1373215-15-6
基本信息
N-[(3R,4S)-3,4-二氢-3-[[(甲基氨基)羰基]氧基]-6-[4-(3-氧杂环丁基)-1-哌嗪基]-2H-1-苯并吡喃-4-基]-4-氟-苯甲酰胺
Z-FL-COCHO
CATHEPSIN S INHIBITOR
CATHEPSIN S INHIBITOR
LY-3000328
LY3000328
((3R,4S)-4-((4-FLUOROBENZOYL)AMINO)-6-(4-(OXETAN-3-YL)PIPERAZIN-1-YL)CHROMAN-3-YL)N-METHYLCARBAMATE
N-[(3R,4S)-3,4-Dihydro-3-[[(methylamino)carbonyl]oxy]-6-[4-(3-oxetanyl)-1-piperazinyl]-2H-1-benzopyran-4-yl]-4-fluorobenzamide
Benzamide, N-[(3R,4S)-3,4-dihydro-3-[[(methylamino)carbonyl]oxy]-6-[4-(3-oxetanyl)-1-piperazinyl]-2H-1-benzopyran-4-yl]-4-fluoro-
物理化学性质
| 沸点 | 701.6±60.0 °C(Predicted) |
| 密度 | 1.38±0.1 g/cm3(Predicted) |
| 储存条件 | -20°C储存 |
| 溶解度 | ≥24.25 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| 酸度系数(pKa) | 12.50±0.46(Predicted) |
| 形态 | 粉末 |
| 颜色 | White to off-white |
安全数据
| 危险性符号(GHS) |  GHS07 |
| 警示词 | 警告 |
| 危险性描述 | H302-H315-H319-H335 |
| 防范说明 | P261-P305+P351+P338 |
| 海关编码 | 2934999090 |
图谱信息
((3R,4S)-4-((4-FLUOROBENZOYL)AMINO)-6-(4-(OXETAN-3-YL)PIPERAZIN-1-YL)CHROMAN-3-YL)N-METHYLCARBAMATE(1373215-15-6)质谱(MS)((3R,4S)-4-((4-FLUOROBENZOYL)AMINO)-6-(4-(OXETAN-3-YL)PIPERAZIN-1-YL)CHROMAN-3-YL)N-METHYLCARBAMATE(1373215-15-6)核磁图(1HNMR)常见问题列表
IC50: 7.7±5.85 nM (hCat S), 1.67±1.17 (mCat S)
LY3000328 maintains excellent in vitro potency and selectivity. LY3000328 shows low in vitro CYP450 inhibition (<15% at 10 μM for CYP3A4, CYP2D6, and CYP2C9); low in vitro metabolism in mouse, rat, dog, and human liver microsomes (<20% after 30 min incubation at 4 μM); and good permeability (MDCK A-B>4%). At a 100 μM concentration of LY3000328 there is only 6% displacement of [ 3 H]-astemizole in an assay with HEK293 membrane preparation, indicating low potential of hERG blockade. LY3000328 is a potent and specific inhibitor of cathepsin S (CatS). Inhibition of CatS activity in plasma would be 50% of maximal when LY3000328 plasma concentration is approximately 60 ng/mL.
The efficacies of LY3000328 is studied in a mouse model of abdominal aortic aneurysm (AAA). In this model, inflammation is induced using CaCl 2 applied to the ablumenal surface. It is shown that features of the disease state in this model resemble those of human AAA. LY3000328 exhibits a dose-responsive aortic diameter reduction at 1, 3, 10, and 30 mg/kg. At the lowest dose of 1 mg/kg of LY3000328, the aortic diameter is reduced by 58%, then 83% at 3 mg/kg, and 87% at 10 mg/kg. The exposure (AUC) for both compounds increased in a dose-dependent manner, suggesting that the drug disposition properties of LY3000328 are favorable.