160911-19-3Relevant academic research and scientific papers
Synthesis and QSAR of substituted 3-hydroxyanthranilic acid derivatives as inhibitors of 3-hydroxyanthranilic acid dioxygenase (3-HAO)
Linderberg, Mats,Hellberg, Sven,Bjoerk, Susanna,Gotthammar, Birgitta,Hoegberg, Thomas,Persson, Kerstin,Schwarcz, Robert,Luthman, Johan,Johansson, Rolf
, p. 729 - 744 (2007/10/03)
Novel 4,5-, 4,6-disubstituted and 4,5,6-trisubstituted 3- hydroxyanthranilic acid derivatives were synthesized and their ability to reduce the production of the excitotoxin quinolinic acid (QUIN) by inhibition of brain 3-hydroxyanthranilic acid dioxygenase (3-HAO) was subsequently investigated. The potency of the compounds to inhibit 3-HAO was assayed in rat brain homogenate, while chemical stability of certain compounds was studied by HPLC. The data were used to generate quantitative structure- activity relationship (QSAR) models for potency of 3-HAO inhibition and compound stability. Compounds with longer half-lives were obtained when the difference between the HOMO and LUMO was increased, while electron withdrawing groups in the 4- and 5-positions increased the potency of 3-HAO inhibition. Selected compounds that showed high potency in vitro were also found to be efficacious inhibitors in vivo after cerebral administration in rats.
NEW COMPOUNDS
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, (2008/06/13)
The present invention relates to novel derivatives of 3-hydroxyanthranilic acid, 3-HANA, of the general formula I wherein R1 and R2 are the same or different and selected from H, alkyl, aryl and arylalkyl; X and Y are the same or different and selected fr
