GW501516 Chemische Eigenschaften,Einsatz,Produktion Methoden
Biologische Aktivit?t
GW 501516 is shown to be the most potent and selective PPARα agonists known with an EC50
of 1.1 nM against PPARα and 1000-fold selectivity over the other human
subtypes, PPARα and-γ. GW 501516 exerts anti-inflammatory effects in
mouse cultured proximal tubular (mProx) cells. GW 501516 inhibits
palmitate- and TNFα-induced increases in MCP-1 mRNA expression in a
dose-dependent manner.
Synthese
Add Cs2CO3
(3.25 g, 10.0 mmol), followed by the chloromethylthiazole (2.60 g) to a
stirred solution of 4-mercapto-2-methylphenol (1.40 g) in CH3CN (80
mL). Stir the reaction mixture at room temperature for 4 hours. Add Cs2CO3
(4.89 g, 15.0 mmol), followed by methyl bromoacetate (1.23 mL, 13.0
mmol) to the mixture. Stir the reaction mixture at room temperature for
another 5 hours. Pour the mixture into water. Extract the mixture with
EtOAc (3 x 100 mL). Combine the organic layers. Wash the organic layers
with brine. Dry the organic layers (Na2SO4). Concentrate the organic layers. Purify the residue by column chromatography on silica gel with hexane/ ethyl acetate (5:1). 1H NMR (CDCl3)
δ7.97 (d, 2H, J= 8.4 Hz), 7.65 (d, 2H, J= 8.4 Hz), 7.21 (d, 1H, J= 2.4
Hz), 7.13 (dd, 1H, J= 8.4, 2.4 Hz), 6.58 (d, 1H, J= 8.4 Hz), 4.63 (s,
2H), 4.11 (s, 2H), 3.78 (s, 3H), 2.24 (s, 3H), 2.20 (s, 3H). 13C NMR (CDCl3)
δ169.2, 163.0, 156.3, 151.3, 136.8, 136.1, 132.1, 131.2 (q, J= 32 Hz),
130.6, 128.4, 126.3, 125.8 (q, J= 4 Hz), 125.3, 122.1, 111.4, 65.4,
52.2, 32.4, 16.1, 14.8. 19F NMR (CDCl3) δ115.5 (s).
Fig. The synthetic step 1 of GW-501516
GW501516 Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
