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| Product Name: | DARAPLADIB | | Synonyms: | 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;SB 435445;SB 480848;Darapladib API;Darapladib(SB-480848);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;DARAPLADIB;SB-480848;SB480848 | | CAS: | 356057-34-6 | | MF: | C36H38F4N4O2S | | MW: | 666.77 | | EINECS: | | | Product Categories: | Inhibitors | | Mol File: | 356057-34-6.mol |  |
| | DARAPLADIB Chemical Properties |
| 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) | | color | White to off-white |
| | DARAPLADIB Usage And Synthesis |
| 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.
| | Uses | Treatment of atherosclerosis. | | Uses | Darapladib (SB-480848) is a reversible lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor. | | 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. | | in vitro | darapladib potently inhibited lp-pla2 with an ic50 of 270 pm. a lack of selectivity against other secretory pla2s postulated to play a role in atherogenesis had been demonstrated. the percentage inhibition achieved when 1 μm darapladib was evaluated against human secretory pla2s iia, v and x, was 0, 0 and 8.7%, respectively [1]. | | in vivo | inhibition of lp-pla2 by darapladib led to attenuation of inflammation in vivo and decreased plaque formation in apoe-deficient mice, suggesting an anti-atherogenic role during the progression of atherosclerosis [2]. | | 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. |
| | DARAPLADIB Preparation Products And Raw materials |
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