15017-52-4

Usage

Uses

scaffold molecule for combinatorial synthesis

InChI:InChI=1/C7H5BrFNO2/c8-4-5-1-2-6(9)7(3-5)10(11)12/h1-3H,4H2

Upstream product

• 459-57-4 4-fluorobenzaldehyde 
• 2857-97-8 trimethylsilyl bromide 
• 20274-69-5 (4-fluoro-3-nitrophenyl)methanol 
• 459-56-3 4-fluorobenzylic alcohol 
• 453-71-4 3-nitro-4-fluorobenzoic acid 
• 42564-51-2 4-fluoro-3-nitrobenzaldehyde 
• 446-11-7 4-fluoro-3-nitrotoluene 

Downstream Products

• 157662-77-6 2-(4-fluoro-3-nitrophenyl)acetonitrile 
• 160877-38-3 diethyl 2-(4'-fluoro-3'-nitrophenyl)methylmalonate 
• 169825-20-1 (3R,6S)-2,5-dimethoxy-6-isopropyl-3-(4-fluoro-3-nitrophenyl)-3,6-dihydro-1,4-pyrazine 
• 178217-05-5 (R)-2-(Benzhydrylidene-amino)-3-(4-fluoro-3-nitro-phenyl)-propionic acid tert-butyl ester 
• 20367-99-1 ethyl 2-(acetylamino)-2-(ethoxycarbonyl)-3-(4'-fluoro-3'-nitrophenyl)propanoate 
• 178744-39-3 L-4-fluoro-3-nitrophenylalanine methyl ester 
• 1053615-62-5 (3aS,4R,8R,8aS)-4,8-Dibenzyl-5-(4-fluoro-3-nitro-benzyl)-2,2-dimethyl-7-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazol-5-ylmethyl]-hexahydro-1,3-dioxa-5,7-diaza-azulen-6-one 
• 221123-51-9 4-fluoro-3-nitrobenzyl iodide 
• 389634-80-4 2-(4-fluoro-3-nitro-benzyl)-2-formylamino-malonic acid diethyl ester 
• 945531-26-0 (4S,5R)-3-[(R)-2-(4-fluoro-3-nitrobenzyl)-4-methoxy-3-(4-methoxyphenyl)-5-oxotetrahydrofuran-2-carbonyl]-4-methyl-5-phenyl-2-oxazolidinone 
• 160877-40-7 3-(4-fluoro-3-nitrophenyl)propionic acid 
• 221123-52-0 1-(4-fluoro-3-nitrophenyl)-7-(3-hydroxy-4-methoxyphenyl)heptan-3-one 
• 197382-92-6 2-(4-fluoro-3-nitrobenzyl)-7-(3-isopropoxy-4-methoxyphenyl)-3-oxoheptanoic acid methyl ester 
• 197382-99-3 aceroside IV perbenzoate 

Relevant academic research and scientific papers

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.

p27 PROTEIN INDUCER

The present invention provides a p27 protein inducing agent comprising a compound represented by general formula (11) below or pharmaceutically acceptable salt thereof as an active ingredient: wherein G 1 , G 2 , G 3 and G 8 are each independently selected from -N= etc., Ring G 6 is selected from divalent aryl etc., A is selected from amino etc., G 4 is selected from oxygen etc., G 5 is selected from oxygen etc., G 7 is selected from -CH 2 - etc., and R 2 is selected from C 1-6 alkyl etc.

4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole and -pyrazole derivatives as potent and selective inhibitors of transforming growth factor-β type i receptor kinase

A series of 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2- yl)imidazoles and -pyrazoles 14a-c, 15a-c, 16a, 16b, 19a-d, 21a, and 21b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. Among them, the pyrazole derivative 21b inhibited ALK5 phosphorylation with an IC50 value of 0.018 μM and showed 95% inhibition at 0.03 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct. The 21b showed a high selectivity index of 284 against p38α MAP kinase. The binding pose of 21b generated by docking analysis reveals that it fits well into the ATP binding cavity of ALK5 by forming several hydrogen bond interactions.

