356057-34-6

Basic information

• 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;N-[2-(Diethylamino)ethyl]-N-[4'-(trifluoromethyl)-1,1'-biphenyl-4-ylmethyl]-2-[2-(4-fluorobenz
• CAS NO: 356057-34-6
• Molecular Formula: C36H38F4N4O2S
• Molecular Weight: 666.79
• Product Categories: Inhibitors
• Mol File: 356057-34-6.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 741.002 °C at 760 mmHg
• Flash Point: 401.944 °C
• Appearance: /
• 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
• PKA: 9.03±0.10(Predicted)
• CAS DataBase Reference: DARAPLADIB(CAS DataBase Reference)
• NIST Chemistry Reference: DARAPLADIB(356057-34-6)
• EPA Substance Registry System: DARAPLADIB(356057-34-6)

Safety Data

• Hazardous Substances Data: 356057-34-6(Hazardous Substances Data)

Usage

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

Different sources of media describe the Uses of 356057-34-6 differently. You can refer to the following data:
1. Treatment of atherosclerosis.
2. 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].

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.

Upstream product

• 90035-34-0 4-(4-trifluoromethylphenyl)benzaldehyde 
• 1122-91-4 4-bromo-benzaldehyde 
• 128796-39-4 4-trifluoromethylphenylboronic acid 
• 1349902-20-0 2-(4-oxo-2-thioxo-2,3,4,5,6,7-hexahydro-1H-cyclopenta-[d]-pyrimidin-1-yl) acetic acid 
• 1349902-19-7 sodium ({2-[(methyloxy)carbonyl]-1-cyclopenten-1-yl}amino)acetate 
• 356058-42-9 {2-[(4-fluorobenzyl)sulfanyl]-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl}acetic acid 
• 1349902-21-1 C₁₉H₁₇FN₄O₂S 
• 304694-40-4 N,N-diethyl-N'-(4'-trifluoromethylbiphenyl-4-ylmethyl)ethane-1,2-diamine 
• 10472-24-9 methyl 2-oxocyclopentane-1-carboxylate 
• 100-36-7 N,N-diethylethylenediamine 
• 451487-18-6 2-[(4-fluorobenzyl)sulfanyl]-1,5,6,7-tetrahydro-4H-cyclopenta[d]pyrimidin-4-one 
• 35563-27-0 2-mercapto-1,5,6,7-tetrahydro-cyclopentapyrimidin-4-one 
• 611-10-9 2-ethoxycarbonyl-1-cyclopentanone 

Relevant articles and documents

RADIOLABELED DARAPLADIB AND ANALOGS THEREOF AND THEIR USE AS IMAGING COMPOUNDS

The present inventors have developed new radiolabeled Darapladib and analogs thereof which can be used for the specific detection of vulnerable atherosclerotic plaques by targeting lipoprotein-associated phospholipase A2 (Lp-PLA2) which is a biomarker of

Compounds

Pyrimidone compounds of formula (I): are inhibitors of the enzyme Lp-PLA2 and are of use in treating atherosclerosis.

Selective inhibitors and tailored activity probes for lipoprotein- associated phospholipase A2

Lipoprotein-associated phospholipase A2 (Lp-PLA2 or PLA2G7) binds to low-density lipoprotein (LDL) particles, where it is thought to hydrolyze oxidatively truncated phospholipids. Lp-PLA2 has also been implicate