Study on the Synthesis and Fungicidal Activity of 1-Azolyl-1,1- diarylmethanes Containing Pyridine Ring

doi:10.6023/cjoc202506035

Abstract

To investigate pyridine influence on azole fungicides, 24 novel pyridine-containing 1-azolyl-1,1-diarylmethane derivatives were synthesized using bifonazole as the lead compound and pyridinyl diaryl ketone molecules plug-in as the raw materials. Their antifungal activities against 10 plant pathogenic fungi were evaluated in vitro. Several compounds exhibited promising inhibitory effects, particularly 4-([1,1'-biphenyl]-4-yl(1H-1,2,4-triazol-1-yl)methyl)-2-chloropyridine (I-12), 1-((4- (tert-butyl)phenyl)(3-chlorophenyl)methyl)-1H-1,2,4-triazole (I-21) and 4-((4-(tert-butyl)phenyl)(1H-imidazol-1-yl)methyl)- 2-chloropyridine (I-23), which showed significant efficacy against Sclerotinia sclerotiorum, Fusarium graminearum, Botrytis cinerea and Pythium aphanidermatum. Notably, compound I-23 showed equivalent efficacy (EC₅₀=14.03 mg/L) to bifonazole (14.87 mg/L) against P. aphanidermatum. Structure-activity relationship analysis revealed that imidazole-substituted derivatives generally exhibited higher activity, where bulky substituents on phenyl rings and increased hydrophobicity positively influenced the fungicidal effects. Molecular docking studies further elucidated the possible binding mechanisms between these compounds and target proteins.

Key words: fungicide, 1-azolyl-1,1-diarylmethanes, fungicidal activity, structure-activity relationship, molecular docking

Cite this article

Hong Sai, Yin Fahong, Chen Minghui, Fu Bin, Xiao Yumei, Qin Zhaohai. Study on the Synthesis and Fungicidal Activity of 1-Azolyl-1,1- diarylmethanes Containing Pyridine Ring[J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 106-117.