Discovery of N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin- 2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline (EW-7197): A highly potent, selective, and orally bioavailable inhibitor of TGF-β type I receptor kinase as cancer immunotherapeutic/antifibrotic agent

A series of 2-substituted-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6- methylpyridin-2-yl)imidazoles was synthesized and evaluated to optimize a prototype inhibitor of TGF-β type I receptor kinase (ALK5), 6. Combination of replacement of a quinoxalin-6-yl moiety of 6 with a [1,2,4]triazolo[1,5-a] pyridin-6-yl moiety, insertion of a methyleneamino linker, and a o-F substituent in the phenyl ring markedly increased ALK5 inhibitory activity, kinase selectivity, and oral bioavailability. The 12b (EW-7197) inhibited ALK5 with IC50 value of 0.013 μM in a kinase assay and with IC50 values of 0.0165 and 0.0121 μM in HaCaT (3TP-luc) stable cells and 4T1 (3TP-luc) stable cells, respectively, in a luciferase assay. Selectivity profiling of 12b using a panel of 320 protein kinases revealed that it is a highly selective ALK5/ALK4 inhibitor. Pharmacokinetic study with 12b·HCl in rats showed an oral bioavailability of 51% with high systemic exposure (AUC) of 1426 ng × h/mL and maximum plasma concentration (Cmax) of 1620 ng/mL. Rational optimization of 6 has led to the identification of a highly potent, selective, and orally bioavailable ALK5 inhibitor 12b.

NOVEL COMPOUNDS FOR MODULATION OF ROR-GAMMA ACTIVITY

The present invention relates to aryl sulfones and related compounds that are modulators of ROR-gamma receptors. The invention also provides pharmaceutical compositions comprising these modulators, and methods of modulating ROR-gamma receptors using them. Also provided are methods of using aryl sulfones and related compounds as modulators of ROR-gamma to treat ROR-gamma mediated diseases

COUMARIN DERIVATIVE, PHARMACEUTICAL COMPOSITION AND USE THEREOF

The present invention relates to a coumarin derivative of formula (I): wherein X, Y1, Y2, Y3, R1, R2, R3 and R4 are as defined herein, or a pharmaceutically acceptable salt or so

Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-methoxy-5-[(2′,4′,6′-trimethoxystyrylsulfonyl)methyl] phenylamino}acetate (ON 01910.Na): Synthesis, structure-activity relationship, and biological activity

Cyclin D proteins are elevated in many cancer cells, and targeted deletion of cyclin D1 gene in the mammary tissues protects mice from breast cancer. Accordingly, there is an increasing awareness of this novel nonenzymatic target for cancer therapeutics. We have developed novel, nonalkylating styrylbenzylsulfones that induce cell death in wide variety of cancer cells without affecting the proliferation and survival of normal cells. The development of derivatized styrylbenzylsulfones followed logically from a tumor cell cytotoxicity screen performed in our laboratory that did not have an a priori target profile. Modifications of some of the precursor molecules led to lead optimization with regard to tumor cell cytotoxicity. In this report we describe the synthesis and structure-activity relationships of novel, nonalkylating (E)-styrylbenzylsulfones and the development of the novel anticancer agent sodium (E)-2-{2-methoxy-5-[(2′,4′,6′- trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na), which is in phase III trials for myelodysplastic syndromes (MDS) associated with aberrant expression of cyclin D proteins.

Efficient and diversity-oriented total synthesis of Riccardin C and application to develop novel macrolactam derivatives

Riccardin C (RC, 1) is a macrocyclic bis(bibenzyl) natural product exhibiting remarkable biological activity as a nuclear liver X receptors (LXRs) ligand and a lipid metabolism mediator. RC is expected to be a lead compound to develop drugs for atherosclerotic diseases, and therefore exploiting diversity-oriented synthesis of RC is a promising approach to drug discovery. In this paper, we report novel total synthesis of RC (7.4% overall yield in 16 steps) by using the intramolecular SNAr reaction as key cyclization reaction. This is the first example of efficient macrocyclization using 3-nitro-4-fluorostilbene as an electrophile. The methodology could be applied to synthesize novel lactam analogs of RC. The diversity-oriented synthesis of RC is versatile method for the synthesis of various types of bis(bibenzyl) natural products and their derivatization.

Total synthesis of plagiochin D by an intramolecular SNAr reaction

The total synthesis of plagiochin D, a macrocyclic bis(bibenzyl) compound isolated from the liverwort plagiochila acanthophylla, has been accomplished. Closure of the key 16-membered ring, which contained biphenyl ether and biaryl units, was achieved in good yield by an intramolecular SNAr reaction. The Suzuki and Wittig protocols proved to be powerful tools for the construction of a linear precursor that was crucial for ring cyclization. Copyright