123632-22-4

Upstream product

• 1030268-24-6 trimethylsulphoxonium iodide 
• 86404-63-9 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone 
• 70775-39-2 dimethylsulfoxonium methylide 
• 1774-47-6 trimethylsulfoxonium iodide 
• 118689-07-9 (S)-(+)-2(2,4-Difluorophenyl)-3-(1,2,4-triazol-1-yl)-1,2-propanediol 
• 57-09-0 cetyltrimethylammonim bromide 
• 2181-42-2 trimethylsulphonium iodide 
• 372-18-9 1,3-Difluorobenzene 
• 51336-94-8 2-chloro-1-(2,4-dichlorophenyl)ethanone 

Downstream Products

• 205435-16-1 1-[2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl]-1-ethyl-1-methylhydrazinium inner salt 

Relevant academic research and scientific papers

Novel potentially antifungal hybrids of 5-flucytosine and fluconazole: Design, synthesis and bioactive evaluation

A series of novel potentially antifungal hybrids of 5-flucytosine and fluconazole were designed, synthesized and characterized by 1H NMR, 13C NMR, IR and HRMS spectra. Bioactive assay manifested that some prepared compounds showed moderate to good antifungal activities in comparison with fluconazole and 5-flucytosine. Remarkably, the 3,4-dichlorobenzyl hybrid 7h could inhibit the growth of C. albicans ATCC 90023 and clinical resistant strain C. albicans with MIC values of 0.008 and 0.02 mM, respectively. The active molecule 7h could not only rapidly kill C. albicans but also efficiently permeate membrane of C. albicans. Molecular docking study revealed that compound 7h could interact with the active site of CACYP51 through hydrogen bond. Quantum chemical studies were also performed to explain the high antifungal activity. Further preliminary mechanism research suggested that molecule 7h could intercalate into calf thymus DNA to form a steady supramolecular complex, which might block DNA replication to exert the powerful bioactivities.

Synthesis of some new propanol derivatives analogous to fluconazole

A series of 2-(2,4-difluorophenyl)-1-(1H-1,2,4 triazol-1-yl-methyl)-3- (substituted heterocycl)-propan-2-ol, which are analogous to fluconazole, were synthesized via the reaction of 2-(2,4-difluorophenyl)-2-[1-(1,2,4- triazolmethide)]oxiran with various heterocyclic systems.

Synthesis and crystallographic characterization of 1-((2-(2,4- Difluorophenyl)oxiran-2-yl)methyl)-1H-1,2,4-triazole: A crucial intermediate for the synthesis of azole antifungal drugs

Preparation of oxirane 3 was accomplished in two steps. 1H-1,2,4-triazole was reacted with 2,4-difluoro-α-chloroacetophenone 1 in presence of K 2CO3 in refluxing toluene to provide compound 2. Compound 2 was treated with trimethylsul

Novel fluconazole derivatives with promising antifungal activity

The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activity of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against mammalian cells. The best compounds from our study exhibited broad-spectrum activity against most of the fungal strains tested, with excellent MIC values against a number of clinical isolates. The most promising compounds were found to be less hemolytic than the least hemolytic FDA-approved azole antifungal agent voriconazole (VOR). Finally, we demonstrated that the synthetic alkyl-amino FLC analogues displayed chain-dependent fungal membrane disruption as well as inhibition of ergosterol biosynthesis as possible mechanisms of action.

Azole-triphenylphosphonium conjugates combat antifungal resistance and alleviate the development of drug-resistance

Azole antifungals are commonly used to treat fungal infections but have resulted in the occurrence of drug resistance. Therefore, developing azole derivatives (AZDs) that can both combat established drug-resistant fungal strains and evade drug resistance is of great importance. In this study, we synthesized a series of AZDs with a fluconazole (FLC) skeleton conjugated with a mitochondria-targeting triphenylphosphonium cation (TPP+). These AZDs displayed potent activity against both azole-sensitive and azole-resistant Candida strains without eliciting obvious resistance. Moreover, two representative AZDs, 20 and 25, exerted synergistic antifungal activity with Hsp90 inhibitors against C. albicans strains resistant to the combination treatment of FLC and Hsp90 inhibitors. AZD 25, which had minimal cytotoxicity, was effective in preventing C. albicans biofilm formation. Mechanistic investigation revealed that AZD 25 inhibited the biosynthesis of the fungal membrane component ergosterol and interfered with mitochondrial function. Our findings provide an alternative approach to address fungal resistance problems.

Voriconazole synthesis process

The invention discloses a synthesis process of voriconazole bulk drug, which comprises the following steps: preparing halogenated ethyl fluorouracil and carrying out Grignard reaction. 2 - (2, 4 - Difluorophenyl) -3 - (1, 2, 4 - triazol -1 -yl) -1, 2 - propylene glycol was oxidized to give a propylene oxide compound. The Grignard reagent and the propylene oxide compound are mixed and reacted to obtain voriconazole. To the synthesis process, the reaction steps can be simplified, the dehydrochlorination and hydrogenolysis of palladium carbon are not needed, the reaction period is shortened, and furthermore, the energy consumption is reduced, the cost is reduced, and voriconazole and the racemate thereof are obtained with higher yield.

TRIAZOLE DERIVATIVES WITH ANTIFUNGAL ACTIVITY

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, Q2, L1 and n are as defined herein. The compounds have antifungal properties and are useful in the treatment of fungal infections, including infections that are resistant to conventions anti-fungal agents. Q1 is selected from: (Formulae Ia, Ib, Ic, Id, Ie, If, Ig, Ih, Ii, Ij and Ik) wherein * indicates the point of attachment to L1.

Antibacterial drug and preparation method thereof

The invention discloses an antibacterial drug. The antibacterial drug is 2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3-(1H-1,2,3,4-tetrazol-1-yl)-2-propanol, the compound is obtained by modifyingfluconazole and introducing a tetrazole ring. Compared with fluconazole, the compound has wider antimicrobial activity spectrum. The invention also discloses a preparation method of the antibacterialdrug. The method comprises the step of introducing the tetrazole ring to obtain 2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3-(1H-1,2,3,4-tetrazol-1-yl)-2-propanol on the basis of retaining moststructures with drug effects on fluconazole.

Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans

Abstract: Azole antifungals are an important class of antifungal drugs due to their low cost, ability to be administered orally, and broad-spectrum activity. However, their widespread and long-term use have given rise to adaptation mechanisms that render these compounds less effective against common fungal pathogens, including Candida albicans. New antifungals are desperately needed as drug-resistant strains become more prevalent. We recently showed that copper supplementation potentiates the activity of the azole antifungal fluconazole against the opportunistic fungal pathogen C. albicans. Here, we report eight new azole analogues derived from fluconazole in which one triazole group has been replaced with a metal-binding group, a strategy designed to enhance potentiation of azole antifungal activity by copper. The bioactivity of all eight compounds was tested and compared to that of fluconazole. Three of the analogues showed activity against C. albicans and two had lower levels of trailing growth. One compound, Flu-TSCZ, was found to impact the levels, speciation, and bioavailability of cellular metals. Graphic abstract: [Figure not available: see fulltext.]

Synthesis, optimization, antifungal activity, selectivity, and cyp51 binding of new 2-aryl-3-azolyl-1-indolyl-propan-2-ols

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.