58905-19-4Relevant articles and documents
Synthesis of the Methanesulfonates of α-(4-Chlorophenyl)-α-[1-(2-chlorophenyl)ethenyl]-1H-1,2,4-triazole- 1-ethanol and α-[1-(2-Chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)- 1H-1,2,4-triazole-1-ethanol, Aloha Styryl Carbinol Antifungal Agents
Pesti, Jaan A.,Downard, Jill A.,Lauritsen, Mark D.,Kauffman, Goss S.,Bryant III, Walter M.,Huhn, George F.,Arnett, John F.,Yule, Robert E.,Segretario, James,Nelson, Kimberly A.,Gorko, Edward F.,Page, Gary O.,Lloyd, Lisa M.,Olson, Richard E.,Barnum, Christopher S.,Mrowca, Joseph J.
, p. 249 - 255 (1998)
The methanesulfonates of (α-(4-chlorophenyl)-α-[1-(2-chlorophenyl)ethenyl]-1H-1,2,4-triazole- l-ethanoI and α-[1-(2-chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)-1H-1,2,4- triazole-1-ethanol (1a,b) are orally effective α-styryl carbinol derivatives develop
Synthesis, optimization, antifungal activity, selectivity, and cyp51 binding of new 2-aryl-3-azolyl-1-indolyl-propan-2-ols
Lebouvier, Nicolas,Pagniez, Fabrice,Na, Young Min,Shi, Da,Pinson, Patricia,Marchivie, Mathieu,Guillon, Jean,Hakki, Tarek,Bernhardt, Rita,Yee, Sook Wah,Simons, Claire,Lézé, Marie-Pierre,Hartmann, Rolf W.,Mularoni, Angélique,Le Baut, Guillaume,Krimm, Isabelle,Abagyan, Ruben,Pape, Patrice Le,Borgne, Marc Le
, p. 1 - 32 (2020/08/17)
A series of 2-aryl-3-azolyl-1-indolyl-propan-2-ols was designed as new analogs of fluconazole (FLC) by replacing one of its two triazole moieties by an indole scaffold. Two different chemical approaches were then developed. The first one, in seven steps, involved the synthesis of the key intermediate 1-(1H-benzotriazol-1-yl)methyl-1H-indole and the final opening of oxiranes by imidazole or 1H-1,2,4-triazole. The second route allowed access to the target compounds in only three steps, this time with the ring opening by indole and analogs. Twenty azole derivatives were tested against Candida albicans and other Candida species. The enantiomers of the best anti-Candida compound, 2-(2,4-dichlorophenyl)-3-(1H-indol-1-yl)-1-(1H-1,2,4-triazol-1-yl)-propan-2-ol (8g), were analyzed by X-ray diffraction to determine their absolute configuration. The (?)-8g enantiomer (Minimum inhibitory concentration (MIC) = IC80 = 0.000256 μg/mL on C. albicans CA98001) was found with the S-absolute configuration. In contrast the (+)-8g enantiomer was found with the R-absolute configuration (MIC = 0.023 μg/mL on C. albicans CA98001). By comparison, the MIC value for FLC was determined as 0.020 μg/mL for the same clinical isolate. Additionally, molecular docking calculations and molecular dynamics simulations were carried out using a crystal structure of Candida albicans lanosterol 14α-demethylase (CaCYP51). The (?)-(S)-8g enantiomer aligned with the positioning of posaconazole within both the heme and access channel binding sites, which was consistent with its biological results. All target compounds have been also studied against human fetal lung fibroblast (MRC-5) cells. Finally, the selectivity of four compounds on a panel of human P450-dependent enzymes (CYP19, CYP17, CYP26A1, CYP11B1, and CYP11B2) was investigated.
Triazole derivative as well as preparation method and application thereof
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Paragraph 0081; 0085-0087, (2020/06/09)
The invention relates to a triazole derivative as well as a preparation method and application thereof, which belong to the technical field of organic synthetic drugs. The structure of the triazole derivative is shown as a formula I. In the formula I, R1 and R2 are H, Cl, Br,-CF3,-CH(CH3)2 or -OCH3, and R1 and R2 are not H at the same time. R3 is -CH2 or -COCH2; X and Y are N or C, X and Y are not C at the same time, and X and Y are not N at the same time. The triazole derivative disclosed by the invention has a certain inhibition effect on germs of various crop diseases. Small toxic andside effects on plants are achieved. The preparation method of the triazole derivative is simple.
