Design, synthesis and evaluation of novel 3,5-disubstituted benzamide derivatives as allosteric glucokinase activators

Table 1 Physicochemical properties and GK activity of the synthesized 3,5-disubstituted benzamide derivatives

Compound	R	Molecular Formula	M. Pt. (°C)	R ^a_f	% Yield	GK activity^b
5a	–C₆H₅	C₁₇H₁₃N₅O₅S	140–142	0.62	56	1.43 ± 0.06
5b	2-ClC₆H₄–	C₁₇H₁₂ClN₅O₅S	157–158	0.37	63	1.74 ± 0.08
5c	3-ClC₆H₄–	C₁₇H₁₂ClN₅O₅S	161–162	0.53	62	1.34 ± 0.05
5d	4-ClC₆H₄–	C₁₇H₁₂ClN₅O₅S	165–167	0.57	61	1.36 ± 0.03
5e	2-NO₂C₆H₄–	C₁₇H₁₂N₆O₇S	155–156	0.69	68	1.49 ± 0.07
5f	3-NO₂C₆H₄–	C₁₇H₁₂N₆O₇S	158–160	0.72	65	1.89 ± 0.06
5g	4-NO₂C₆H₄–	C₁₇H₁₂N₆O₇S	152–154	0.69	74	1.65 ± 0.04
5h	–CH₂C₆H₅	C₁₈H₁₅N₅O₅S	138–140	0.62	76	1.20 ± 0.06
5i	–C₂H₅	C₁₃H₁₃N₅O₅S	147–148	0.56	69	1.68 ± 0.04
6a	–C₆H₅	C₁₆H₁₂N₄O₅S₂	154–160	0.75	76	1.65 ± 0.06
6b	2-ClC₆H₄–	C₁₆H₁₁ClN₄O₅S₂	181–182	0.56	66	1.59 ± 0.08
6c	3-ClC₆H₄–	C₁₆H₁₁ClN₄O₅S₂	189–191	0.64	59	2.11 ± 0.05
6d	4-ClC₆H₄–	C₁₆H₁₁ClN₄O₅S₂	185–186	0.62	77	1.55 ± 0.08
6e	2-NO₂C₆H₄–	C₁₆H₁₁N₅O₇S₂	180–182	0.38	72	2.11 ± 0.09
6f	3-NO₂C₆H₄–	C₁₆H₁₁N₅O₇S₂	176–177	0.48	68	1.37 ± 0.07
6g	4-NO₂C₆H₄–	C₁₆H₁₁N₅O₇S₂	182–183	0.42	59	1.24 ± 0.08
6h	–CH₂C₆H₅	C₁₇H₁₄N₄O₅S₂	164–166	0.55	53	1.99 ± 0.07
6i	–C₂H₅	C₁₂H₁₂N₄O₅S₂	162–163	0.58	48	1.08 ± 0.09

^aTLC mobile phase: Benzene: Ethyl acetate (7:3)
^bAll the values are mean of three measurements ± SD (as GK fold activation at 10 µM concentration compared to control i.e., DMSO only)

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