91487-86-4

Usage

Uses

Used in Dermatology:
(S)-Bifonazole is used as a topical antifungal agent for the treatment of various skin fungal infections, such as athlete's foot, ringworm, and jock itch. Its application helps in inhibiting the synthesis of ergosterol, which is essential for the integrity of fungal cell membranes, thereby disrupting the growth and reproduction of the fungus and leading to the clearance of the infection.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, (S)-Bifonazole is utilized as an active ingredient in the formulation of antifungal medications. Its incorporation into creams, ointments, or lotions allows for targeted treatment of skin fungal infections with minimal systemic absorption, ensuring a low risk of adverse effects and high patient compliance.

Upstream product

• 288-32-4 1H-imidazole 
• 7515-73-3 4-(chlorophenylmethyl)-1,1'-biphenyl 
• 18156-74-6 1-(Trimethylsilyl)imidazole 
• 7598-80-3 4-phenylbenzhydrol 
• 530-62-1 1,1'-carbonyldiimidazole 
• 768-32-1 trimethylphenylsilane 
• 1063965-82-1 (4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl)(phenyl)methanone 
• 2128-93-0 biphenyl-4-yl-phenyl-methanone 
• 100-58-3 phenylmagnesium bromide 
• 3218-36-8 4-Phenylbenzaldehyde 
• 18282-51-4 4-iodo-benzyl alcohol 
• 3597-91-9 biphenyl-4-yl methanol 
• 98-80-6 phenylboronic acid 
• 50-00-0 formaldehyd 

Relevant academic research and scientific papers

Controlling Multiple Active Sites on Pd?CeO2 for Sequential C?C Cross-coupling and Alcohol Oxidation in One Reaction System

Ceria (CeO2)-supported metal catalysts have been widely utilized for various single-step chemical transformations. However, using such catalysts for a multistep organic reaction in one reaction system has rarely been achieved. Here, we investigate multiple active sites on Pd?CeO2 catalysts and optimize them for a multistep reaction of C?C cross-coupling and alcohol oxidation. Atomic-level imaging and spectroscopic studies reveal that metallic Pd0 and Pd?CeO2 interface are active sites on Pd?CeO2 for C?C cross-coupling and oxidation, respectively. These active sites are controlled under the structural evolution of Pd?CeO2 during reductive heat-treatments. Accordingly, we found that optimally reduced Pd?CeO2 catalysts containing ～1.5 nm-sized Pd nanoclusters with both sites in balance are ideal for multistep chemical transformations in one reaction system. Our strategy to design supported metal catalysts leads to one-pot sequential synthetic protocols for pharmaceutical building blocks.

NHC-Nickel Catalyzed C-N Bond Cleavage of Mono-protected Anilines for C-C Cross-Coupling

A Ni-catalyzed aryl C-N bond cleavage of mono-protected anilines, N-arylsulfonamides, has been developed. A new N-heterocyclic carbene derived from benzoimidazole shows high reactivity for the C-N cleavage/C-C cross-coupling reaction. The ortho-directing group is not required to break the C-N bond of sulfonyl-protected anilines, which are not limited to π-extended anilines. The mechanistic studies have revealed that a sulfamidomagnesium salt is the key coupling intermediate.

Preparation method of para-substituted aryl compound

The invention discloses a preparation method of a para-substituted aryl compound shown as a formula (I) which is described in the specfication. The preparation method is characterized by comprising the following step of: subjecting an aryl sulfonium salt shown as a formula (II) which is described in the specfication and boride to a coupling reaction in a solvent in an inert atmosphere under the action of alkali and a palladium catalyst to obtain the para-substituted aryl compound. According to the method, mono-substituted aromatic hydrocarbon is taken as a substrate, the aryl sulfonium salt isconstructed in situ, and the palladium catalyst catalyzes the aryl sulfonium salt constructed in situ to undergo the Suzuki-Miyaura coupling reaction, so a mono-substituted aromatic hydrocarbon para-arylation or alkenylation product is constructed quickly and efficiently. The method is mild in conditions, high in substrate universality and wide in tolerance of a heterocyclic coupling substrate.

para-Selective arylation and alkenylation of monosubstituted arenes using thianthreneS-oxide as a transient mediator

Using thianthreneS-oxide (TTSO) as a transient mediator,para-arylation and alkenylation of mono-substituted arenes have been demonstratedviaapara-selective thianthrenation/Pd-catalyzed thio-Suzuki-Miyaura coupling sequence under mild conditions. This reaction features a broad substrate scope, and functional group and heterocycle tolerance. The versatility of this approach was further demonstrated by late-stage functionalization of complex bioactive scaffolds, and direct synthesis of some pharmaceuticals, including Tetriprofen, Ibuprofen, Bifonazole, and LJ570.

