| Identification | Back Directory | [Name]
DARAPLADIB | [CAS]
356057-34-6 | [Synonyms]
SB 435445
SB 480848
Darapladib API
Darapladib(SB-480848)
N-[2-(Diethylamino)ethyl]-N-[4'-(trifluoromethyl)-1,1'-biphenyl-4-ylmethyl]-2-[2-(4-fluorobenz
N-[2-(Diethylamino)ethyl]-N-[4'-(trifluoromethyl)-1,1'-biphenyl-4-ylmethyl]-2-[2-(4-fluorobenzylthio)-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl]acetamide
N-[2-(diethylamino)ethyl]-2-[[(4-fluorophenyl)methyl]thio]-4,5,6,7-tetrahydro-4-oxo-N-[[4'-(trifluoromethyl)[1,1'-biphenyl]-4-yl]methyl]-1H-Cyclopentapyrimidine-1-acetamide
N-(2-(Diethylamino)ethyl)-2-(2-((4-fluorobenzyl)thio)-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl)-N-((4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methyl)acetamide | [Molecular Formula]
C36H38F4N4O2S | [MDL Number]
MFCD18251452 | [MOL File]
356057-34-6.mol | [Molecular Weight]
666.79 |
| Chemical Properties | Back Directory | [Boiling point ]
741.0±70.0 °C(Predicted) | [density ]
1.25 | [storage temp. ]
Inert atmosphere,Store in freezer, under -20°C | [solubility ]
≥32.95 mg/mL in DMSO; insoluble in H2O; ≥891 mg/mL in EtOH | [form ]
solid | [pka]
9.03±0.10(Predicted) |
| Questions And Answer | Back Directory | [Description]
Darapladib (SB-480848) is a reversible lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor with IC50 of 0.25 nM. Phase 3. | [In vitro]
During the copper catalysed oxidation of human LDL, Darapladib prevents the production of lyso-PtdCho with IC50 of 4 nM and subsequent monocyte chemotaxis with IC50 of 4 nM. | [In vivo]
In the WHHL rabbits, Darapladib (30 mg/kg p.o.) exhibits excellent inhibition of Lp-PLA2 within the atherosclerotic plaque by 95%. Darapladib, as an inhibitor of Lp-PLA2, reduces development of advanced coronary atherosclerosis in diabetic and hypercholesterolemic (DMHC) pigs. In DMHC pigs, darapladib reduces the amount of IgG-immunopositive material that leaked into the brain and also the density of Aβ42-containing neurons.
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| Hazard Information | Back Directory | [Uses]
Darapladib (SB-480848) is a reversible lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. | [Uses]
Treatment of atherosclerosis. | [Biological Activity]
plaque rupture is responsible for the clinical events of ischemic death, myocardial infarction, acute coronary syndromes and ischemic strokes. lipoprotein-associated phospholipase a2 (lp-pla2) seems to play a major role in the development of such high-risk lesions, in both the coronary and carotid arteries. darapladib is a selective inhibitor of lp-pla2. | [target]
Lp-PLA2 | [storage]
Store at -20°C | [References]
[1] bui qt, wilensky rl. darapladib. expert opin investig drugs. 2010;19(1):161-8.
[2] wang wy, zhang j, wu wy, li j, ma yl, chen wh, yan h, wang k, xu ww, shen jh, wang yp. inhibition of lipoprotein-associated phospholipase a2 ameliorates inflammation and decreases atherosclerotic plaque formation in apoe-deficient mice. plos one. 2011;6(8):e23425.
[3] mohler er 3rd, ballantyne cm, davidson mh, hanefeld m, ruilope lm, johnson jl, zalewski a; darapladib investigators. the effect of darapladib on plasma lipoprotein-associated phospholipase a2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double-blind, placebo-controlled study. j am coll cardiol. 2008;51(17):1632-41. |
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