127000-91-3

Usage

Uses

Used in Pharmaceutical Industry:
(2R,3R)-3-Amino-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol is used as an antifungal agent for treating vaginal yeast infections. It works by inhibiting the growth of fungi by disrupting the synthesis of ergosterol, an essential component of fungal cell membranes.
Used in Topical Administration:
(2R,3R)-3-Amino-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol is used in various pharmaceutical formulations for topical administration, such as creams, suppositories, and vaginal tablets. This allows for targeted treatment of fungal infections in the vaginal area, minimizing systemic side effects and enhancing patient compliance.

Upstream product

• 126945-34-4 Methanesulfonic acid (1S,2S)-2-(2,4-difluoro-phenyl)-2-hydroxy-1-methyl-3-[1,2,4]triazol-1-yl-propyl ester 
• 124627-86-7 1-(((2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiran-2-yl)-methyl)-1H-1,2,4-triazole 
• 274682-91-6 1-(2,4-difluorophenyl)-2-propanone 
• 367-25-9 2,4-difluorophenylamine 
• 135133-23-2 (3R)-2-(2,4-difluorophenyl)-3-(tetrahydropyran-2-yloxy)-1-[1,2,4]triazol-1-yl-butan-2-ol 
• 135267-12-8 2-((R)-1-((R)-2-(2,4-difluorophenyl)oxiran-2-yl)ethoxy)tetrahydro-2H-pyran 
• 127001-03-0 (2R)-2',4'-Difluoro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone 
• 132507-89-2 (2R,3R)-2-(2,4-Difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol 
• 348-57-2 2,4-difluorobromobenzene 
• 102429-07-2 2-bromo-2',4'-difluoroacetophenone 
• 86404-63-9 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazolyl)ethanone 
• 169058-26-8 (4R,5R)-4-(2,4-Difluorophenyl)-5-methyl-4-<(1H-1,2,4-triazol-1-yl)methyl>-2-oxazolidinone 

Downstream Products

• 126917-83-7 (2R*,3R*)-3-(4-Chlorophthalimido)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol 
• 126916-58-3 4-Chloro-N-[(1S,2S)-2-(2,4-difluoro-phenyl)-2-hydroxy-1-methyl-3-[1,2,4]triazol-1-yl-propyl]-benzamide 
• 126916-61-8 4-Acetylamino-N-[(1S,2S)-2-(2,4-difluoro-phenyl)-2-hydroxy-1-methyl-3-[1,2,4]triazol-1-yl-propyl]-benzamide 
• 126917-19-9 (E)-1-[(4S,5S)-5-(2,4-Difluoro-phenyl)-4-methyl-5-[1,2,4]triazol-1-ylmethyl-oxazolidin-3-yl]-3-(4-trifluoromethyl-phenyl)-propenone 
• 132507-72-3 (4R^*,5R^*)-5-(2,4-Difluorophenyl)-4-methyl-3-(5-methyl-4-hexenoyl)-5-<(1H-1,2,4-triazol-1-yl)methyl>oxazolidine 
• 126916-84-5 (4-Chloro-phenyl)-[(4R,5R)-5-(2,4-difluoro-phenyl)-4-methyl-5-[1,2,4]triazol-1-ylmethyl-oxazolidin-3-yl]-methanone 
• 126917-17-7 (E)-3-(4-Chloro-phenyl)-1-[(4S,5S)-5-(2,4-difluoro-phenyl)-4-methyl-5-[1,2,4]triazol-1-ylmethyl-oxazolidin-3-yl]-propenone 
• 126916-89-0 [(4R,5R)-5-(2,4-Difluoro-phenyl)-4-methyl-5-[1,2,4]triazol-1-ylmethyl-oxazolidin-3-yl]-(4-trifluoromethyl-phenyl)-methanone 
• 126945-36-6 [(4S,5S)-5-(2,4-Difluoro-phenyl)-4-methyl-5-[1,2,4]triazol-1-ylmethyl-oxazolidin-3-yl]-(2-fluoro-4-trifluoromethyl-phenyl)-methanone 
• 126916-86-7 [(4S,5S)-5-(2,4-Difluoro-phenyl)-4-methyl-5-[1,2,4]triazol-1-ylmethyl-oxazolidin-3-yl]-pentafluorophenyl-methanone 
• 126916-89-0 [(4S,5R)-5-(2,4-Difluoro-phenyl)-4-methyl-5-[1,2,4]triazol-1-ylmethyl-oxazolidin-3-yl]-(4-trifluoromethyl-phenyl)-methanone 
• 1026929-28-1 2-Amino-N-[(1R,2R)-2-(2,4-difluoro-phenyl)-2-hydroxy-1-methyl-3-[1,2,4]triazol-1-yl-propyl]-4-fluoro-benzamide 
• 1027905-92-5 2-Amino-N-[(1R,2R)-2-(2,4-difluoro-phenyl)-2-hydroxy-1-methyl-3-[1,2,4]triazol-1-yl-propyl]-4,5-difluoro-benzamide 
• 206350-07-4 2-Amino-4-chloro-N-[(1R,2R)-2-(2,4-difluoro-phenyl)-2-hydroxy-1-methyl-3-[1,2,4]triazol-1-yl-propyl]-benzamide 

