Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid Amides

Abstract

A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

2-(Azolyl)anilines: methods of synthesis, cyclocondensations, and biological properties

“…Besides, structure-activity relationship was discussed in this paper. 21 Testing the inhibitory properties of [2-(1-aryl-1H-1,2,4-triazol-3-yl)phenyl](heterylmethyl)amines 70 toward VEGF-1 and VEGF-2 receptors showed that compound with 3-fluoro(bromo, tert-butyl)phenyl substituents and 4-pyridyl fragment had IC 50 of 0.046-0.13 μM. 32 The molecular docking studies with VEGF receptor inhibitor vatalanib as reference have shown that lead compounds were the promising anticancer drugs.…”

“…Exhaustive research of antifungal activity using molecular docking was conducted by Du, 21 and it was found that 1-methyl-N-[2-(1H-heteryl)phenyl]-3-(difluoromethyl)-1H-pyrazole-4-carboxamides 53 inhibited the growth of Сolletotrichum orbiculare, Rhizoctonia solani, Phytophthora infestans, Pythium aphanidermatum, Fusarium moniliforme, Botryosphaeria berengeriana, and Botrytis cinerea up to 17-94%. Molecules bearing the 1-indazole and 5-bromo-1-indazole fragments were the most effective (IC 50 5.5-96 μg/ml) exceeding the reference fungicide boscalid (2-chloro-N-(4'-сhlorobіphenyl-2-yl)-nicotinamide).…”

“…[22][23][24]40,61 A detailed study dedicated to the search of α 1 -adrenergic receptor agonists among derivatives of 2-(1H-pyrazol-5-yl)-aniline (21) and 2-(1H-1,2,4-triazol-3-yl)aniline (21) was done by Speake. 3 As a result, it was found that these compounds showed high selectivity toward α 1В -and α 1D -receptors.…”

Synthesis and Nematocidal Activity of N‐Substituted 3‐Methyl‐1H‐pyrazole‐4‐carboxamide Derivatives Against Meloidogyne incognita

“…In recent years, heterocyclic compounds play an important role in organic chemistry , medicinal chemistry , pesticidal chemistry , and inorganic chemistry . Among them, five membering pyrazole compounds had been considerably used in synthetic medicines and pesticides , as they possessed diversity biological activities, such as herbicidal , anti‐tobacco mosaic virus , insecticidal , antimicrobial , antioxidant , antifungal , xanthine oxidase inhibitory , and anti‐inflammatory activity . Some pyrazole compounds have been developed as commercial drugs and pesticides, such as tebufenpyral, fipronil, fenpyroximate, tolfenpyrad, and chlorantraniliprole.…”

Synthesis, Antifungal Activity and QSAR of Novel Pyrazole Amides as Succinate Dehydrogenase Inhibitors

“…2 Bioassays have shown that some target molecules exhibited good antifungal activities against Rhizoctonia solani, Botrytis cinerea and Pythium aphanidermatum. By comparing the structure and activity, we found that amides with indazole groups have high antibacterial activity.…”