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References 38

[1]	Song H.; Wang S.; Cai Q.; Chen J. J. Heterocycl. Chem. 2024, 61, 365.
[2]	Howard K. C.; Dennis E. K.; Watt D. S.; Garneau-Tsodikova S. Chem. Soc. Rev. 2020, 49, 2426.
[3]	Sobel J. D.; Nyirjesy P. Future Microbiol. 2021, 16, 1453.
[4]	Li C.; Liu C. Environ. Pollut. 2022, 307, 119553.
[5]	Li S.; Sun Q.; Wu Q.; Gui W.; Zhu G.; Daniel S. Environ. Pollut. 2019, 249, 1049.
[6]	Vinggaard A. M.; Hass U.; Dalgaard M.; Andersen H. R.; Bonefeld-JØRgensen E. V. A.; Christiansen S.; Laier P.; Poulsen M. E. Int. J. Androl. 2006, 29, 186.
[7]	Dufourc E. J. J. Chem. Biol. 2008, 1, 63.
[8]	Lepesheva G. I.; Waterman M. R. Biochim. Biophys. Acta, Proteins Proteomics 2011, 1814, 88.
[9]	Ragsdale N. N.; Sisler H. D. Pestic. Biochem. Physiol. 1973, 3, 20.
[10]	Lepesheva G. I.; Hargrove T. Y.; Anderson S.; Kleshchenko Y.; Furtak V.; Wawrzak Z.; Villalta F.; Waterman M. R. J. Biol. Chem. 2010, 285, 25582.
[11]	Lepesheva G. I.; Waterman M. R. Biochim. Biophys. Acta, Gen. Subj. 2007, 1770, 467.
[12]	Yan Y.; Bao A.; Wang Y.; Xie X.; Wang D.; Deng Z.; Wang X.; Cheng W.; Li W.; Zhang X.; Tang X. J. Agric. Food Chem. 2024, 72, 9424.
[13]	Zhang R.; Wang Y.; Wu A.; Wang J.; Zhang J. Eur. J. Med. Chem. 2023, 259, 115658.
[14]	Köller W.; Wubben J. P. Pestic. Sci. 1989, 26, 133.
[15]	Zakharychev V. V.; Martsynkevich A. M. Adv. Agrochem 2025, 4, 30.
[16]	Monk B. C.; Sagatova A. A.; Hosseini P.; Ruma Y. N.; Wilson R. K.; Keniya M. V. Biochim. Biophys. Acta, Proteins Proteomics 2020, 1868, 140206.
[17]	Sánchez-Torres P.; Tuset J. J. Postharvest Biol. Technol. 2011, 59, 159.
[18]	Zhou Y.; Yu J.; Pan X.; Yu M.; Du Y.; Qi Z.; Zhang R.; Song T.; Yin X.; Liu Y. Pestic. Biochem. Physiol. 2019, 153, 144.
[19]	Bolton M. D.; Ebert M. K.; Faino L.; Rivera-Varas V.; de Jonge R.; Van de Peer Y.; Thomma B. P. H. J.; Secor G. A. Fungal Genet. Biol. 2016, 92, 1.
[20]	Yan Y.; Xie X.; Jiang W.; Bao A.; Deng Z.; Wang D.; Wang J.; Li W.; Tang X. J. Agric. Food Chem. 2024, 72, 12260.
[21]	Liu Y.; Ma T.; Dong Y.; Mao C.; Wu J.; Zhang C. Pestic. Biochem. Physiol. 2022, 186, 105169.
[22]	Xie X.; Wang J.; Bao A.; Deng Z.; Wang D.; Chen W.; Jiang W.; Li W.; Tang X.; Yan Y. Pest Manage. Sci. 2025, 81, 1953.
[23]	Wang D.; Zhang T.; Deng Z.; Xie X.; Bao A.; Chen W.; Li W.; Li S.; Tang X.; Yan Y. J. Agric. Food Chem. 2025, 73, 2332.
[24]	Bao A.; Jiang W.; Xie X.; Wang D.; Deng Z.; Wang J.; Li W.; Tang X.; Yan Y. J. Med. Chem. 2024, 67, 7954.
[25]	Wang J.; Shi H.; Lu A. J. Fungi 2024, 10, 160.
[26]	Lackner T. E.; Clissold S. P. Drugs 1989, 38, 204.
[27]	Faergemann J. Mycoses 1989, 32, 309.
[28]	Berg D.; Plempel M. Dermatologica 2009, 169, 3.
[29]	Che C.; Yang D.; Wan C.; Wang J.; Liu X.; Zhao F.; Qin Z. Chin. J. Pestic. Sci. 2017, 19, 533 (in Chinese).
	(车传亮, 杨冬燕, 万川, 王家尧, 刘雪莲, 赵峰海, 覃兆海, 农药学学报, 2017, 19, 533.)
[30]	Mu C.; Yuan H.; Li N.; Fu B.; Xiao Y.; Ma Y.; Qi S.; Qin Z. Chem. J. Chin. Univ. 2007, 1902 (in Chinese).
	(慕长炜, 袁会珠, 李楠, 傅滨, 肖玉梅, 马永强, 齐淑华, 覃兆海, 高等学校化学学报, 2007, 1902.)
[31]	Yan X.; Qin W.; Sun L.; Qi S.; Yang D.; Qin Z.; Yuan H. J. Agric. Food Chem. 2010, 58, 2720.
[32]	Xiao Y.; Yang X.; Li B.; Yuan H.; Wan S.; Xu Y.; Qin Z. Molecules 2011, 16, 8945.
[33]	Xiang L.; Zhang L.; Wu Q.; Xu Z.; Li J.; Du X.; Qin Z. Pest Manage. Sci. 2020, 76, 2058.
[34]	Bevan T. W.; Francis-Taylor J.; Wong H.; Northcote P. T.; Harvey J. E. Tetrahedron 2018, 74, 2942.
[35]	Srivastava P.; Razi S. S.; Ali R.; Gupta R. C.; Yadav S. S.; Narayan G.; Misra A. Anal. Chem. 2014, 86, 8693.
[36]	Delcaillau T.; Boehm P.; Morandi B. J. Am. Chem. Soc. 2021, 143, 3723.
[37]	Sun J. L.; Mu W. Pesticide Science Experimental Techniques and Guidance, Chemical Industry Press, Beijing, 2009 (in Chinese).
	(孙家隆, 慕卫, 农药实验技术与指导, 化学工业出版社, 北京, 2009.)
[38]	Trott O.; Olson A. J. J. Comput. Chem. 2010, 31, 455.

