. Author manuscript; available in PMC: 2020 Aug 15.

Published in final edited form as: Bioorg Med Chem Lett. 2019 Jun 20;29(16):2254–2258. doi: 10.1016/j.bmcl.2019.06.033

Table1.

LAT1 trans-stimulation and cis-inhibition cell assay activity for N- and C-linked triazoles 7a-e and 11d-e.



Compound^a	R	Regioisomer	Relative %Efflux^b	% Inhibition^c	IC₅₀ (μM)^d
7a	H	N	82	58	160 ± 27
7b	Ph	N	37	13	>1000
7c	CH₂OH	N	57	14	>1000
7d	Me	N	70	38	440 ± 190
11d	Me	C	63	20	>1000
7e	Bn	N	49	−6	ND^e
11e	Bn	C	43	−19	ND^e

Cell assay data was obtained at least in triplicate (24-well poly-D plate configuration) in each condition. All compounds above are single enantiomers of L configuration.

Compounds were tested at 200 μM for their ability to cause efflux (fmol/min) of [³H]-gabapentin from pre-loaded HEK-hLAT1 cells. Efflux of [³H]-gabapentin was calculated at 3 min after adding test compound. %Efflux was normalized relative to L-Phe (18), which had an efflux rate of 2.7 ± 0.3 fmol/min, from an average of seven experiments.

Compounds were tested at 200 μM for their ability to inhibit uptake of [³H]-gabapentin into HEK-hLAT1 cells. Data are presented as % inhibition relative to background signal in the absence of a test compound.

For IC₅₀ determinations, varying concentrations of each compound were added, from 0.1 μM to 500 μM. IC₅₀ and standard deviation of each compound was calculated by GraphPad Prism version 5.0. %[³H]-Gabapentin uptake at each concentration was normalized relative to %inhibition by BCH³¹ at 2 mM, which was set to 100% inhibition.

Not determined.