver cytosol exhibited extremely high benzaldehyde and phthalazine oxidase activities based on aldehyde oxidase, compared with those of rabbits, rats, mice and guinea pigs [9].

Associations of phthalazine with other chemical compounds

• Hydralazine was metabolized in vitro to phthalazine and phthalazine-1-one by microsomal enzymes requiring NADPH [10].
• Quantitative study of the structural requirements of phthalazine/quinazoline derivatives for interaction with human liver aldehyde oxidase [11].
• Correlations were observed between M2 formation and the metabolism of the aldehyde oxidase substrates phenanthridine (r(2) = 0.774) and phthalazine (r(2) = 0.460) [12].
• Enzymatic oxidation of phthalazine with guinea pig liver aldehyde oxidase and liver slices: inhibition by isovanillin [13].

Gene context of phthalazine

• Arylphthalazines: identification of a new phthalazine chemotype as inhibitors of VEGFR kinase [14].
• Aldehyde oxidase activity (assessed by the 1-hydroxylation of phthalazine) declined to approximately 20% of the initial value by 48 hr in culture [15].
• This communication describes the synthesis and in vitro evaluation of a novel and potent series of phthalazine phosphodiesterase type (IV) (PDE4) inhibitors [16].
• Phthalazine PDE4 inhibitors. Part 3: the synthesis and in vitro evaluation of derivatives with a hydrogen bond acceptor [16].
• For the phthalazine derivative the yield pressure increased as particle size decreased; however the SRS index reduced from 41% to zero, indicating that the deformation mechanism was changing from plastic flow to brittle behaviour [17].

References