Compd.		Inhibition rate/(%, 50 mg/L)										MIR^c%
Compd.	Log P^a	R. solani^b	S. sclerotiorum^b	P. capsici^b	C. gloeosporioides^b	F. oxysporum^b	F. graminearum^b	F. fujikuroi^b	P. aphanidermatum^b	B. cinerea^b	P. oryzae^b	MIR^c%
I-1	3.42	22.15±2.51	16.80±2.08	8.74±0.93	18.68±0.54	12.18±0.84	45.05±0.79	25.77±2.43	17.37±1.24	28.14±1.89	50.10±2.15	24.5
I-2	3.84	35.64±2.64	29.23±1.98	26.81±0.73	33.50±0.36	26.98±0.42	53.91±1.42	37.99±3.02	31.75±0.35	45.08±1.92	44.66±1.31	36.56
I-3	4.25	57.46±1.06	41.00±0.60	55.71±0.20	43.34±0.74	36.92±0.56	57.43±0.34	38.22±2.22	33.88±1.22	63.22±2.16	49.28±2.33	47.65
I-4	4.17	60.46±0.43	32.10±1.71	44.76±0.35	43.69±0.41	39.11±2.22	57.31±1.42	51.48±1.40	39.77±0.54	45.65±0.52	36.10±0.57	45.04
I-5	5.09	57.57±1.19	43.62±2.67	60.49±0.93	44.64±1.03	41.41±0.63	61.85±1.23	48.02±0.87	42.48±0.41	84.41±2.03	57.84±3.18	54.23
I-6	4.64	63.82±0.87	48.85±0.45	57.23±0.88	44.40±2.05	47.72±0.21	62.76±1.04	55.74±0.69	46.72±0.41	58.42±1.04	21.61±0.29	50.73
I-7	5.05	65.79±2.81	50.16±0.78	57.69±0.35	48.91±0.21	45.05±1.31	76.61±2.39	55.86±0.87	49.08±1.41	68.36±1.04	26.22±3.21	54.37
I-8	3.49	18.75±3.79	17.19±1.18	21.45±0.81	25.56±0.54	20.18±0.42	39.03±1.48	37.76±3.99	33.40±2.84	47.12±2.06	75.46±0.29	33.59
I-9	3.09	3.18±2.74	0.31±0.78	2.80±0.70	12.40±0.54	8.90±0.56	37.78±0.39	33.15±1.60	33.52±1.22	44.18±2.07	34.29±0.49	21.05
I-10	3.76	21.82±2.19	23.99±1.77	31.24±0.88	32.08±0.71	23.70±1.52	42.55±0.39	45.37±1.20	35.29±1.06	39.44±1.41	78.26±0.99	37.37
I-11	4.92	60.20±0.87	54.87±2.08	59.91±1.41	50.57±0.62	37.41±0.36	55.95±0.79	46.52±1.06	53.32±0.61	86.78±3.11	41.04±0.57	54.66
I-12	4.61	64.80±1.51	67.03±0.39	53.15±1.95	53.77±0.36	43.84±0.21	75.25±0.52	51.48±0.20	77.84±0.82	88.25±0.85	82.54±1.03	65.8
I-13	2.80	15.90±1.55	7.12±0.23	0.00	12.87±0.36	8.18±0.21	31.77±0.20	21.39±2.22	15.37±0.41	58.87±3.20	29.02±1.24	20.05
I-14	3.91	26.75±4.06	25.95±0.23	21.45±0.53	31.96±0.21	21.88±1.83	56.18±0.39	30.61±3.73	21.97±0.74	18.42±0.39	51.91±0.57	30.71
I-15	3.91	19.19±2.33	17.32±2.61	18.88±1.05	21.76±0.62	19.46±0.42	31.77±1.29	25.54±3.81	15.49±0.61	55.14±1.09	38.24±1.71	26.28
I-16	3.91	3.29±2.37	8.69±0.82	16.90±1.58	20.46±0.21	15.21±7.31	35.51±1.42	16.55±2.69	12.78±1.14	38.64±1.55	46.64±0.99	21.47
I-17	4.29	52.96±3.47	44.40±0.82	50.70±1.26	39.90±0.62	36.44±1.11	48.23±1.77	48.48±2.42	27.39±0.74	52.09±2.18	28.19±3.02	42.88
I-18	4.64	54.82±1.52	49.63±2.16	53.73±0.73	44.64±1.03	35.10±0.42	49.25±0.59	42.95±1.38	46.49±1.08	66.10±1.89	27.54±1.51	47.03
I-19	5.34	68.75±0.33	65.72±1.59	59.91±1.07	40.61±1.23	61.67±0.76	68.44±1.94	59.77±0.53	48.14±1.47	73.79±2.74	24.74±2.00	57.15
I-20	4.64	41.34±1.55	24.65±0.78	39.42±1.15	28.99±0.21	25.16±1.38	48.00±1.71	31.77±2.22	29.40±0.20	47.29±0.24	23.09±2.00	33.91
I-21	5.63	65.24±1.33	72.53±1.04	45.34±1.41	46.42±0.21	31.59±1.67	70.59±0.20	42.25±0.35	32.11±2.55	88.93±0.39	43.02±0.57	53.8
I-22	3.07	48.03±3.01	0.00	24.94±1.01	33.14±1.23	12.54±2.00	56.18±0.39	34.65±1.04	18.79±2.13	0.00	74.80±1.31	30.31
I-23	4.28	66.01±1.00	11.43±0.45	87.18±0.73	52.11±0.54	28.68±1.89	79.11±2.58	52.51±1.00	84.21±0.82	49.04±3.43	53.15±2.45	56.34
I-24	3.55	40.24±2.64	1.88±0.78	34.73±2.27	40.02±0.21	16.06±0.76	61.06±0.52	55.62±0.53	8.06±0.71	6.67±0.85	71.34±1.48	33.57
Bifonazole	4.69	75.44±4.49	90.71±1.59	96.39±1.58	94.90±0.21	91.51±1.17	92.28±0.86	80.06±0.20	72.87±0.38	100.00	100.00	89.42

