To explore the chemical space of protein tyrosine phosphatase 1B (PTP1B) inhibitors by changing bis-aromatic amide moiety into aromatic amide moiety, a series of aromatic amide derivatives were designed, synthesized and their biological activities were evaluated against PTP1B and Scr homology-2 domain containing protein tyrosine phosphatase-2 (SHP2). Among them, compound 3c displayed moderate inhibitory activity with IC 50 of (5.13±0.21) μmol/L against PTP1B and showed two times selectivity for other related PTPs. Interestingly, compound 12 [IC 50 =(7.47±1.26) μmol/L] showed moderate inhibitory activity against SHP2 and 2-fold selectivity against PTP1B, T-cell protein tyrosine phosphatase (TCPTP) or Src homology-2 domain containing protein tyrosine phosphatase-1 (SHP1) respectively, and offered a novel scaffold to develop new SHP2 inhibitors.
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