Benzeneacetamide, N-(2,4-difluorophenyl)-4-[[2-[4-(ethylsulfonyl)phenyl]acetyl]amino]-2-fluoro-α,α-dimethyl- CAS#: 2068119-11-7

Benzeneacetamide, N-(2,4-difluorophenyl)-4-[[2-[4-(ethylsulfonyl)phenyl]acetyl]amino]-2-fluoro-α,α-dimethyl-

中文名称	Benzeneacetamide, N-(2,4-difluorophenyl)-4-[[2-[4-(ethylsulfonyl)phenyl]acetyl]amino]-2-fluoro-α,α-dimethyl-
中文同义词	化合物S18-000003
英文名称	Benzeneacetamide, N-(2,4-difluorophenyl)-4-[[2-[4-(ethylsulfonyl)phenyl]acetyl]amino]-2-fluoro-α,α-dimethyl-
英文同义词	Benzeneacetamide, N-(2,4-difluorophenyl)-4-[[2-[4-(ethylsulfonyl)phenyl]acetyl]amino]-2-fluoro-α,α-dimethyl-;orphan,aberrations,ROR,acid,S18-000003,psoriasis,Inhibitor,RAR-related orphan receptor,retinoic,receptor-related,S18 000003,S-18-000003,RORγt,thymic,inhibit,S18000003
CAS号	2068119-11-7
分子式	C26H25F3N2O4S
分子量	518.55
EINECS号
相关类别
Mol文件	2068119-11-7.mol
结构式

Benzeneacetamide, N-(2,4-difluorophenyl)-4-[[2-[4-(ethylsulfonyl)phenyl]acetyl]amino]-2-fluoro-α,α-dimethyl- 性质

沸点	746.1±60.0 °C(Predicted)
密度	1.358±0.06 g/cm3(Predicted)
储存条件	Store at -20°C
溶解度	DMSO：100 mg/mL（192.85 mM；需要超声波）
形态	固体
酸度系数(pKa)	11.82±0.70(Predicted)
颜色	白色至黄色

Benzeneacetamide, N-(2,4-difluorophenyl)-4-[[2-[4-(ethylsulfonyl)phenyl]acetyl]amino]-2-fluoro-α,α-dimethyl- 用途与合成方法

生物活性

S18-000003 是一种有效，选择性和具有口服活性的维甲酸相关孤儿受体 (RORγt) 的抑制剂，在竞争性结合试验中，对 hRORγt 的 IC50 值小于 30 nM。S18-000003 对于 RORγt 的选择性高于其他 ROR 家族成员 (IC50s>10μM)。S18-000003 可用于研究银屑病，并且具有较低的胸腺畸变风险。

靶点

RORγt

<30 nM (IC ₅₀ )

体外研究

S18-000003 inhibits human and mouse RORγt-dependent transactivation, with IC ₅₀ s of 0.029 and 0.34 μM respectively in cell-based GAL4 promoter reporter assays.
S18-000003 (0.003-0.3 μM; 7 d) dose-dependently inhibits Th17 cell differentiation from human naive CD4 ⁺ T cells, with an IC ₅₀ of 0.024 μM.
S18-000003 (0.1-3 μM; 4 d) inhibits the differentiation of mouse Th17 cells from splenic naive CD4 ⁺ T cells, with an IC ₅₀ of 0.20 μM.
S18-000003 (0.03-1 μM; 3 d) reduces the IL-17 production in human PBMCs in a dose-dependent manner, and does not inhibit either the production of other cytokines (IL-2, IL-4, IL-10 and IFN-g) or cell proliferation.
S18-000003 (0.1-3 μM; 3 d) reduces IL-17 and IL-22 production in PBMCs from psoriatic mice in a dose-dependent manner.

体内研究

S18-000003 (30-100 mg/kg; p.o.) inhibits IL-17 production in the skin of IL-23-treated mice in a dose-dependent manner.
S18-000003 (0.1-8%; 100mL; topically administration once daily for 14 days) ameliorates psoriasis-like lesions in TPA-induced K14.Stat3C transgenic mice, and has little impact on the thymus.
S18-000003 (0.5 mg/kg; i.v.) exhibits the half-life (3.2 h), AUC (1930 ng•h/mL), CL _tot (4.33 mL/min/kg) and Vd _ss in rats.
S18-000003 (1 mg/kg; p.o.) exhibits the oral bioavailability (54.5%), C _max (185 ng/mL), AUC (2110 ng•h/mL) and T _max (4 h) in rats.

Benzeneacetamide, N-(2,4-difluorophenyl)-4-[[2-[4-(ethylsulfonyl)phenyl]acetyl]amino]-2-fluoro-α,α-dimethyl-