Design, synthesis and evaluation of novel 2-amino-3-(naphth-2-yl)propanoic acid derivatives as potent inhibitors of platelet aggregation.
Based upon LX2421, a previously identified antiplatelet aggregation agent, a series of novel 2-amino-3-(naphth-2-yl)propanoic acid derivatives were designed, synthesized and evaluated. Among them, compounds LX14 and LX25 were identified as promising antiplatelet aggregation agents. The in vitro biologic study demonstrated that LX14 can block platelet aggregation induced by four different inducers and displays comparable potency in inhibiting GPIIb/IIIa receptor in comparison with Tirofiban. In addition, LX14 has much lower risk of bleeding than Tirofiban and shows significant antithrombotic activity in vivo. Taking together, the results indicated that LX14 is a promising GPIIb/IIIa receptor antagonist against platelet aggregation worthy of further evaluation.
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Zhouling
Z
Xie
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Benimana
B
Oscar
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Lulu
L
Zhao
School of Life Science & Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Xue
X
Ding
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Chen
C
Cao
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Sen
S
Feng
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Han
H
Li
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Chen
C
Pan
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Ziyi
Z
Bian
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Yang
Y
Li
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Weijun
W
Wang
School of Life Science & Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: yikong668@163.com.
Yi
Y
Kong
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China. Electronic address: zhiyuli@cpu.edu.cn.
Zhiyu
Z
Li
D015195:Drug Design; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011422:Propionates / Q000138:chemical synthesis / Q000494:pharmacology*; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011422:Propionates
Antiplatelet aggregation; Antithrombotic activity; Bleeding risk; GPIIb/IIIa receptor; Inhibitor; Naphthalene derivatives