Role of Tumor Necrosis Factor α in Acute and Chronic Inflammatory Responses: Novel Therapeutic Approaches

Carbocyclic Nucleosides as Inhibitors of Human Tumor Necrosis Factor-α Production: Effects of the Stereoisomers of (3-Hydroxycyclopentyl)adenines

“…The filtrate was concentrated in vacuo, the yellow oil was dissolved in ether (100 mL), 1 g of activated carbon was added, and the mixture was stirred for 5 min and filtered. The filtrate was evaporated to give 33 g of a colorless oil which was distilled bulb-to-bulb (80-90°C at 0.1 mmHg) to yield 20.0 g (55%) of 7a: 1 (1R,3S)-1-Acetoxy-3-(methylsulfonoxy)cyclopentane (8a). A solution of (1R,3S)-1-acetoxy-3-hydroxycyclopentane (7a, 49.0 g, 340 mmol) and methanesulfonyl chloride (46.7g, 408 mmol) in methylene chloride (425 mL) was stirred and cooled to 0-5°C (ice bath).…”

“…The aqueous layers were combined and extracted with methylene chloride (150mL), and the combined organic layers were dried (sodium sulfate) and concentrated in vacuo to give 3b (7.78 g, 100%) as a yellow oil. This material was used immediately without further purification: 1 Sodium adenide was prepared by adding adenine (14.40 g, 105.9 mmol) to dry DMF (250 mL) and was added to the slurry NaH (60% in mineral oil, 4.24 g, 105.9 mmol), and the reaction mixture was stirred for 3 h at 55-60°C. The (1R,4R)-1-acetoxy-4-[(methylsulfonyl)oxy]cyclopent-2-ene (3b) (7.78 g, 35.3 mmol) was added, and the reaction mixture was stirred for 48 h at 55-60°C.…”

“…Infrared (IR) spectra were recorded on a Mattson Galaxy Series 5020 infrared spectrophotometer with samples prepared as indicated, and are reported in wave numbers (cm -1 ). 1 H NMR spectra were recorded on Varian Gemini 300, Unity 300, Unity 400, or Unity 500 spectrometers with chemical shifts (δ) reported in ppm relative to tetramethylsilane (0.00 ppm). 13 C NMR spectra were recorded on the Varian Gemini instrument (75 MHz) with chemical shifts (δ) reported in ppm relative to CDCl3 (77.0 ppm), unless stated otherwise.…”

PEGylated recombinant human soluble tumour necrosis factor receptor type I (r-Hu-sTNF-RI): novel high affinity TNF receptor designed for chronic inflammatory diseases

“…7 These effects include anti-tumour activity,3 6 mediation of endotoxic shock and cachexia in infectious disease,8 9 augmentation of superoxide anion (O 2 - ) and hydrogen peroxide (H 2 O 2 ) release by neutrophils and macrophages,10 inhibition of viral replication, and potentiation of non-viral pathogen destruction by macrophages in vitro and in vivo 2. These studies and numerous others point out that TNFα is a major physiological cytokine important in mediating normal homeostatic mammalian processes 5…”

“…TNFα, a polypeptide cytokine, was discovered on the basis of its induction of haemorrhagic necrosis in certain murine tumours in vivo, and, independently, as a bloodborne mediator of cachexia during parasitic disease 7. It is produced by activated macrophages, T cells, and other cells, and has many activities in the immune system and in other systems.…”