Synthesis, Crystal Structure, Antifungal Activity, and Docking Study of Difluoromethyl Pyrazole Derivatives

Abstract

Nine novel difluoromethylpyrazole acyl urea derivatives were synthesized via seven steps conveniently. All the structures were determined by 1H‐NMR, 13C‐NMR, HRMS, and X‐ray diffraction. The in vivo fungicidal activities were determined against Corynespora mazei, Botrytis cinerea, Fusarium oxysporum, and Pseudomonas syringae, respectively. The bioassay results indicated that some of them displayed good control effective (around 50 and 80%) against P. syringae and B. cinerea at 50 mg/L, respectively, which is better than control. It is possible that difluoromethylpyrazole acyl urea derivatives can be a leading compound for the development of new fungicides against the two fungi with further structure optimization. Furthermore, docking model was studied to establish structure–activity relationship of difluoromethylpyrazole acyl urea derivatives.

Synthesis and Fungicidal Activity of Hydrated Geranylated Phenols against Botrytis cinerea

“…Recently, it has been shown that the antifungal activity of a variety of compounds is mainly due to inhibition of succinate dehydrogenase (SDH) which is a component of the mitochondrial respiratory chain and the tricarboxylic acid cycle [21][22][23]. Thus, the interactions of antifungal compounds with the ubiquinone binding site have been evaluated to understand the experimental activity shown by different series of related compounds [24][25][26][27][28]. In this work, we have performed molecular docking studies of geranylated phenols carrying one (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33), two (34)(35)(36)(37)(38) or no (14, 18, 19) hydroxyl groups in the side alkyl chain.…”

“…Thus, the interactions of antifungal compounds with the ubiquinone binding site have been evaluated to understand the experimental activity shown by different series of related compounds [24][25][26][27][28]. In this work, we have performed molecular docking studies of geranylated phenols carrying one (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33), two (34)(35)(36)(37)(38) or no (14, 18, 19) hydroxyl groups in the side alkyl chain. Molecular coupling of these compounds to a single crystal structure of SDH (PDB code 2FBW) was carried out by using Glide software.…”

“…13 C NMR (100 MHz, (CDCl 3 ) (Figure S3, Supplementary Material): δ 155.4 (C-1), 155.4 (C-3), 137.8 (C-3 ), 130.6 (C-5), 122.5 (C-2 ), 119.1 (C-4), 107.5 (C-6), 103.3 (C-2), 71.4 (C-7 ), 43.2 (C-6 ), 39.9 (C-4 ), 29.2 (C-8 y CH 3 -C7 ), 29.1 (C-1 ), 22.4 (C-5 ), 16.1 (CH 3 -C3 ). EIMS m/z (%): 264 [M] + (3), 123 (100), 161 (25), 163 (15), 175 (18), 177 (12), 246 (15); HREIMS [M] + found 264.1724, calcd for C 16 H 24 O 3 264.1725 (Figure S20, Supplementary Material).…”

“…Binding energies, obtained from molecular docking studies and antifungal activities against B. cinerea (EC 50 values) of geranylated phenols with one(14,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33), two(34)(35)(36)(37)(38) or none(18,19,21) hydroxyl groups in the side alkyl chain. CBE is used for comparison 1 .…”

Synthesis and herbicidal activity of novel pyrazole aromatic ketone analogs as HPPD inhibitor

“…Many studies 6,21,22 on HPPD inhibitors have proven that prodrug-type HPPD herbicides are an effective method of obtaining new HPPD inhibitors, such as the commercial HPPD herbicides benzobicyclon, isoxaflutole, benzofenap, pyrazolynate and pyrazoxyfen. As a part of our job in designing and synthesizing novel pyrazole derivatives with pesticidal activity, [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] the pyrazole HPPD herbicides were used as lead compound, the 3-position of benzene ring was replaced by a flexible chain, and the hydroxyl group of pyrazole ring was also etherified or esterified. Through the prodrug strategy, we hoped that better herbicidal activity would result.…”