Synthesis of N-(6-(4-(Piperazin-1-yl)phenoxy)pyridin-3-yl)benzenesulfonamide Derivatives for the Treatment of Metabolic Syndrome

Table 1

Compounds with in vitro biological activity.

Compound number	R	Adipogenesis 𝐸max (%)^a	PPARγ agonism 𝐸max (%)^b
6	2,4-Dichlorobenzene	90	36.4
7	3,4-Dimethoxybenzene	67	9.12
8	2,5-Dimethoxybenzene	72	18.5
9	2-Thiophene	69	11.3
10	3,4-Dichlorobenzene	75	19.2
11	4-Methylbenzene	73	17.8
12	4-(Trifluoromethoxy)benzene	89	26.8
13	2,4-Difluorobenzene	81	25.7
14	4-Fluorobenzene	74	9.4
15	Methyl	52	6.5
16	1,2-Dimethyl-1H-imidazole	69	8.2
17	5-Chloro-1,3-dimethyl-1H-pyrazole	69	8.5
18	3,5-Dimethylisoxazole	69	8.5
19	2-Fluoro-4-methylbenzene	78	14.6
20	2,5-Dimethylbenzene	79	22.5
21	8-Quinoline	82	29.3
22	4-Benzonitrile	85	27.6
23	2-Chloro-4-fluorobenzene	85	27.5
24	4-Methoxybenzene	82	25.0
25	2-Chloro-4-(trifluoromethyl)benzene	87	31.7
26	3-Cholobenzene	71	11.2
27	3-(Trifluoromethyl)benzene	76	19.1
28	2-Fluoro-4-chlorobenzene	75	20.9
29	2-Methyl-4-fluorobenzene	65	8.17
30	3-Chloro-4-fluorobenzene	72	16.8
31	4-Chlorobenzene	78	19.3
32	3-Methylbenzene	62	11.4

All values have been generated with a 𝑛=2.
aThe compounds were tested for adipogenic activity in the presence of insulin in 3T3-L1 cells at a concentration of 20 µg/mL [12]. The adipogenic activity in the presence of potent PPARγ full agonist, rosiglitazone, at 1 µM was defined as 100%, and the maximum adipogenic activity in the presence of the test compound was defined as 𝐸_max (%).
bThe compounds were tested for agonist activity on PPAR in transiently transfected HEK 293 cells at a concentration of 10 µM [13]. The transcriptional activity in the presence of rosiglitazone (1 µM) was defined as 100%; the maximum transcriptional activity in the presence of the test compound was defined as 𝐸_max (%).