ChemInform Abstract: Synthesis and Structure‐Activity Relationships of a Novel Class of 5‐Lipoxygenase Inhibitors. 2‐(Phenylmethyl)‐4‐hydroxy‐3,5‐dialkylbenzofurans: The Development of L‐656,224.

Abstract

Coupling of the substituted 2‐acetylresorcinols (I) with the phenacyl bromide (II) followed by in situ cyclization gives the 2‐benzoylbenzofurans (III).

Pseudoperoxidase activity of 5-lipoxygenase stimulated by potent benzofuranol and N-hydroxyurea inhibitors of the lipoxygenase reaction

“…The results in Figs. [2][3][4][5] support the hypothesis that the benzofuranol H and the hydroxyurea V can act as reductants for lipoxygenases, with recycling of the hydroxyurea inhibitor in the presence of DTT.…”

“…The enzyme 5-lipoxygenase catalyses the dioxygenation of arachidonic acid at the C-5 position as a first step in the leukotriene-biosynthesis pathway [1]. Considering the potential therapeutic applications of leukotriene-biosynthesis inhibitors in the treatment of asthma and inflammatory diseases, extensive studies on structure-activity relationships of 5-lipoxygenase inhibitors have been published on flavonoids, catechols, aminopyrazolines, benzofuranols and hydroxamate derivatives [2][3][4][5][6]. Much of the information available on the mechanism of inhibition of lipoxygenases by these classes of compounds has come from studies using soybean 15-lipoxygenase as a model [7][8][9][10][11][12][13].…”

“…The oxidation of arachidonic acid by 5-lipoxygenases appears to proceed through mechanisms similar to those described for the soybean enzyme, although the mammalian enzyme is less stable, requires ATP and Ca2+ as cofactors [15,16] and is subject to strong inhibition by compounds which are very poor inhibitors of the other lipoxygenases [2][3][4][5][6]. Studies' on the mechanism of 5-lipoxygenase inhibition have been limited by lack of information on the native enzyme, such as its content of metal ions, mainly due to the high enzyme lability.…”

Syntheses of 2‐Benzylbenzofuran Derivatives and 2‐Aryl‐nitro­chroman Derivatives from Nitro­alkene Precursors

“…Further, 2‐benzyl‐3‐biphenylylbenzofuran derivatives (Figure 1, B ) exhibit potent protein tyrosine phosphatase inhibitor activity and also have antihyperglycemic activity,4 S24014 ( C ) is an agonist of the melatonin receptors MT 1 and MT 2 ;5 and 656224 ( D ) is an inhibitor of bronchoconstriction and antigen‐induced dyspnea. It also inhibits the production of leukotriene B4 in polymorphonuclear leukocytes, which are involved in inflammation 6…”

Σύνθεση Και Φαρμακοχημική Μελέτη Νέων Αβ-Ακόρεστων Καρβοξυλικών Οξέων Και Παραγώγων Τους Με Πιθανή Δράση Κατά Της Φλεγμονής. Εφαρμογή Της Μεθόδου QSAR

“…Βιολογική Δράση = Συνολική Μέση Δραστικότητα + Άθροισμα Συνεισφοράς Υποκαταστατών Η πολλαπλή γραμμική ανάλυση παλινδρόμισης -(Multiple Linear Regression Analysis), επιτρέπει τη συσχέτιση μιας εξαρτημένης μεταβλητής με περισσότερες ανεξάρτητες μεταβλητές. Τα απαραίτητα στατιστικά στοιχεία, που πρέπει να συνοδεύουν την εξίσωση παλινδρόμισης είναι [Leo, 1971]: n: ο αριθμός των δεδομένων -ενώσεων. DF: n-K, οι βαθμοί ελευθερίας όπου K ο αριθμός των μεταβλητών.…”