In order to 1 - (4 - chlorophenyl) -2 - (1 H - 1, 2, 4 - triazole -1 - yl) ethanone synthetic triabimefron method
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Paragraph 0032; 0033; 0034; 0039, (2019/04/10)
The invention relates to the field of organic synthesis, in particular to a using the intermediate 1 - (4 - chlorophenyl) - 2 - (1 H - 1, 2, 4 - triazole - 1 - yl) ethanone synthetic triabimefron method, comprises the following steps: (1) 2, 4' - dichloro ethanone with 1, 2, 4 - triazole or 1, 2, 4 - three nitrogen zuozuo salt undergo nucleophilic substitution reaction to obtain 1 - (4 - chlorophenyl) - 2 - (1 H - 1, 2, 4 - triazole - 1 - yl) ethyl ketone; (2) 1 - (4 - chlorophenyl) - 2 - (1 H - 1, 2, 4 - triazole - 1 - yl) ethanone with 1 - cyclopropyl halogenated ethane Grignard reagent, 1 - cyclopropyl halogenated ethane organic zinc reagent or a mixture thereof a nucleophilic addition reaction triabimefron. The present invention provides a method of synthesis of triabimefron short route, mild reaction, high yield, the reaction process does not use a foul smell of sulfur ylide reagent, does not need to use dangerous [...], also will not produce a large amount of phosphorus-containing waste water, suitable for large-scale industrial production.
Method for preparing cyproconazole with 2,4'-dichloroacetophenone being raw material
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Page/Page column 7-10, (2019/04/26)
The invention relates to the field of organic synthesis and especially relates to a method for preparing cyproconazole with 2,4'-dichloroacetophenone being a raw material. The method includes: a) performing a nucleophilic substitution reaction on the 2,4'-dichloroacetophenone and 1,2,4-triazole or 1,2,4-triazole salt to obtain 1-(4-chlorophenyl)-2-(1H-1,2,4-triazole-1-yl)ethyl ketone; b) performing a nucleophilic addition reaction on the 1-(4-chlorophenyl)-2-(1H-1,2,4-triazole-1-yl)ethyl ketone with one or more of a 3-halogenated-1-butylene Grignard reagent, a 3-halogenated-1-butylene organozinc reagent, a 1-halogenated-2-butylene Grignard reagent and a 1-halogenated-2-butylene organozinc reagent, thus generating 2-(4-chlorophenyl)-3-methyl-1-(1H-1,2,4-triazole-1-yl)-4-pentene-2-ol; c) performing a ring forming reaction on the 2-(4-chlorophenyl)-3-methyl-1-(1H-1,2,4-triazole-1-yl)-4-pentene-2-ol with one or more Simmons-Smith reagents prepared from dihalogenated methane, thus preparing the cyproconazole. The preparation method is short in route, gentle in reaction and high in yield. The reactions are free of dangerous reagents, so that the method is suitable for large scale industrial production.
Antifungal Compounds
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Paragraph 0073; 0074, (2018/07/30)
Compounds and compositions having antifungal activity, and methods of using the antifungal compounds and compositions, are described for use in treating fungal infections.
Novel carbazole-triazole conjugates as DNA-targeting membrane active potentiators against clinical isolated fungi
Zhang, Yuan,Tangadanchu, Vijai Kumar Reddy,Bheemanaboina, Rammohan R. Yadav,Cheng, Yu,Zhou, Cheng-He
, p. 579 - 589 (2018/06/20)
A series of carbazole-triazole conjugates were designed, synthesized and characterized by IR, NMR, and HRMS spectra. Biological assay showed that most of the synthesized compounds exhibited moderate and even strong antifungal activities, especially 3,6-dibromocarbazolyl triazole 5d displayed excellent inhibitory efficacy against most of the tested fungal strains (MIC = 2–32 μg/mL) and effectively fungicidal ability towards C. albicans, C. tropicals and C. parapsilosis ATCC 22019 (MFC = 4–8 μg/mL). Its combination use with fluconazole could enhance the antifungal efficacy, and compound 5d also did not obviously trigger the development of resistance in C. albicans even after 10 passages. Preliminary mechanism study revealed that the active molecule 5d could depolarize fungal membrane potential and intercalate into DNA to possibly block DNA replication, thus possibly exhibiting its powerful antifungal abilities. Conjugate 5d could interact with HSA, which was constructive for the further design, modification and screening of drug molecules. Docking investigation demonstrated a non-covalent binding of 5d with CYP51 through hydrogen bond and hydrophobicity. These results strongly suggested that compound 5d could act as a potential template for the development of promising antifungal drugs.
