112559-81-6

Usage

Uses

Used in Pharmaceutical Industry:
4-(4-(4-Nitrophenyl)-1-piperazinyl)phenol is used as a key intermediate in the synthesis of triazole medicines for the treatment of deep department fungal infections. It plays a vital role in the development of antifungal agents that target and cure such infections effectively.
Used in Antifungal Applications:
As a component in the synthesis of triazole medicines like itraconazole (I937500), 4-(4-(4-Nitrophenyl)-1-piperazinyl)phenol is employed as an antifungal agent, specifically against deep department fungal infections. Its incorporation in the development of these medicines aids in the effective treatment and management of such infections.
Used as an Inhibitor of Endothelial Cell Proliferation:
4-(4-(4-Nitrophenyl)-1-piperazinyl)phenol is also used as an inhibitor of endothelial cell proliferation, which can have implications in various medical applications, including the prevention of abnormal blood vessel growth associated with certain diseases.

InChI:InChI=1/C16H17N3O3/c20-16-7-5-14(6-8-16)18-11-9-17(10-12-18)13-1-3-15(4-2-13)19(21)22/h1-8,20H,9-12H2

Upstream product

• 153466-15-0 4-[4-(4-nitro-phenyl)-piperazin-1-yl]-phenylamine 
• 74852-61-2 1-(4-methoxyphenyl)-4-(4-nitrophenyl)-piperazine 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 100-25-4 para-dinitrobenzene 
• 67455-41-8 4-(piperazin-1-yl)aniline 
• 6269-89-2 1-(4-Nitrophenyl)piperazine 
• 56621-48-8 1-(4-hydroxyphenyl)piperazine 
• 350-46-9 4-Fluoronitrobenzene 
• 100-00-5 4-chlorobenzonitrile 
• 104-94-9 4-methoxy-aniline 
• 84145-43-7 1-(para-methoxyphenyl)piperazine hydrochloride 
• 123-30-8 4-amino-phenol 
• 586-78-7 para-nitrophenyl bromide 
• 38212-30-5 4-(4-methoxyphenyl)piperazine 

Downstream Products

• 128063-69-4 2-(2,4-Dichlorophenyl)-3-(4-[4-(4-nitrophenyl)piperazin-1-yl]phenoxy)-1-(1H-1,2,4-triazol-1-yl)propan-2-ol 
• 128063-72-9 2-(2,4-Difluorophenyl)-3-(4-[4-(4-nitrophenyl)piperazin-1-yl]phenoxy)-1-(1H-1,2,4-triazol-1-yl)propan-2-ol 
• 1246819-65-7 1-(4-(methoxymethoxy)phenyl)-4-(4-nitrophenyl)piperazine 
• 1329503-19-6 C₂₅H₂₇N₃O₄ 
• 1339803-88-1 C₁₉H₂₅N₅O₃ 
• 1246815-17-7 4-(4-(4-(methoxymethoxy)phenyl)piperazin-1-yl)aniline 

Relevant academic research and scientific papers

Structure-Activity Relationships for Itraconazole-Based Triazolone Analogues as Hedgehog Pathway Inhibitors

The Food and Drug Administration-approved antifungal agent, itraconazole (ITZ), has been increasingly studied for its novel biological properties. In particular, ITZ inhibits the hedgehog (Hh) signaling pathway and has the potential to serve as an anticancer chemotherapeutic against several Hh-dependent malignancies. We have extended our studies on ITZ analogues as Hh pathway inhibitors through the design, synthesis, and evaluation of novel des-triazole ITZ analogues that incorporate modifications to the triazolone/side chain region of the scaffold. Our overall results suggest that the triazolone/side chain region can be replaced with various functionalities (hydrazine carboxamides and meta-substituted amides) resulting in improved potency when compared to ITZ. Our studies also indicate that the stereochemical orientation of the dioxolane ring is important for both potent Hh pathway inhibition and compound stability. Finally, our studies suggest that the ITZ scaffold can be successfully modified in terms of functionality and stereochemistry to further improve its anti-Hh potency and physicochemical properties.

Preparation method of 4-[4-[4-(4-hydroxyphenyl) piperazine-1-yl] phenyl] phenyl carbamate

The invention discloses a preparation method of 4-[4-[4-(4-hydroxyphenyl) piperazine-1-yl] phenyl] phenyl carbamate, which comprises the following steps: by taking 4-hydroxyaniline as a raw material, carrying out ring closing on the 4-hydroxyaniline and dichloroethylamine hydrochloride to synthesize 1-(4-hydroxyphenyl) piperazine with the purity of 95A% and the correction yield of 80%; 4-nitrochlorobenzene and the prepared 1-(4-hydroxyphenyl) piperazine are coupled to synthesize 4-(4-(4-nitrophenyl)-1-piperazinyl) phenol, the purity is 93 A%, and the correction yield is 88%; then carrying out nitro reduction to synthesize 1-(4-aminophenyl)-4-(4-hydroxyphenyl) piperazine with the purity of 98A% and the correction yield of 77%; and finally, synthesizing 4-[4-[4-(4-hydroxyphenyl) piperazine-1-yl] phenyl] phenyl carbamate with the purity of 98.7%, the content of 98.5 wt% and the correction yield of 83% by using phenyl chloroformate to protect phenolic hydroxyl groups. According to the invention, the high-purity target product 4-[4-[4-(4-hydroxyphenyl) piperazine-1-yl] phenyl] phenyl carbamate can be obtained through easily available raw materials and simple process steps.

Itraconazole-based Smo inhibitor as well as preparation method and application thereof

The invention discloses an itraconazole-based Smo inhibitoras well as a preparation method and application of the Smo inhibitor. The Smo inhibitor has a structural formula shown as a formula (I). The invention also discloses a preparation method and application of the material. According to the invention, itraconazole is used as a lead compound, optimization and transformation are carried out on the basis of the itraconazole, and the Smo inhibitor with good inhibitory activity is obtained.

