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

Benjamin Pelcman; Andrei Sanin; Peter Nilsson; Kiyo No; Wesley Schaal; Sara Öhrman; Christian Krog-Jensen; Pontus Forsell; Anders Hallberg; Mats Larhed; Thomas Boesen; Hasse Kromann; Stine Byskov Vogensen; Thomas Groth; Hans-Erik Claesson

doi:10.1016/j.bmcl.2015.05.004

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. Epub 2015 May 14.

Authors

Affiliations

¹ Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, Uppsala University, Box 574, SE-751 23, Uppsala, Sweden. Electronic address: benjamin.pelcman@orgfarm.uu.se.
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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arachidonate 15-Lipoxygenase / metabolism*
Benzoxazoles / chemistry
Benzoxazoles / pharmacology
Humans
Lipoxygenase Inhibitors / chemistry*
Lipoxygenase Inhibitors / pharmacology*
Pyrazoles / chemistry*
Pyrazoles / pharmacology*
Structure-Activity Relationship
Triazoles / chemistry*
Triazoles / pharmacology*

Substances

Benzoxazoles
Lipoxygenase Inhibitors
Pyrazoles
Triazoles
pyrazole
Arachidonate 15-Lipoxygenase