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17. Semi-automatic patch clamp method was used using Port-A- Patch (from Nanion technologies,
Germany). HEK293 cells stably expressing hERG potassium channels. 0.1% DMSO in extracellular
HEPES buffer was used as the vehicle. Assay conditions were room temperature and the compound
addition was done manually. Aspirin at 10M concentration was used as a negative control. Cisapride or
verapamil at 1M concentration were used as positive controls.
18. TPSA
and
cLogP
were
calculated
using
ACD/ToxSuite
2.95
ACD/Labs.
19. The description of the synthesis and the spectroscopic data has been described in WO2017180818.
20. pKa were calculated using ACD/ToxSuite 2.95 ACD/Labs. Comparable pKa numbers were obtained
21. Rampe, D.; Wibble, B.; Brown, A. M.; Dage, R. C. Effects of terfenadine and its metabolites on a
delayed rectifier K+ channel cloned from human heart. Mol. Pharmacol. 1993, 44, 1240-1245.
22. Nikolov, N. G.; Dybdahl, M.; Jónsdóttir, S. Ó.; Wedebye, E. B. “hERG blocking potential of acids and
zwitterions characterized by three thresholds for acidity, size and reactivity” Bioorg. Med. Chem. 2014,
22, 6004-6013.
23. Yajuan, X.; Xin, L.; Zhiyuan, L. “A Comparison of the Performance and Application Differences
between Manual and Automated Patch-Clamp Techniques” Current Chemical Genomics, 2012, 6, 87-92.
24. In the transactivation assay CV-1 cells are transfected with a PPAR ligand binding domain fused to a
GAL4 promoter to generate a hormone-inducible activator. A test ligand is added and activity is
measured in a luciferase assay. See WO2016057660 for further details.
25. All the animal experiments were carried out as per the guidelines of the Committee for the Purpose of
Control and Supervision of Experiments on Animals (CPCSEA), Government of India and approved by
the Institutional Animal Ethics Committee (IAEC), Aurigene Discovery Technologies Ltd,, Bengaluru,
India.
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