Relevant academic research and scientific papers

Asymmetric Catalytic Epoxidation of Terminal Enones for the Synthesis of Triazole Antifungal Agents

An enantioselective epoxidation of α-substituted vinyl ketones was realized to construct the key epoxide intermediates for the synthesis of various triazole antifungal agents. The reaction proceeded efficiently in high yields with good enantioselectivities by employing a chiral N,N′-dioxide/ScIII complex as the chiral catalyst and 35% aq. H2O2 as the oxidant. It enabled the facile transformation for optically active isavuconazole, efinaconazole, and other potential antifungal agents.

Design, synthesis, and structure-activity relationship studies of novel triazole agents with strong antifungal activity against Aspergillus fumigatus

The incidence of invasive fungal infections has dramatically increased for several decades. In order to discover novel antifungal agents with broad spectrum and anti-Aspergillus efficacy, a series of novel triazole derivatives containing 1,2,3-benzotriazin-4-one was designed and synthesized. Most of the compounds exhibited stronger in vitro antifungal activities against tested fungi than fluconazole. Moreover, 6m showed comparable antifungal activity against seven pathogenic strains as voriconazole and albaconazole, especially against Aspergillus fumigatus (MIC = 0.25 μg/ml), and displayed moderate antifungal activity against fluconazole-resistant strains of Candida albicans. A clear SAR study indicated that compounds with groups at the 7-position resulted in novel antifungal triazoles with more effectiveness and a broader-spectrum.

Triazole alcohol derivative, and preparation method and application thereof

The invention relates to a triazole alcohol derivative, and a preparation method and an application thereof. The chemical structure of the triazole alcohol derivative is represented by formula I, A inthe formula I represents a benzene ring or a substituted benzene ring, and the substituent group of the substituted benzene ring can be located at each position of the benzene ring, is monosubstituted or polysubstituted, and is selected from: a) halogen which is F, Cl, Br or I; b) an electron-withdrawing group, wherein the electron withdrawing group is a cyano group, a nitro group or a trifluoromethyl group; c) a C1-4 low alkyl group or a halogen-substituted low alkyl group; and d) a C1-4 low alkoxy group or a halogen-substituted low alkoxy group. The compound has the advantages of high antifungal activity, low toxicity, wide antibacterial spectrum and the like, and can be used for preparing antifungal medicines.

Anti-Selective Catalytic Asymmetric Nitroaldol Reaction of α-Keto Esters: Intriguing Solvent Effect, Flow Reaction, and Synthesis of Active Pharmaceutical Ingredients

A rare-earth metal/alkali metal bimetallic catalyst proved particularly effective for enantioselectively coupling nitroalkanes and α-keto esters in an anti-selective manner to afford synthetically versatile, densely functionalized, and optically active α-nitro tertiary alcohols. A chiral diamide ligand captured two distinct metal cations, giving rise to a catalytically competent solid-phase heterobimetallic catalyst by simple mixing via self-assembly. The advantage of the solid-phase asymmetric catalyst was realized by successful application to the enantio- and diastereoselective reaction in a continuous-flow platform. The use of closely related solvents in terms of structures and polarity parameters, THF and its methylated congener 2-Me-THF, had an unexpectedly large solvent effect both on the reaction rate and the stereoselectivity. The nitroaldol products share a privileged unit for active pharmaceutical ingredients, as demonstrated by the streamlined enantioselective synthesis of the marketed antifungal agents efinaconazole and albaconazole.

