42564-51-2

Usage

Chemical Properties

White to tan crystalline powder

InChI:InChI=1/C7H4FNO3/c8-6-2-1-5(4-10)3-7(6)9(11)12/h1-4H

Upstream product

• 459-57-4 4-fluorobenzaldehyde 
• 453-71-4 3-nitro-4-fluorobenzoic acid 
• 16588-34-4 4-chloro-3-nitro-benzaldehyde 
• 20274-69-5 (4-fluoro-3-nitrophenyl)methanol 
• 20968-47-2 p-(2,2-Dichlorocyclopropyl)fluorobenzene 

Downstream Products

• 3011-34-5 4-hydroxy-3-nitrobenzaldehyde 
• 51818-99-6 4-amino-3-nitro-benzaldehyde 
• 98879-72-2 N-(4-formyl-2-nitro-phenyl)-glycine 
• 109811-80-5 1,N^α-bis-(4-formyl-2-nitro-phenyl)-L-histidine 
• 139080-77-6 α-morpholino-α-(4-morpholino-3-nitro-phenyl)-acetonitrile 
• 311464-46-7 4-fluoro-3-nitro-benzaldehyde dimethyl acetal 
• 391213-68-6 (Z)-methyl 2-(acetylamino)-3-(4-fluoro-3-nitrophenyl)propenoate 
• 501931-57-3 2-nitro-biphenyl-4-carbaldehyde 
• 169825-21-2 D-(4-fluoro-3-nitrophenyl)glycine methyl ester 
• 331731-26-1 (R)-N-(tert-butoxycarbonyl)-4-fluoro-3-nitrophenylalanine methyl ester 
• 391213-74-4 (R)-2-[(R)-2-tert-Butoxycarbonylamino-2-(3-hydroxy-4-methoxy-phenyl)-acetylamino]-3-(4-fluoro-3-nitro-phenyl)-propionic acid methyl ester 
• 391213-76-6 (R)-3-(4-Fluoro-3-nitro-phenyl)-2-[(R)-2-(3-hydroxy-4-methoxy-phenyl)-2-(2,2,2-trifluoro-acetylamino)-acetylamino]-propionic acid methyl ester 
• 391213-84-6 (8S,11R,14R)-11-(4-Fluoro-3-nitro-benzyl)-5,18-dimethoxy-10,13-dioxo-14-(2,2,2-trifluoro-acetylamino)-2-oxa-9,12-diaza-tricyclo[13.3.1.1^3,7]icosa-1⁽¹⁸⁾,3⁽²⁰⁾,4,6,15⁽¹⁹⁾,16-hexaene-8-carboxylic acid 
• 391213-82-4 (8S,11R,14R)-11-(4-Fluoro-3-nitro-benzyl)-5,18-dimethoxy-10,13-dioxo-14-(2,2,2-trifluoro-acetylamino)-2-oxa-9,12-diaza-tricyclo[13.3.1.1^3,7]icosa-1⁽¹⁸⁾,3⁽²⁰⁾,4,6,15⁽¹⁹⁾,16-hexaene-8-carboxylic acid methylamide 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of phenyl urea derivatives as IDO1 inhibitors

Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing intracellular enzyme that catalyzes the first and rate-determining step of tryptophan metabolism and is an important immunotherapeutic target for the treatment of cancer. In this study, we designed and synthesized a new series of compounds as potential IDO1 inhibitors. These compounds were then evaluated for inhibitory activity against IDO1 and tryptophan 2,3-dioxygenase (TDO). Among them, the three phenyl urea derivatives i12, i23, i24 as showed potent IDO1 inhibition, with IC50 values of 0.1–0.6 μM and no compound exhibited TDO inhibitory activity. Using molecular docking, we predicted the binding mode of compound i12 within IDO1. Compound i12 was further investigated by determining its in vivo pharmacokinetic profile and anti-tumor efficacy. The pharmacokinetic study revealed that compound i12 had satisfactory properties in mice, with moderate plasma clearance (22.45 mL/min/kg), acceptable half-life (11.2 h) and high oral bioavailability (87.4%). Compound i12 orally administered at 15 mg/kg daily showed tumor growth inhibition (TGI) of 40.5% in a B16F10 subcutaneous xenograft model and 30 mg/kg daily showed TGI of 34.3% in a PAN02 subcutaneous xenograft model. In addition, the body weight of i12-treated mice showed no obvious reduction compared with the control group. Overall, compound i12 is a potent lead compound for developing IDO1 inhibitors and anti-tumor agents.

Phenylpropionic acid derivatives, and preparation method, pharmaceutical composition and application thereof

The invention discloses phenylpropionic acid derivatives, and a preparation method, a pharmaceutical composition and application thereof. Specifically, the invention relates to the phenylpropionic acid derivatives represented by general formula I, a pharmaceutically acceptable salt and a preparation method thereof, a composition containing one or more of the compounds, and application of the compounds in treatment of diseases related to an IDO signal channel, such as cancers, infectious diseases and autoimmune diseases.

Piperidine compound and preparation method and medical application thereof

The invention discloses a piperidine compound shown as a formula (I) and a preparation method and medical application thereof, and particularly relates to a piperidine USP7 inhibitor compound or pharmaceutically acceptable salt or ester or solvate thereof and a preparation method and application of the piperidine USP7 inhibitor compound or pharmaceutically acceptable salt or ester or solvate thereof. The compound provided by the invention can inhibit the activity of USP7 enzyme, has very good selectivity and druggability, and can be used for preparing medicines for preventing or treating tumor diseases or virus infectious diseases.

