Synthesis of 5-Phenyl-1,3,4-thiadiazole Derivatives and Their Biochemical Evaluation against Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase 1 (SHP1)

The Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) is a convergent node for oncogenic cell-signaling cascades. Consequently, SHP1 represents a potential target for drug development in cancer treatment. Meanwhile only countable SHP1 inhibitors have been reported. A new type of SHP1 inhibitors with 5-phenyl-1,3,4-thiadiazole scaffold was developed. The representative compound 5b exhibited SHP1 inhibitory activity with IC50 of (1.33 +/- 0.16) mu mol/L, exhibited about 2-fold selectivity for SHP1 over SHP2, and had no detectable activity against PTP1B and TCPTP, and offered a novel scaffold to develop new SHP1 inhibitors.