Compd.		Inhibition rate/(%, 50 mg/L)										MIR^c%
Compd.	Log P^a	R. solani^b	S. sclerotiorum^b	P. capsici^b	C. gloeosporioides^b	F. oxysporum^b	F. graminearum^b	F. fujikuroi^b	P. aphanidermatum^b	B. cinerea^b	P. oryzae^b	MIR^c%
I-1	3.42	22.15±2.51	16.80±2.08	8.74±0.93	18.68±0.54	12.18±0.84	45.05±0.79	25.77±2.43	17.37±1.24	28.14±1.89	50.10±2.15	24.5
I-2	3.84	35.64±2.64	29.23±1.98	26.81±0.73	33.50±0.36	26.98±0.42	53.91±1.42	37.99±3.02	31.75±0.35	45.08±1.92	44.66±1.31	36.56
I-3	4.25	57.46±1.06	41.00±0.60	55.71±0.20	43.34±0.74	36.92±0.56	57.43±0.34	38.22±2.22	33.88±1.22	63.22±2.16	49.28±2.33	47.65
I-4	4.17	60.46±0.43	32.10±1.71	44.76±0.35	43.69±0.41	39.11±2.22	57.31±1.42	51.48±1.40	39.77±0.54	45.65±0.52	36.10±0.57	45.04
I-5	5.09	57.57±1.19	43.62±2.67	60.49±0.93	44.64±1.03	41.41±0.63	61.85±1.23	48.02±0.87	42.48±0.41	84.41±2.03	57.84±3.18	54.23
I-6	4.64	63.82±0.87	48.85±0.45	57.23±0.88	44.40±2.05	47.72±0.21	62.76±1.04	55.74±0.69	46.72±0.41	58.42±1.04	21.61±0.29	50.73
I-7	5.05	65.79±2.81	50.16±0.78	57.69±0.35	48.91±0.21	45.05±1.31	76.61±2.39	55.86±0.87	49.08±1.41	68.36±1.04	26.22±3.21	54.37
I-8	3.49	18.75±3.79	17.19±1.18	21.45±0.81	25.56±0.54	20.18±0.42	39.03±1.48	37.76±3.99	33.40±2.84	47.12±2.06	75.46±0.29	33.59
I-9	3.09	3.18±2.74	0.31±0.78	2.80±0.70	12.40±0.54	8.90±0.56	37.78±0.39	33.15±1.60	33.52±1.22	44.18±2.07	34.29±0.49	21.05
I-10	3.76	21.82±2.19	23.99±1.77	31.24±0.88	32.08±0.71	23.70±1.52	42.55±0.39	45.37±1.20	35.29±1.06	39.44±1.41	78.26±0.99	37.37
I-11	4.92	60.20±0.87	54.87±2.08	59.91±1.41	50.57±0.62	37.41±0.36	55.95±0.79	46.52±1.06	53.32±0.61	86.78±3.11	41.04±0.57	54.66
I-12	4.61	64.80±1.51	67.03±0.39	53.15±1.95	53.77±0.36	43.84±0.21	75.25±0.52	51.48±0.20	77.84±0.82	88.25±0.85	82.54±1.03	65.8
I-13	2.80	15.90±1.55	7.12±0.23	0.00	12.87±0.36	8.18±0.21	31.77±0.20	21.39±2.22	15.37±0.41	58.87±3.20	29.02±1.24	20.05
I-14	3.91	26.75±4.06	25.95±0.23	21.45±0.53	31.96±0.21	21.88±1.83	56.18±0.39	30.61±3.73	21.97±0.74	18.42±0.39	51.91±0.57	30.71
I-15	3.91	19.19±2.33	17.32±2.61	18.88±1.05	21.76±0.62	19.46±0.42	31.77±1.29	25.54±3.81	15.49±0.61	55.14±1.09	38.24±1.71	26.28
I-16	3.91	3.29±2.37	8.69±0.82	16.90±1.58	20.46±0.21	15.21±7.31	35.51±1.42	16.55±2.69	12.78±1.14	38.64±1.55	46.64±0.99	21.47
I-17	4.29	52.96±3.47	44.40±0.82	50.70±1.26	39.90±0.62	36.44±1.11	48.23±1.77	48.48±2.42	27.39±0.74	52.09±2.18	28.19±3.02	42.88
I-18	4.64	54.82±1.52	49.63±2.16	53.73±0.73	44.64±1.03	35.10±0.42	49.25±0.59	42.95±1.38	46.49±1.08	66.10±1.89	27.54±1.51	47.03
I-19	5.34	68.75±0.33	65.72±1.59	59.91±1.07	40.61±1.23	61.67±0.76	68.44±1.94	59.77±0.53	48.14±1.47	73.79±2.74	24.74±2.00	57.15
I-20	4.64	41.34±1.55	24.65±0.78	39.42±1.15	28.99±0.21	25.16±1.38	48.00±1.71	31.77±2.22	29.40±0.20	47.29±0.24	23.09±2.00	33.91
I-21	5.63	65.24±1.33	72.53±1.04	45.34±1.41	46.42±0.21	31.59±1.67	70.59±0.20	42.25±0.35	32.11±2.55	88.93±0.39	43.02±0.57	53.8
I-22	3.07	48.03±3.01	0.00	24.94±1.01	33.14±1.23	12.54±2.00	56.18±0.39	34.65±1.04	18.79±2.13	0.00	74.80±1.31	30.31
I-23	4.28	66.01±1.00	11.43±0.45	87.18±0.73	52.11±0.54	28.68±1.89	79.11±2.58	52.51±1.00	84.21±0.82	49.04±3.43	53.15±2.45	56.34
I-24	3.55	40.24±2.64	1.88±0.78	34.73±2.27	40.02±0.21	16.06±0.76	61.06±0.52	55.62±0.53	8.06±0.71	6.67±0.85	71.34±1.48	33.57
Bifonazole	4.69	75.44±4.49	90.71±1.59	96.39±1.58	94.90±0.21	91.51±1.17	92.28±0.86	80.06±0.20	72.87±0.38	100.00	100.00	89.42