ANTI-FUNGAL TREATMENT

Provided are compounds, methods, and pharmaceutical compositions useful for treatment of fungal infections, e.g., aspergillosis, candidiasis, cryptococcosis, histoplasmosis, and the like. For example, the pharmaceutical composition may include a pharmaceutically acceptable carrier or excipient, and a compound represented by Ar— C(=NR1)NR2— A---X— Y— Het2 and pharmaceutically acceptable salts thereof. Ar may be an optionally substituted aryl or nitrogen- containing heteroaryl. R1 and R2 may independently be H, optionally substituted C1-C6 aikyi, or optionally substituted C3-C6 cyeloalkyi. A may be a bond or an optionally substituted linking moiety comprising 1, 2, or 3 rings. Each ring in the optionally substituted linking moiety may independently be one of: aryl, cyeloalkyi, heterocycloalkyl, and heteroaryl. X may be O, S, amide, or a bond. Y may be optionally substituted C1-C10 alkyi or optionally substituted C2-C10 alkenyl. Het2 may be an optionally substituted five-membered nitrogen-containing heteroaromatic ring comprising 1, 2, or 3 ring heteroatoms.

ANTI-PARASITIC COMPOUNDS

Provided are compounds, methods, and pharmaceutical compositions useful for treatment of parasites, e.g., Leishmania. For example, the compound may he represented by Ar—C(=NR1)NR2—A—X—Y—Het2, and pharmaceutically acceptable salts thereof. Ar may be an optionally substituted, aryl or nitrogen-containing heteroaryl. R1 and R2 may independently represent H, optionally substituted C1-C6 alkyl, or optionally substituted C3-C6 cycloalkyl. A may be a bond or an optionally substituted linking moiety comprising 1, 2, or 3 rings. Each ring in the optionally substituted linking moiety may independently be one of: aryl, cycloalkyl, heterocycloalkyl, and heteroaryl. X may be O, S, amide, or a bond. Y may be optionally substituted C1-C14 alkyl or optionally substituted C2-C14 alkenyl. Het2 may be an optionally substituted five-membered nitrogen-containing heteroaromatic ring comprising 1, 2, or 3 ring heteroatoms.

Preparation process of posaconazole intermediate 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine

The invention relates to the technical field of chemical medicine synthesis, in particular to a preparation process of posaconazole intermediate 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine. The preparation process provided by the invention comprises the following steps of a, preparing methoxyphenyl piperazine hydrochloride; b, preparing p-hydroxyphenyl piperazine hydrobromide; c, preparing 1-(4-hydroxyphenyl)-4-(4-nitrophenyl)piperazine; d, preparing a crude product of 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine; e, purifying a product. Cheap solvents and high-activity nickel catalystsare selected and used; low-pressure hydrogenation reaction is used; the raw material cost is greatly reduced; important links such as nickel ion removal and aluminum ion removal are used for post treatment; the product quality reaches the content of 99.2 percent; the single maximum noise peak value is less than 0.1 percent; the total noise peak value is less than 1.0 percent; the home and abroadmarket competitive power of the product is greatly enhanced.

Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic

Itraconazole (ITZ) is an FDA-approved member of the triazole class of antifungal agents. Two recent drug repurposing screens identified ITZ as a promising anticancer chemotherapeutic that inhibits both the angiogenesis and hedgehog (Hh) signaling pathways. We have synthesized and evaluated first- and second-generation ITZ analogues for their anti-Hh and antiangiogenic activities to probe more fully the structural requirements for these anticancer properties. Our overall results suggest that the triazole functionality is required for ITZ-mediated inhibition of angiogenesis but that it is not essential for inhibition of Hh signaling. The synthesis and evaluation of stereochemically defined des-triazole ITZ analogues also provides key information as to the optimal configuration around the dioxolane ring of the ITZ scaffold. Finally, the results from our studies suggest that two distinct cellular mechanisms of action govern the anticancer properties of the ITZ scaffold.

Itraconazole Side Chain Analogues: Structure-Activity Relationship Studies for Inhibition of Endothelial Cell Proliferation, Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Glycosylation, and Hedgehog Signaling

Itraconazole is an antifungal drug that was recently found to possess potent antiangiogenic activity and anti-hedgehog (Hh) pathway activity. To search for analogues of itraconazole with greater potency and to understand the structure-activity relationship in both antiangiogenic and Hh targeting activity, 25 itraconazole side chain analogues were synthesized and assayed for inhibition of endothelial cell proliferation and Gli1 transcription in a medulloblastoma (MB) culture. Through this analysis, we have identified analogues with increased potency for inhibiting endothelial cell proliferation and the Hh pathway, as well as VEGFR2 glycosylation that was recently found to be inhibited by itraconazole. An SAR analysis of these activities revealed that potent activity of the analogues against VEGFR2 glycosylation was generally driven by side chains of at least four carbons in composition with branching at the α or β position. SAR trends for targeting the Hh pathway were divergent from those related to HUVEC proliferation or VEGFR2 glycosylation. These results also suggest that modification of the sec-butyl side chain can lead to enhancement of the biological activity of itraconazole.

Mono N-arylation of piperazine(III): Metal-catalyzed N-arylation and its application to the novel preparations of the antifungal posaconazole and its advanced intermediate

A novel application of Pd0-catalyzed arylation to mono N-arylated piperazines, its mechanism, and its application towards the novel syntheses of the key differentially N,N′-diarylated piperazine antifungal intermediate N-(4-hydroxyphenyl)-N′-(4-aminophenyl)piperazine 5 as well as posaconazole 1 are described.