3-Substituted pyrazoles and 4-substituted triazoles as inhibitors of human 15-lipoxygenase-1

  • Bioorg Med Chem Lett. 2015 Aug 1;25(15):3024-9. doi: 10.1016/j.bmcl.2015.05.004.
Benjamin Pelcman  1 ,  Andrei Sanin  2 ,  Peter Nilsson  3 ,  Kiyo No  2 ,  Wesley Schaal  3 ,  Sara Öhrman  2 ,  Christian Krog-Jensen  2 ,  Pontus Forsell  2 ,  Anders Hallberg  4 ,  Mats Larhed  4 ,  Thomas Boesen  5 ,  Hasse Kromann  5 ,  Stine Byskov Vogensen  5 ,  Thomas Groth  5 ,  Hans-Erik Claesson  6
Affiliations
  • 1. Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-751 23, Uppsala, Sweden. Electronic address: [email protected].
  • 2. Biolipox AB, Berzelius väg 3, SE-171 65 Solna, Sweden.
  • 3. Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-751 23, Uppsala, Sweden; Biolipox AB, Berzelius väg 3, SE-171 65 Solna, Sweden.
  • 4. Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-751 23, Uppsala, Sweden.
  • 5. MedChem ApS, Fruebjergvej 3, DK-2100 Copenhagen, Denmark.
  • 6. Biolipox AB, Berzelius väg 3, SE-171 65 Solna, Sweden; Department of Medicine, Building A3:02, Karolinska University Hospital Solna and Karolinska Institutet, SE-171 76 Stockholm, Sweden.
PMID: 26037322 DOI: 10.1016/j.bmcl.2015.05.004
Abstract

Investigation of 1N-substituted pyrazole-3-carboxanilides as 15-lipoxygenase-1 (15-LOX-1) inhibitors demonstrated that the 1N-substituent was not essential for activity or selectivity. Additional halogen substituents on the pyrazole ring, however, increased activity. Further development led to triazole-4-carboxanilides and 2-(3-pyrazolyl) benzoxazoles, which are potent and selective 15-LOX-1 inhibitors.

Keywords
15-Lipoxygenase; Arachidonic acid; Benzoxazole; Inhibitors; Pyrazole; Triazole.
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