Aprocitentan

一种内皮素A（ETA）和内皮素B（ETB）受体双重拮抗剂，也是马西腾坦（Macitentan）的活性代谢产物；在人肺动脉平滑肌细胞（HPASMCs）中抑制内皮素-1（ET-1）诱导的细胞内钙升高（IC50=14nM），在分离的大鼠主动脉环中抑制ET-1诱导的收缩（针对ETA受体的pA2=6.7），以及在分离的大鼠气管环中抑制沙拉夫毒素S6c诱导的收缩（针对ETB受体的pKB=5.5）；在10µM和100µM浓度下减少ET-1诱导的分离的人类皮肤成纤维细胞增殖；在正常血压大鼠中增加血浆ET-1浓度，并在DOCA盐诱导的高血压大鼠中以10-300mg/kg剂量给药时降低平均动脉压（MAP）。A dual ETA and ETB receptor antagonist and an active metabolite of macitentan; inhibits ET-1- induced increases in intracellular calcium in HPASMCs (IC50 = 14 nM), ET-1-induced contractions in isolated rat aortic rings (pA2 = 6.7 for ETA), and sarafotoxin S6c-induced contractions of isolated rat tracheal rings (pKB = 5.5 for ETB); reduces ET-1-induced increases in proliferation of isolated human skin fibroblasts at 10 and 100 µM; increases plasma ET-1 concentrations in normotensive rats and decreases MAP in DOCA-salt hypertensive rats at 10-300 mg/kg.分子式C16H14Br2N6O4S分子量546.2O=S(N)(NC1=NC=NC(OCCOC2=NC=C(C=N2)Br)=C1C3=CC=C(C=C3)Br)=O