Design, Synthesis and Bioactivity Research of Novel Bipyridine Compounds

doi:10.6023/cjoc202405010

Abstract

Pyridines play an important role in the design of pesticides. Flupyrimin (FLP) is a novel nicotine insecticide with bipyridine structure. Previously, our research found that bipyridine compound N-((6-chloropyridin-3-yl)methyl)-3-methyl- N-(pyridin-2-yl)benzenesulfonamide (3c) had certain insecticidal activity following structural modifications on FLP. In this paper, using 3c as the lead compound, a series of novel bipyridine derivatives were designed and synthesized. Bioactivity assay results revealed that target compounds exhibited some insecticidal and antifungal activities. Among them, N-((6-chloropyridin- 3-yl)methyl)-N-methylpyridin-2-amine (T1) and N-((6-chloropyridin-3-yl)methyl)-N-ethylpyridin-2-amine (T2) showed good insecticidal activity against A. glycines, with LC₅₀ values of 11.04 mg/L and 25.12 mg/L, respectively. N-((6-Chloropyridin-3- yl)methyl)-N-pentylpyridin-2-amine (T5) and N-((6-chloropyridin-3-yl)methyl)-N-hexylpyridin-2-amine (T6) displayed good antifungal activity against B. cinerea with EC₅₀ values of 7.45 mg/L and 10.54 mg/L, respectively. The bee toxicity test results revealed that compound T1 is safe for Apis mellifera. Furthermore, molecular dynamics simulations elucidated the insecticidal mechanism of compound T1, revealing its stable formation of water relaying hydrogen-bond interaction network with key amino acids of AChBP, and a superior binding free energy compared to 3c. This study provides a good significance for exploring the agricultural biological activity of pyridine compounds.

Key words: bipyridine derivatives, insecticidal activity, antifungal activities, low bee toxicity, insecticidal mechanism

Cite this article

Xingxing Lu, Yufan Lin, Huan Xu, Xiaoming Zhang, Xuesheng Li, Yun Ling, Xinling Yang. Design, Synthesis and Bioactivity Research of Novel Bipyridine Compounds[J]. Chinese Journal of Organic Chemistry, 2025, 45(1): 276-285.

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Compd.	200 mg•L^－1	100 mg•L^－1
T1	100	80.96±5.42
T2	95.70±2.72	75.48±5.53
T3	71.32±6.77
T4	82.80±5.93	12.77±2.41
T5	59.14±7.58
T6	81.91±4.10	2.06±2.39
T7	78.49±7.20
T8	95.80±1.33	4.62±0.66
T9	62.72±10.22
T10	95.70±2.72	23.91±0.68
T11	19.61±7.58
T12	3.92±3.60
T13	46.43±1.83	37.84±2.19
T14	79.70±2.24
T15	33.64±6.22
T16	70.85±2.34
3c	72.09±3.14	41.67±6.80
FLP	100	100
Pymetrozine	86.64±7.05	76.13±4.80

Compd.	200 mg•L^－1	100 mg•L^－1
T1	100	80.96±5.42
T2	95.70±2.72	75.48±5.53
T3	71.32±6.77
T4	82.80±5.93	12.77±2.41
T5	59.14±7.58
T6	81.91±4.10	2.06±2.39
T7	78.49±7.20
T8	95.80±1.33	4.62±0.66
T9	62.72±10.22
T10	95.70±2.72	23.91±0.68
T11	19.61±7.58
T12	3.92±3.60
T13	46.43±1.83	37.84±2.19
T14	79.70±2.24
T15	33.64±6.22
T16	70.85±2.34
3c	72.09±3.14	41.67±6.80
FLP	100	100
Pymetrozine	86.64±7.05	76.13±4.80

Compd.	y=ax＋b	LC₅₀/ (mg•L^－1)	95% confiden- ce interval	r
T1	y=1.17x－1.23	11.04	6.38~15.65	0.98
T2	y=0.74x－1.00	25.12	16.97~35.77	0.99
3c	y=1.85x－3.71	102.38	87.35~123.14	0.97
Pymetrozine	y=0.70x－0.54	5.85	2.51~9.78	0.98
FLP	y=0.84x＋0.61	0.20	0.12~0.29	0.98

Compd.	y=ax＋b	LC₅₀/ (mg•L^－1)	95% confiden- ce interval	r
T1	y=1.17x－1.23	11.04	6.38~15.65	0.98
T2	y=0.74x－1.00	25.12	16.97~35.77	0.99
3c	y=1.85x－3.71	102.38	87.35~123.14	0.97
Pymetrozine	y=0.70x－0.54	5.85	2.51~9.78	0.98
FLP	y=0.84x＋0.61	0.20	0.12~0.29	0.98

Compd.	Pythium aphanidermatum	Magnaporthe oryzae	Valsa mali	Botrytis cinerea	Phytophthora capsici
T1	7.42±3.24	19.62±1.48	8.42±0.74	45.65±2.91	8.03±0
T2	16.79±0.65	25.77±0.33	6.57±1.32	47.39±1.43	14.72±0.84
T3	49.03±0.75	31.15±0.33	2.88±0.61	44.35±0.87	32.69±0.36
T4	77.51±1.84	43.85±1.92	9.53±1.68	93.48±0.38	45.65±1.25
T5	52.77±4.90	70.38±4.19	16.54±1.11	100	34.78±0.84
T6	11.54±1.91	64.23±2.39	38.70±1.11	91.30±0	14.30±0.36
T7	63.27±2.02	27.69±0.54	9.16±1.11	40.87±0.61	41.47±0
T8	63.27±0.65	32.69±3.28	15.07±1.85	40.00±1.44	49.83±0
T9	35.53±1.50	31.92±0.64	26.14±5.17	47.83±2.13	50.25±0.36
T10	7.05±1.59	45.38±1.15	49.04±0.64	60.00±0.61	44.40±0.36
T11	3.30±0.65	23.85±0.38	22.82±0.32	38.70±5.08	16.81±0.36
T12	5.55±1.91	36.15±1.28	30.21±1.09	50.00±0.38	23.49±0.69
T13	40.78±2.73	40.00±1.44	32.42±0.61	46.09±0.87	31.86±0.36
T14	38.91±5.26	20.38±1.00	14.33±0	46.09±0.87	17.22±1.25
T15	25.04±5.00	31.15±3.66	6.20±1.11	40.00±0.75	18.06±0.59
T16	40.40±3.53	78.46±3.88	36.85±2.05	46.96±0.75	33.95±0.42
3c	13.97±0.83	54.02±0.50	52.86±0.65	47.66±0.75	25.30±0.75
Pyraclostrobin	100	100	100	24.35±1.30	4.68±0
Prothioconazole	57.77±1.48	100	100	100	66.76±1.12

新型双吡啶类化合物的设计、合成及生物活性研究