HPLC method for separating enantiomers of imidazole derivatives - Antifungal compounds

The aim of this study was to test separation possibility of enantiomers of nine active substances belonging to imidazole derivatives: bifonazole, butoconazole, econazole, enilconazole, fenticonazole, isoconazole, miconazole, sertaconazole and tioconazole. The study was performed using HPLC method and the CHIRALCEL OJ column (10 μm; 250 × 4.6 mm), the mobile phase flow rate of 0.8 mL/min and detection at 220 nm. Mobile phases containing hexane and the following modifiers: alcohols (2-propanol, ethanol, methanol) and diethylamine were tested. At first isocratic elution was used but some enantiomers eluted after a long retention time and their peaks were asymmetrical and too wide. Therefore, a gradient elution was developed allowing to obtain satisfactory retention times and other parameters of enentioseparation of the compounds.

Design and Synthesis of Chiral Diene Ligands for RhI-Catalyzed Enantioselective Arylation of N-DPP-protected Aldimines: Synthesis of the Antifungal Agent Bifonazole

Herein we describe the design and synthesis of a novel family of bifunctional, chiral bicyclo[2.2.1]heptadiene ligands bearing aryl and secondary amido groups, and demonstrate their usefulness in the RhI-catalyzed enantioselective addition reaction of arylboronic acids to N-diphenylphosphinyl (N-DPP)-protected aldimines. Unlike the analogous RhI-catalysts comprising diene ligands substituted with aryl and carboxylic ester groups, or only with aryl groups, the addition reaction proceeded with high stereoselectivity. The protocol tolerated a range of N-DPP-aldimines and arylboronic acids, producing the desired optically active N-DPP-protected amines with yields between 31–99 % and with ee values up to 91–99 %. The synthetic utility of the method was demonstrated by the conversion of N-DPP-protected amine 3 ae into the antifungal agent, bifonazole (13).

One-pot process for preparing bifonazole

The invention relates to the technical field of medicine synthesis and in particular relates to a one-pot process for preparing bifonazole. According to the process disclosed by the invention, 4-phenyl benzhydrol is prepared by reducing 4-phenyl benzophenone by potassium borohydride, and a catalyst is added without treatment; and the 4-phenyl benzhydrol is reacted with imidazole in the presence of the catalyst so as to prepare the bifonazole. According to the method disclosed by the invention, the bifonazole with the yield of 76-82% can be obtained. The process disclosed by the invention is simple, less in steps, convenient to operate, does not need any special equipment, is suitable for large-scale industrial production, high in product yield and low in cost, and is obviously improved relative to other processes.

Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17α-hydroxylase-17,20-lyase (CYP17)-Part II: Core rigidification and influence of substituents at the methylene bridge

Thirty-five novel substituted imidazolyl methylene biphenyls have been synthesized as CYP17 inhibitors for the potential treatment of prostate cancer. Their activities have been tested with recombinant human CYP17 expressed in Escherichia coli. Promising compounds were tested for selectivity against CYP11B1, CYP11B2, and hepatic CYP enzymes 3A4, 1A2, 2B6 and 2D6. The core rigidified compounds (30-35) were the most active ones, being much more potent than Ketoconazole and reaching the activity of Abiraterone. However, they were not very selective. Another rather potent and more selective inhibitor (compound 23, IC50 = 345 nM) was further examined in rats regarding plasma testosterone levels and pharmacokinetic properties. Compared to the reference Abiraterone, 23 was more active in vivo, showed a longer plasma half-life (10 h) and a higher bioavailability. Using our CYP17 homology protein model, docking studies with selected compounds were performed to study possible interactions between inhibitors and amino acid residues of the active site.

Practical syntheses of enantiomerically pure N-acetylbenzhydrylamines

Two practical routes for the synthesis of benzhydrylamine derivatives in enantiomerically pure form have been developed. N-Acetylbenzhydrylamines can be synthesised in few steps and good yields starting from 1-aryl-1-propargylamines. The key steps are rep