- Synthesis and biological evaluation of (±)-3-(2-(2-fluorobenzyloxy) naphthalen-6-yl)-2-aminopropanoic acid derivatives as novel PTP1B inhibitors.
Synthesis and biological evaluation of (±)-3-(2-(2-fluorobenzyloxy) naphthalen-6-yl)-2-aminopropanoic acid derivatives as novel PTP1B inhibitors.
European journal of medicinal chemistry (2011-06-18)
Liang-Peng Sun, Qiang Shen, Hong-Hua Piao, Wei-Ping Ma, Li-Xin Gao, Wei Zhang, Fa-Jun Nan, Jia Li, Hu-Ri Piao
PMID21680062
ABSTRACT
A series of novel nonphosphonate-based pTyr mimetics comprised (±)-3-(2-(2-fluorobenzyloxy)naphthalen-6-yl)-2-aminopropanoic acid derivatives were identified as reversible and competitive PTP1B inhibitors via a structure-based design approach. Among the compounds studied, 12h was found to have the best in vitro inhibition activity against PTP1B (IC(50) = 1.25 ± 0.24 μM) and the best selectivity (3-fold) between PTP1B and TCPTP. These results should provide suitable druglike lead compounds for the design of inhibitors of PTP1B as well as other PTPs.