1146699-66-2
1146699-66-2 结构式
基本信息
Γ-SECRETASE抑制剂(BMS-708163)
(2R)-2-[N-[(4-氯苯基)磺酰基]-N-[2-氟-4-(1,2,4-恶二唑-3-基)苄基]氨基]-5,5,5-三氟戊酰胺
BMS-708163
Avagacestat
BMS-708163, >=98%
BMS708163
BMS 708163
BMS-708163 (Avagacestat)
Avagacestat (BMS-708163)
BMS708163
BMS 708163
AVAGACESTAT
(R)-2-(4-Chloro-N-(2-fluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-phenylsulfonamido)-5,5,5-trifluoro
(R)-2-(4-Chloro-N-(2-fluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-phenylsulfonamido)-5,5,5-trifluoropen
物理化学性质
制备方法
![Pentanamide, 2-[[(4-chlorophenyl)sulfonyl][[2-fluoro-4-[(hydroxyamino)iminomethyl]phenyl]methyl]amino]-5,5,5-trifluoro-, (2R)-](/CAS/20210305/GIF/1146699-70-8.gif)
1146699-70-8
122-51-0
1146699-66-2
步骤C. 将(R)-2-(4-氯-N-(2-氟-4-(N'-羟基甲脒基)苄基)-苯磺酰氨基)-5,5,5-三氟戊酰胺（246g）加入反应器中，随后加入干燥的乙腈（509mL）、原甲酸三乙酯（120mL）和三氟乙酸（7mL）。将反应混合物加热至40-50℃，并通过HPLC监测反应进度，直至起始原料的相对面积百分比（AP）低于0.15。反应完成后，一次性加入甲醇（1.48L），然后加入水（1.034L），保持反应体系温度在45-50℃。随后将反应混合物冷却至15-20℃，过滤收集固体。用乙腈:甲醇:水（2:6:5，v/v/v）的混合溶剂洗涤滤饼，并在50-60℃下真空干燥，得到(2R)-2-[N-[(4-氯苯基)磺酰基]-N-[2-氟-4-(1,2,4-恶二唑-3-基)苄基]氨基]-5,5,5-三氟戊酰胺，为白色固体（228g，收率90%）。 1H NMR (CDCl3, 300MHz) δ: 1.40-1.58 (m, 1H), 1.75-1.90 (m, 1H), 1.92-2.07 (m, 1H), 2.10-2.26 (m, 1H), 4.37 (dd, J = 8.67, 6.22Hz, 1H), 4.48 (d, J = 15.64Hz, 1H), 4.64 (d, J = 15.82Hz, 1H), 5.54 (s, 1H), 6.33 (s, 1H), 7.44-7.54 (m, 2H), 7.62 (t, J = 7.72Hz, 1H), 7.68-7.76 (m, 3H), 7.85 (dd, J = 7.91, 1.51Hz, 1H), 8.76 (s, 1H). 13C NMR (DMSO-d6, 75MHz) δ: 170.34, 167.75, 165.80, 159.64 (d, J = 244.5Hz, 1C), 138.19, 137.64, 131.25 (d, J = 3.75Hz, 1C), 129.31, 129.23, 129.05 (d, J = 14.25Hz, 1C), 126.74 (q, J = 274.5Hz, 1C), 126.91, 126.80, 123.12 (d, J = 3.75Hz, 1C), 113.7 (d, J = 24.0Hz, 1C), 57.92, 41.38 (d, J = 4.5Hz, 1C), 30.04 (d, J = 30.0Hz, 1C), 22.90. 19F NMR (CDCl3, 282MHz) δ: -116.3, -66.5. IR (KBr): 3454, 334, 3286, 2952, 1705, 1432, 1325, 1260, 1167, 1084, 828 cm-1. 元素分析: 计算值 C20H17ClF4N4O4S: C, 46.11; H, 3.29; N, 10.71; S, 6.15; F, 14.58; Cl, 6.80. 实测值: C, 46.06; H, 3.24; N, 10.71; S, 6.25; F, 14.60; Cl, 6.88.
参考文献：
[1] Patent: US2009/111858, 2009, A1. Location in patent: Page/Page column 23
[2] Patent: US2009/111858, 2009, A1. Location in patent: Page/Page column 19-20
[3] ACS Medicinal Chemistry Letters, 2010, vol. 1, # 3, p. 120 - 124
常见问题列表
| Target | Value |
|
γ secretase(Aβ42)
(in H4-8Sw cells) | 0.27 nM |
|
γ secretase(Aβ40)
(in H4-8Sw cells) | 0.3 nM |
BMS-708163 抑制Notch 过程时显示出低选择性。