356057-34-6
356057-34-6 structure
- Name: Darapladib
- Chemical Name: N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide
- CAS Number: 356057-34-6
- Molecular Formula: C36H38F4N4O2S
- Molecular Weight: 666.771
- Catalog: Biochemical Inhibitor Metabolism Phospholipase (eg PLA) inhibitor
- Create Date: 2018-06-01 08:00:00
- Modify Date: 2024-01-06 11:11:54
-
Darapladib is a potent inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) with IC50 of 0.25 nM.
| Name | N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide |
|---|---|
| Synonyms |
N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylthio]-4-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide
Darapladib (USAN) Darapladib 1H-Cyclopenta[d]pyrimidine-1-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]- N-[2-(Diethylamino)ethyl]-2-{2-[(4-fluorobenzyl)sulfanyl]-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl}-N-{[4'-(trifluoromethyl)-4-biphenylyl]methyl}acetamide UNII-UI1U1MYH09 |
| Description | Darapladib is a potent inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) with IC50 of 0.25 nM. |
|---|---|
| Related Catalog | |
| Target |
IC50: 0.25 nM (Lp-PLA2)[1] |
| In Vitro | Mechanistic studies using steady state and transient kinetics indicate Darapladib (SB-480848) to be a freely reversible, non-covalently bound, inhibitor of rhLp-PLA2 with a Ki of 110 pM and an off-rate of 27 min. Potent inhibition of the enzyme in whole human plasma is confirmed (IC50=5±2 nM). Furthermore, the presence of Darapladib during the copper catalysed oxidation of human LDL prevents the production of lyso-PtdCho (IC50=4±3 nM) and subsequent monocyte chemotaxis (IC50=4±1 nM)[1]. |
| In Vivo | Additional in vivo studies with Darapladib indicated an oral bioavailability of 11±2% in the fed rat. The oral bioavailability of Darapladib is 28±4% in the dog. Furthermore excellent inhibition of Lp-PLA2 within the atherosclerotic plaque is achieved for Darapladib, with 95±1% inhibition observed 2 h after an oral dose of 30 mg/kg to the WHHL rabbit[1]. Darapladib, a specific inhibitor of lipoprotein-associated phospholipase A2 (lp-PLA2), on inflammation and atherosclerotic formation in the low density lipoprotein receptor (LDLR)-deficient mice. the activity of serum lp-PLA2 is inhibited by more than 60% in LDLR-deficient mice after oral administration of 50 mg/kg once daily of Darapladib for 6 weeks. Darapladib significantly inhibits serum lp-PLA2 activity in LDLR-deficient mice[2]. |
| Animal Admin | Mice[2] Male homozygous LDLR-deficient mice (C57/Bl6 genetic background) are fed a high-fat diet consisting of 18% hydrogenated cocoa butter, 0.15% cholesterol, 7% casein, 7% sucrose, and 3% maltodextrin for 17 weeks, beginning at 6 weeks of age. Forty mice are divided into two groups (n=20 per group) randomly. One group receive Darapladib by gavage (50 mg/kg per day) once daily, while the other group receive the vehicle (saline). During the 6 weeks of treatment, all mice are housed in a room with a 12-h light/dark cycle and are allowed free access to a high-fat diet and water. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 741.0±70.0 °C at 760 mmHg |
| Molecular Formula | C36H38F4N4O2S |
| Molecular Weight | 666.771 |
| Flash Point | 401.9±35.7 °C |
| Exact Mass | 666.265137 |
| PSA | 83.74000 |
| LogP | 8.27 |
| Vapour Pressure | 0.0±2.4 mmHg at 25°C |
| Index of Refraction | 1.594 |
| Storage condition | -20°C |