The Bioavailability of the Novel Nonnucleoside Reverse Transcriptase Inhibitor GW420867X Is Unaffected by Food in Healthy Male Volunteers

Abstract

The effect of food on the bioavailability of GW420867X, a novel nonnucleoside reverse transcriptase inhibitor, was investigated in 15 young, healthy, male volunteers. A single oral dose of GW420867X 100 mg was administered in the fasted state, after a high-fat meal, and after a meal of normal fat composition. Tolerability and pharmacokinetic sampling were assessed at baseline and up to 600 hours. The median concentration-time plots for each treatment group were essentially superimposable. Neither the rate nor the extent of absorption of GW420867X was significantly affected by food. The median time to peak plasma concentration was 3 to 4 hours, irrespective of treatment. Pairwise comparisons using the fasted treatment as the comparator showed no impact of food on GW420867X pharmacokinetics. GW420867X was well tolerated. There were no serious or treatment-limiting adverse events; all episodes reported were rated as mild to moderate. The bioavailability of GW420867X was unaffected by food. GW420867X may be administered independently of food and fat intake.

Photocatalytic Giese Addition of 1,4-Dihydroquinoxalin-2-ones to Electron-Poor Alkenes Using Visible Light

“…Moreover, 1,4-dihydroquinoxalinones constitute a prevalent skeleton frequently found in many biologically active compounds (Scheme C). Many examples are used as pharmaceuticals, including antiviral compounds used for the treatment of HIV, anticancer compounds, cholesteryl ester transfer protein inhibitors, and anti-inflammatory compounds . Therefore, continuing with our interest in the oxidative functionalization of cyclic amines, we described the radical addition of 1,4-dihydroquinoxalin-2-ones to a wide range of electron-deficient olefins using a catalytic system formed by Ru­(bpy) 3 Cl 2 and (PhO) 2 PO 2 H under blue LED irradiation.…”

A Combination of Visible-Light Organophotoredox Catalysis and Asymmetric Organocatalysis for the Enantioselective Mannich Reaction of Dihydroquinoxalinones with Ketones

“…In particular, dihydroquinoxalinones constitute a prevailing scaffold frequently found in many biologically active natural and synthetic products (Figure ). Many examples are used as pharmaceuticals, including antiviral compounds, used for the treatment of HIV, anticancer compounds, cholesteryl ester transfer protein inhibitors, antiinflammatory compounds, antitumor agents, and also as agrochemicals . However, enantioselective approaches to the synthesis of chiral dihydroquinoxalin-2-ones are scarce and limited to catalytic asymmetric hydrogenations of quinoxalinones. , In view of the few examples of the catalytic asymmetric methodologies for the synthesis of such compounds, we envisioned that the corresponding quinoxalin-2-one generated under mild conditions from 3,4-dihydroquinoxalin-2-one by a photocatalyzed oxidation might react with carbonyl compounds using asymmetric enamine catalysis giving a Mannich product.…”

The First General, Efficient and Highly Enantioselective Reduction of Quinoxalines and Quinoxalinones

“…[7] Furthermore, due to the similarity in their structure, tetrahydroquinoxalines are used as models for tetrahydrofolic acids (coenzyme F) and their derivatives, for example, leucovorine.…”