Improved laboratory synthesis of YC-071, a potent azole antifungal agent

An improved laboratory synthesis of YC-071, a potent azole antifungal agent, has been developed. Compared with the original route, the new route is operationally simple, requiring only limited purification of all the intermediates. The new route is an imp

Method for preparing philippines Kang Zuo

The invention discloses a preparation method of efinaconazole (I). The preparation method comprises the following steps: performing asymmetric addition reaction on 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazole-1-yl)aceton (II) and nitroethane in the presence of a catalyst cupreine and a promoter benzoic acid to generate (2R,3R)-3-nitro-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazole-1-yl)-2-butanol (III); performing nitro reduction reaction on the intermediate (III) to generate (2R,3R)-3-amino-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazole-1-yl)-2-butanol (IV); and performing cyclization reaction on the intermediate (IV) and 1,5-di-halogen-3-methylene pentane (V) to prepare efinaconazole (I). The preparation method is easily available in raw materials and concise in process, is economical and environment-friendly and is suitable for industrial production.

Design, synthesis, and structure-activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates

In order to further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (I), two series of novel azoles featuring thieno[2,3-c]pyrrolidone and thieno[3,2-c]pyrrolidone nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SARs of antifungal triazoles. Most of target compounds exhibited excellent activity against Candida and Cryptococcus spp., with MIC values in the range of 0.0625 μg/ml to 0.0156 μg/ml. The thieno[3,2-c]pyrrolidone unit was more suited for improving activity against Aspergillus spp. The most potent compound, 18a, was selected for further development due to its significant in vitro activity against Aspergillus spp. (MIC Combining double low line 0.25 μg/ml), as well as its high metabolic stability in human liver microsomes.

Orally active azole derivatives

The present invention relates to new orally active azole derivatives with antifungal activity of formula I STR1 wherein: X is CH or N; Ar represents phenyl substituted with halogen and/or trifluoromethyl; Z is --C(=O)-- or --SO2 --; R1 is CN, CO2 H, CO2 R7, CONR8 R9 or CH2 Y and then R3 is hydrogen, or R1 together with R3 forms a ring of formula I' STR2 wherein B is O, hydroxy or hydrogen; R4 is C1-4 alkyl; R5, R6, R8 and R9 are hydrogen or C1-4 alkyl; Y is --OH, --OR7, --OC(=O)R7, --NR8 R9, --NHC(=O)OR7 ; R7 is C1 -C4 -alkyl, phenyl-C1 -C4 -alkyl or optionally substituted phenyl; when Z is --C(=O)--, R2 is optionally susbtituted phenyl, or naphtyl; when Z is --SO2 --, R2 is C1-4 alkyl, phenyl-C1-4 -alkyl or optionally susbtituted phenyl.

Aldol condensation of Evans chiral enolates with acetophenones. Its application to the stereoselective synthesis of homochiral antifungal agents

The results of the aldol condensation of Evans chiral imide enolates with a series of acetophenones are reported. Activated acetophenones, such as 2,4-difluoroacetophenone, α-chloroacetophenone, and α-chloro- and α-bromo-2,4-difluoroacetophenone, reacted with the lithium enolate of 5 with good levels of enolate facial diastereoselectivity toward the (2R)-isomers (> 10:1) but with low anti: syn selectivity (ca. 3:2). Sodium and potassium enolates of 5 were also tested. The nature of the solvent influenced the degree of diastereofacial biases. Less activated ketones, such as acetophenone, reacted only to a ca. 50% extent without facial or anti:syn stereoselectivities. Chairlike pericyclic transition states are believed to govern the reaction. When α-bromoacetophenones were used, longer reaction times and higher temperatures resulted in the selective formation of the S2 epoxide (syn(2R,3R), 11) with good levels of selectivity. Equilibration studies performed in THF with the corresponding metal aldolates generated in situ by deprotonation of the aldol adducts indicated that an aldol/retroaldol process was first established followed by a slower formation of the epoxide. Stereoselection is thought to originate by a faster oxirane formation of the syn bromohydrins as compared to the anti due to steric interactions between the α-group and the leaving bromide. Optimum retroaldol-epoxide formation rates were obtained using the sodium enolate in ether at -78°C. Under these conditions the S1:S2:A1:A2 ratio of epoxides was 6:83:10:0.3 and the major isomer was isolated by recrystallization in 79% yield. An improved synthesis of amino alcohol 3, an advanced intermediate in the preparation of orally active antifungal agents, using a tandem of this new ketone-aldol technology and a Curtius rearrangement, is reported. The new sequence proceeds with an overall yield of 53% and does not require chromatographic purifications.

Triazole antifungals. IV. Synthesis and antifungal activities of 3-acylamino-2-aryl-2-butanol derivatives

New triazole compounds were designed and synthesized as potential inhibitors of the fungal cytochrome P-450 14α-demethylase. In testing for antifungal activity against a mouse systemic Candida albicans infection, (2R,3R)3-acylamino-2-aryl-2-butanol deriva