Design, synthesis, & biological activity of new triazole & nitro-triazole derivatives as antifungal agents
Sadeghpour, Hossein,Khabnadideh, Soghra,Zomorodian, Kamiar,Pakshir, Keyvan,Hoseinpour, Khadijeh,Javid, Nabiollah,Faghih-Mirzaei, Ehsan,Rezaei, Zahra
, (2017/08/26)
In this study two series of fluconazole derivatives bearing nitrotriazole (series A) or piperazine ethanol (series B) side chain were designed and synthesized and then docked in the active site of lanosterol 14α-demethylase enzyme (1EA1) using the Autodock 4.2 program (The scripps research institute, La Jolla, CA, USA). The structures of synthesized compound were confirmed by various methods including elemental and spectral (NMR, CHN, and Mass) analyses. Then antifungal activities of the synthesized compound were tested against several natural and clinical strains of fungi using a broth microdilution assay against several standard and clinical fungi. Nitrotriazole derivatives showed excellent and desirable antifungal activity against most of the tested fungi. Among the synthesized compounds, 5a-d and 5g, possessing nitrotriazole moiety, showed maximum antifungal activity, in particular against several fluconazole-resistant fungi.
Novel alkylated azoles as potent antifungals
Shrestha, Sanjib K.,Garzan, Atefeh,Garneau-Tsodikova, Sylvie
supporting information, p. 309 - 318 (2017/04/11)
Fluconazole (FLC) is the drug of choice when it comes to treat fungal infections such as invasive candidiasis in humans. However, the widespread use of FLC has resulted in the development of resistance to this drug in various fungal strains and, simultaneously has occasioned the need for new antifungal agents. Herein, we report the synthesis of 27 new FLC derivatives along with their antifungal activity against a panel of 13 clinically relevant fungal strains. We also explore their toxicity against mammalian cells, their hemolytic activity, as well as their mechanism of action. Overall, many of our FLC derivatives exhibited broad-spectrum antifungal activity and all compounds displayed an MIC value of 0.03?μg/mL against at least one of the fungal strains tested. We also found them to be less hemolytic and less cytotoxic to mammalian cells than the FDA approved antifungal agent amphotericin B. Finally, we demonstrated with our best derivative that the mechanism of action of our compounds is the inhibition of the sterol 14α-demethylase enzyme involved in ergosterol biosynthesis.
Synthesis and Antimicrobial Activity of Novel 2-Substituted Phenoxy-N-(4-substituted Phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-yl)acetamide Derivatives
Liao, Guo-Ping,Zhou, Xia,Xiao, Wei,Xie, Yan,Jin, Lin-Hong
, p. 1506 - 1513 (2017/03/27)
A series of 2-substituted phenoxy-N-(4-substituted phenyl-5-(1H-1,2,4-triazol-1-yl)thiazole-2-yl)acetamide derivatives 8a, 8b, 8c, 8d, 8e, 8f, 8g, 8h, 8i, 8j, 8k, 8l, 8m, 8n, 8o, 8p, 8q, 8r, 8s, 8t was synthesized by the reaction of phenoxyacetyl chloride 7 with intermediate 4-substituted phenyl-5-(1H-1,2,4-triazol-1-yl)thiazol-2-amine 5. Their structures were confirmed by 1H NMR, 13C NMR, MS, IR, and elemental analyses. The synthesized compounds were also screened for their antimicrobial activity against three types of plant fungi (Gibberella zeae, Phytophthora infestans, and Paralepetopsis sasakii) and two kinds of bacteria [Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac)] showing promising results. In particular, 8b, 8f, 8g, and 8h exhibited excellent antibacterial activity against Xoo, with 50% effective concentration (EC50) values of 35.2, 80.1, 62.5, and 82.1 μg/mL, respectively, which are superior to the commercial antibacterial agent bismerthiazol (89.9 μg/mL). The preliminary structure–activity relationship studies of these compounds are also briefly described.
