Molecular structures and binding affinities of the tested compounds towards 5-HT₆R.

General structure	No.	L	5-HT6R Ki [nM]a
	1a	–SO2–	1 ± 0.2
	1b	–CO–	1280 ± 231
	1c	–CH2–	51 ± 7
	2a	–SO2–	11 ± 2
	2b	–CO–	44 ± 8
	2c	–CH2–	23 ± 5
	3a	–SO2–	4 ± 1
	3b	–CO–	187 ± 22
	3c	–CH2–	18 ± 3
	4a	–SO2–	1 ± 0.3
	4b	–CO–	2204 ± 189
	4c	–CH2–	24 ± 5

^aTo test the selectivity profile of presented ligands towards 5-HT₆R, the binding affinities towards 5-HT_1AR, 5-HT₇R and D₂R were additionally determined for selected compounds. For experimental details and measured values, see Section S1 in the ESI.