New nitro-laterally substituted azomethine derivatives; synthesis, mesomorphic and computational characterizations

Two new homologues series, based on two rings of the azomethine central group bearing the terminal alkoxy group of various chain lengths, were prepared. The alkoxy chain length varied between 6 and 16 carbons. The other terminal wing in the first series was the F atom, and the compound is named N-4-florobenzylidene-4-(alkoxy)benzenamine (In). The second group of compounds included a lateral NO2 substituent in addition to the terminal F atom, named N-(4-fluoro-3-nitrobenzylidene)-4-(alkyloxy)aniline (IIn). Mesomorphic and optical properties were carried out via differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Elemental analyses, FT-IR, and NMR spectroscopy were carried out to elucidate the molecular structures of the synthesized groups. Mesomorphic investigations indicated that all the synthesized homologues (In) were monomorphic, possessing the smectic A (SmA) phase monotropically, while the second group (IIn) members were non-mesomorphic. The experimental data indicated that the formation of the mesophase is affected by the protrusion of the lateral nitro group. The disruption of the mesophase in the second group was attributed to the increase of its molecular width, which affects its lateral intermolecular interactions. The computational simulations were in agreement with the experimental data. On the other hand, the location of NO2 group within the molecular geometry increased the melting temperature of the molecule, and thus, affected their thermal and physical properties. By discussing the estimated parameters, it was found that the molecular architecture, the dipole moment, and the polarizability of the investigated compounds are highly affected by the electronic nature and position of the terminal and lateral substituents as well as their volumes.

COMPOUNDS WITH ANTIMICROBIAL ACTIVITY

Provided herein are compounds useful in the treatment of bacterial infections, pharmaceuticals comprising the same, and methods of use and preparation thereof.

Discovery of Antibacterials That Inhibit Bacterial RNA Polymerase Interactions with Sigma Factors

Formation of a bacterial RNA polymerase (RNAP) holoenzyme by a catalytic core RNAP and a sigma (σ) initiation factor is essential for bacterial viability. As the primary binding site for the housekeeping σ factors, the RNAP clamp helix domain represents an attractive target for novel antimicrobial agent discovery. Previously, we designed a pharmacophore model based on the essential amino acids of the clamp helix, such as R278, R281, and I291 (Escherichia coli numbering), and identified hit compounds with antimicrobial activity that interfered with the core-σ interactions. In this work, we rationally designed and synthesized a class of triaryl derivatives of one hit compound and succeeded in drastically improving the antimicrobial activity against Streptococcus pneumoniae, with the minimum inhibitory concentration reduced from 256 to 1 μg/mL. Additional characterization of antimicrobial activity, inhibition of transcription, in vitro pharmacological properties, and cytotoxicity of the optimized compounds demonstrated their potential for further development.

Biphenyl compound as well as preparation method and medical application thereof

The invention discloses a biphenyl compound as well as a preparation method and medical application thereof, the structure of the biphenyl compound is shown as a formula (I) or a formula (II), and thebiphenyl compound or pharmaceutically acceptable salt, tautomer, meso-isomer, raceme, stereoisomer, metabolite, metabolite precursor, prodrug or solvate thereof is a PD-L1 inhibitor. The compound hasa remarkable inhibiting effect on the interaction of PD-1 and PD-L1 protein, so that the compound can be applied to the preparation of PD-L1 inhibitors and immunomodulator drugs for preventing or treating tumors, autoimmune diseases, organ transplant rejection, infectious diseases and inflammatory diseases.

Design, synthesis and biological evaluation of 2,5-dimethylfuran-3-carboxylic acid derivatives as potential IDO1 inhibitors

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a vital role in tumor immune escape and has emerged as a promising target for cancer immunotherapy. In this study, a novel series of 2,5-dimethylfuran-3-carboxylic acid derivatives were designed, synthesized and evaluated for inhibitory activities against IDO1, and their structure-activity relationship was investigated. Among these, compound 19a exhibited excellent IDO1 inhibitory activity (HeLa cellular IC50 = 4.0 nM, THP-1 cellular IC50 = 4.6 nM). Further molecular docking studies revealed that the compound 19a formed a coordinate bond with the heme iron through the carboxylic acid moiety. These results indicate that compound 19a is a potential IDO1 inhibitor for further investigation.

Heterocycle type derivative and preparing method and pharmaceutical application thereof

The invention relates to a novel heterocycle type derivative, a preparing method thereof, a medicine composition containing the derivative and application of the heterocycle type derivative as therapeutic agent, particularly an FGFR4 inhibitor. The preferable compound has a good inhibiting effect on FGFR4.

Asymmetric Total Synthesis and Evaluation of Antitumor Activity of Ophiorrhisine A and Its Derivatives

The first asymmetric total synthesis of ophiorrhisine A (1), a new cyclic tetrapeptide isolated from Ophiorrhiza nutans, was accomplished via an intramolecular aromatic nucleophilic substitution reaction (IMSNAr) of a linear tripeptide to construct a 14-membered paracyclophane ring, resulting in confirmation of its structure and absolute configuration. The structure-activity relationship study of 1 and its derivatives demonstrated that some derivatives possessed cytotoxicity toward human cancer cell lines A549, HT29, and HCT116.