	Compd.	EC₅₀	Regression equation	R²	95% confidence interval
P. oryzae	I-08	49.17	y=－2.54＋1.48x	0.941	38.18~70.10
	I-10	33.34	y=－2.21＋1.44x	0.984	26.81~43.90
	I-12	15.67	y=－1.91＋1.59x	0.985	13.20~18.93
	I-22	46.03	y=－2.4＋1.45x	0.960	35.31~65.86
	I-24	20.77	y=－1.75＋1.33x	0.997	16.87~26.60
	Bifonazole	1.41	y=－0.21＋1.49x	0.947	0.72~2.12
B. cinerea	I-05	15.25	y=－1.97＋1.66x	0.992	12.94~18.24
	I-11	14.21	y=－1.4＋1.21x	0.985	11.41~17.92
	I-12	21.65	y=－2.09＋1.56x	0.970	18.15~26.57
	I-19	22.01	y=－1.82＋1.35x	0.992	17.92~28.13
	I-21	16.41	y=－1.85＋1.51x	0.982	13.72~20.02
	Bifonazole	1.78	y=－0.38＋1.41x	0.997	0.75~3.00
F. graminearum	I-07	22.84	y=－1.21＋0.89x	0.988	16.88~34.18
	I-12	17.3	y=－1.15＋0.93x	0.996	13.20~24.12
	I-21	19.71	y=－0.76＋0.59x	0.996	12.97~36.65
	I-23	12.76	y=－0.78＋0.71x	0.991	9.12~18.98
	Bifonazole	0.1	y=0.76＋0.77x	0.920	0.08~0.15
P. aphanidermatum	I-12	27.54	y=－2.68＋1.86x	0.976	23.41~33.34
	I-23	14.03	y=－2.73＋2.35x	0.963	9.87~20.48
	Bifonazole	14.87	y=－1.97＋1.66x	0.996	10.94~21.28
P. capsici	I-23	20.17	y=－3.95＋3.02x	0.997	18.07~22.62
P. capsici	Bifonazole	6.5	y=－2.59＋3.11x	0.985	5.83~7.23
S. sclerotiorum	I-21	16.53	y=－1.93＋1.57x	0.963	14.00~19.86
S. sclerotiorum	Bifonazole	11.94	y=－2.01＋1.89x	0.984	10.36~13.84

