1449473-97-5
1449473-97-5 结构式
基本信息
1H-Benzimidazole-2-propanamide, β-amino-6-(1,1-dimethylethyl)-α-methyl-, (αR,βS)-
(2R,3S)-3-amino-3-(5-(tert-butyl) -1H-benzo[d]imidazol-2-yl)-2- methylpropanamide
物理化学性质
常见问题列表
PF-06305591制备如下：将[（1S）-3-氨基-1-（5-叔丁基-1H-苯并咪唑-2-基）-2-甲基-3-氧丙基]氨基甲酸叔丁酯溶液（3.07g）在DCM（50mL）和TFA（10mL）中中搅拌3小时。加入饱和NaHCO3水溶液（100mL），产物用2-MeTHF（4×100mL）萃取。合并有机层，用盐水洗涤，经Na2SO4干燥并真空浓缩。使用反相柱色谱法纯化残余物，用0-40％乙腈的水溶液洗脱。将得到的固体在50℃下溶于MeCN（40mL）中，并在使溶液冷却之前添加甲醇。收集得到的白色沉淀，干燥，并进一步用EtOAc（5mL）研磨两次，得到白色固体PF-06305591。
IC50: 15 nM (NaV1.8).
PF-06305591 (compound 9) has a highly attractive profile with respect to NaV selectivity, hERG activity, passive permeability and in vitro metabolic stability.
PF-06305591 (compound 9) has good rat bioavailability. PF-06305591 offers the possibility of investigating higher IC 50 multiples of Nav1.8 blockade in the clinic, and therefore a more thorough evaluation of the role of NaV1.8 in the treatment of pain.