Nuclear hydroxylated metabolite of fluradoline (2‐fluoro‐11‐[(β‐methylamino)ethylthio]dibenz[b,f]oxepin hydrochloride). Identification and synthesis

Abstract

Fluradoline (2‐fluoro‐11‐[β‐(methylamino)ethylthio]dibenz[b,f]oxepin), a novel analgesic with an unique profile, was found to be extensively metabolized in man as well as in other species. One of the major metabolites of this drug appeared to be a nuclear hydroxylated derivative of the parent compound, and the site of enzymatic hydroxylation was established to be C(7) by using high‐field proton nuclear magnetic spectroscopy. This structural assignment was subsequently confirmed by the synthesis of an authentic sample of 2‐fluoro‐7‐hydroxy‐11‐[β‐(methylamino)ethylthio]dibenz[b,f]oxepin (2a).

Synthesis and Study of Dibenzo[b, f]oxepine Combined with Fluoroazobenzenes—New Photoswitches for Application in Biological Systems

“…Then 50 equivalents of thionyl chloride were added. The mixture was heated at 80 °C under a reflux condenser for For compounds (5), UV-VIS spectra were also recorded at two concentrations of 50 and 500 µM. The spectrum for the lowest concentration of (5d) is shown in Figure 4, and the band π→π* can be observed.…”

“…Dibenzo[b, f ]oxepine derivatives are an important scaffold in natural, medicinal chemistry, and these derivatives occur in several medicinally relevant plants [1][2][3]. The dibenzo [b, f ] oxepine system can be associated with various biological properties such as antidepressant and anti-estrogenic [4], analgesic [5], anti-inflammatory [6], antipsychotic [7], angiotensin II receptor antagonistic [8], antioxidant [9], antimycobacterial [10], antidiabetic [11], and antitumor activities [3,12], as well as anti-apoptosis [13] properties. The treatment of progressive neurodegenerative diseases [14] such as Parkinson's and Alzheimer's diseases [15] with synthetic dibenzo[b, f ]oxepine derivatives is of particular interest.…”

A New Benzo[6,7]oxepino[3,2-b] Pyridine Derivative Induces Apoptosis in Canine Mammary Cancer Cell Lines

“…Dibenzo[b,f ]oxepine (DO) (Figure 1A) is an important structure in natural and medicinal chemistry, and its derivatives are found in various medicinally relevant plants [20,21]. Several compounds with DO rings have been reported to exhibit potent biological activities, including analgesic properties [22], antioxidant properties [23], antimycobacterial activity [24], anti-inflammatory activity [25], antidepressant activity [26], anti-apoptotic properties [27], and anticancer activities [28,29]. Studies of the pharmacological properties of DO derivatives have received much attention based on their fascinating structural features and health-promoting functions.…”

Exciting progress in the transition metal‐catalyzed synthesis of oxepines, benzoxepines, dibenzoxepines, and other derivatives

“…These compounds were found to have potential uses in pharmaceuticals [4][5][6] and also in polymers. The number of biological properties of these compounds is containing anti-inflammatory, [7][8][9] antiproliferative, [10] antitumor [1] and anticancer, [10] antiplasmodial, [11] antihelminthic activity, [12] antibiotic activity, [13][14][15][16] antiestrogenic, [17] analgesic, [18] antipsychotic, [9,[19][20][21] angiotensin II receptor antagonistic, [22] antioxidant, [23] antimycobacterial, [24] and antiapoptosis. [25] Some of oxepine, benzoxepine, and dibenzoxepine derivatives have been synthesized by Tishchenko-like reaction, [26] Friedel-Crafts acylation reactions, [27] Suzuki coupling, [28] and Catellani reaction.…”