	Compd.	EC₅₀	Regression equation	R²	95% confidence interval
P. oryzae	I-08	49.17	y=－2.54＋1.48x	0.941	38.18~70.10
	I-10	33.34	y=－2.21＋1.44x	0.984	26.81~43.90
	I-12	15.67	y=－1.91＋1.59x	0.985	13.20~18.93
	I-22	46.03	y=－2.4＋1.45x	0.960	35.31~65.86
	I-24	20.77	y=－1.75＋1.33x	0.997	16.87~26.60
	Bifonazole	1.41	y=－0.21＋1.49x	0.947	0.72~2.12
B. cinerea	I-05	15.25	y=－1.97＋1.66x	0.992	12.94~18.24
	I-11	14.21	y=－1.4＋1.21x	0.985	11.41~17.92
	I-12	21.65	y=－2.09＋1.56x	0.970	18.15~26.57
	I-19	22.01	y=－1.82＋1.35x	0.992	17.92~28.13
	I-21	16.41	y=－1.85＋1.51x	0.982	13.72~20.02
	Bifonazole	1.78	y=－0.38＋1.41x	0.997	0.75~3.00
F. graminearum	I-07	22.84	y=－1.21＋0.89x	0.988	16.88~34.18
	I-12	17.3	y=－1.15＋0.93x	0.996	13.20~24.12
	I-21	19.71	y=－0.76＋0.59x	0.996	12.97~36.65
	I-23	12.76	y=－0.78＋0.71x	0.991	9.12~18.98
	Bifonazole	0.1	y=0.76＋0.77x	0.920	0.08~0.15
P. aphanidermatum	I-12	27.54	y=－2.68＋1.86x	0.976	23.41~33.34
	I-23	14.03	y=－2.73＋2.35x	0.963	9.87~20.48
	Bifonazole	14.87	y=－1.97＋1.66x	0.996	10.94~21.28
P. capsici	I-23	20.17	y=－3.95＋3.02x	0.997	18.07~22.62
P. capsici	Bifonazole	6.5	y=－2.59＋3.11x	0.985	5.83~7.23
S. sclerotiorum	I-21	16.53	y=－1.93＋1.57x	0.963	14.00~19.86
S. sclerotiorum	Bifonazole	11.94	y=－2.01＋1.89x	0.984	10.36~13.84

含吡啶环的1-唑基-1,1-二芳基甲烷类化合物的合成及杀菌活性研究