Auranofin C화학적 특성, 용도, 생산
개요
Auranofin is the first orally effective gold compound to be marketed for the
treatment of severe rheumatoid arthritis. It is better tolerated and more
convenient than gold sodium thiomalate, which is administered intramuscularly.
화학적 성질
White to Off-White Solid
용도
Auranofin is a new oral gold-based antiarthritis drug. Auranofin inhibits various leukocyte activation pathways at multiple sites. Auranofin inhibits the release of inflammatory mediators from human m
acrophages, basophils, and pulmonary mast cells. Auranofin is an efficient inducer of mitochondrial membrane permeability transition pore in the presence of calcium ions related to its inhibition of m
itochondrial thioredoxin reductase.
정의
ChEBI: An S-glycosyl compound consisting of 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranose with the sufur atom coordinated to (triethylphosphoranylidene)gold. It is administered orally fo
the treatment of active progressive rheumatoid arthritis.
Pharmaceutical Applications
Auranofin ([tetra-O-acetyl-β-D- (glucopyranosyl)thio]-triethylphosphine)gold(I) is a second-generation gold-based drug, licensed as an orally available gold drug for the treatment of RA. It features a linear S Au P geometry, as shown by X-ray analysis. It is more lipophilic than the first-generation drugs, which makes oral administration possible. Treatment with Auranofin requires less visits to the clinic, but it is believed to be less successful in the treatment of RA compared to gold drugs being administered intramuscularly.
Clinical Use
Auranofin is indicated in adults with active rheumatoid arthritis who have not responded sufficiently to one or more
NSAIDs.
Safety Profile
Poison by ingestion,intraperitoneal, and intravenous routes. Human systemiceffects by ingestion: ulceration or bleeding from stomach.An experimental teratogen. Other experimentalreproductive effects. Human mutation data reported.When heated to decomp
Synthesis
Synthesis: ethanolic thiodiglycol is treated
first with aqueous gold(I) acid chloride trihydrate, then with ethanolic triethylphosphine to
give triethylphosphine gold(I) chloride, which is
added to an aqueous solution of S-(2,3,4,6-tetra-O-acetylglucopyranosyl)pseudothiourea hydrobromide and potassium carbonate to give the desired auranofin.
신진 대사
On a mg gold/kg basis, it is reported to be as effective in the rat adjuvant arthritis assay as the parenterally
effective drugs. Daily oral doses produce a rapid increase in kidney and blood gold levels for the first 3 days of
treatment, with a more gradual increase on subsequent administration. Plasma gold levels are lower than those
attained with parenteral gold compounds. The major route of excretion is via the urine. Auranofin may produce fewer
adverse reactions than parenteral gold compounds, but its therapeutic efficacy also may be less.
Auranofin 준비 용품 및 원자재
원자재
준비 용품
