Design, Synthesis and Evaluation of Substituted 3-(1, 4-Diazepanyl)-Methyl-Phenyl-Sulphonamides as Potent 5-HT6 Antagonists in Cognitive Disorders

Table 2: 5-HT₆R novel ligands in silico binding affinities (Ki) nM and fitness scores^a.

Ligands	R¹	R²	Fitness	Ki (nM)	Ligands	R¹	R²	Fitness	Ki (nM)
10a	Ph	H	2.38	18.85	10g	i-Pr	H	2.02	08.71
10b	4-F Ph	H	2.41	20.34	10h	Me	H	2.09	17.41
10c	4-Cl Ph	H	2.41	14.46	10i	4-Br Ph	H	2.27	14.89
10d	4-Me Ph	H	2.41	10.00	10j	4-F Ph	CH₃	2.10	24.73
10e	4-OCH₃ Ph	H	2.04	08.06	10k	4-Cl Ph	CH₃	2.09	19.95
10f	Et	H	2.33	07.11	10l	4-Me Ph	CH₃	2.10	17.65

^aThe Ki values were determined through ligand based pharmacophore model development in silico screening using PHASE-Schrodinger software. Ph = phenyl, i-Pr = isopropyl, Me = methyl, Et = ethyl.