Design and synthesis of biphenyl and biphenyl ether inhibitors of sulfatases.

نویسندگان

  • Tristan Reuillon
  • Sari F Alhasan
  • Gary S Beale
  • Annalisa Bertoli
  • Alfie Brennan
  • Celine Cano
  • Helen L Reeves
  • David R Newell
  • Bernard T Golding
  • Duncan C Miller
  • Roger J Griffin
چکیده

Inhibitors of sulfatase-2 are putative anticancer agents, but the discovery of potent small molecules targeting this enzyme has proved challenging. Based on molecular modelling, two series of sulfatase-2 inhibitors have been developed with biphenyl and biphenyl ether scaffolds judiciously substituted with sulfamate, carboxylate and other polar groups (e.g. amino). Inhibition of aryl sulfatase A and B was also determined. The biphenyl ether derivatives were less selective for sulfatase-2 over aryl sulfatase B than the biphenyl series. All biphenyl ether derivatives inhibited aryl sulfatase A, whereas only amino derivatives inhibited aryl sulfatase B significantly. In the biphenyl series few derivatives exhibited activity against aryl sulfatase B. The trichloroethylsulfamate group was identified as a new pharmacophore enabling potent inhibition of all of the sulfatases studied.

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عنوان ژورنال:
  • Chemical science

دوره 7 4  شماره 

صفحات  -

تاریخ انتشار 2016