76179-40-3

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Chemical Properties

White powder

InChI:InChI=1/C11H13NO3/c13-11(14)9-2-1-3-10(8-9)12-4-6-15-7-5-12/h1-3,8H,4-7H2,(H,13,14)

Upstream product

• 78056-39-0 4,5-difluoro-2-nitroaniline 
• 458-11-7 3,4-difluoroacetanilide 
• 1662-21-1 N-(3,4-difluoro-2-nitrophenyl)acetamide 
• 292145-76-7 4,5-difluoro-5-nitroaniline 
• 7439-89-6 iron 
• 3863-11-4 3,4-difluoroaniline 
• 351520-29-1 3,4-difluoro-5-nitroaniline 
• 2105-61-5 1,2,4-trifluoro-5-nitrobenzene 

Downstream Products

• 123470-47-3 5,6-difluoro-1H-benzo[d]imidazole-2-thiol 
• 91895-29-3 6,7-difluoro-1,4-dihydro-2,3-quinoxalinedione 
• 143154-28-3 2,3-bis(bromomethyl)-6,7-difluoroquinoxaline 
• 176244-21-6 5,6-difluoro-1H-benzo[d]imidazol-2(3H)-one 
• 142356-62-5 5,6-difluoro-1H-benzo[d]imidazol-2-amine 
• 123470-47-3 5,6-Difluoro-1,3-dihydro-benzoimidazole-2-thione 
• 91895-29-3 2,3-dihydroxy-6,7-difluoroquinoxaline 
• 215734-58-0 6,7-Difluoroquinoxaline 
• 76179-41-4 ethyl 6,7-difluoro-3,4-dihydro-3-oxo-2-quinoxaline carboxylate 
• 230953-87-4 6,7-difluoro-3-methylquinoxalin-2(1H)-one 
• 333452-31-6 2-methyl-6,7-difluoroquinoxaline 
• 137690-08-5 6,7-difluoroquinoxaline-2(1H)-one 

Relevant academic research and scientific papers

A comprehensive assessment of a new series of 5′,6′-difluorobenzotriazole-acrylonitrile derivatives as microtubule targeting agents (MTAs)

Microtubules (MTs) are the principal target for drugs acting against mitosis. These compounds, called microtubule targeting agents (MTAs), cause a mitotic arrest during G2/M phase, subsequently inducing cell apoptosis. MTAs could be classified in two groups: microtubule stabilising agents (MSAs) and microtubule destabilising agents (MDAs). In this paper we present a new series of (E) (Z)-2-(5,6-difluoro-(1H)2H-benzo[d] [1,2,3]triazol-1(2)-yl)-3-(R)acrylonitrile (9a-j, 10e, 11a,b) and (E)-2-(1H-benzo[d] [1,2,3]triazol-1-yl)-3-(R)acrylonitrile derivatives (13d,j), which were recognised to act as MTAs agents. They were rationally designed, synthesised, characterised and subjected to different biological assessments. Computational docking was carried out in order to investigate the potential binding to the colchicine-binding site on tubulin. From this first prediction, the di-fluoro substitution seemed to be beneficial for the binding affinity with tubulin. The new fluorine derivatives, here presented, showed an improved antiproliferative activity when compared to the previously reported compounds. The biological evaluation included a preliminary antiproliferative screening on NCI60 cancer cells panel (1–10 μM). Compound 9a was selected as lead compound of the new series of derivatives. The in vitro XTT assay, flow cytometry analysis and immunostaining performed on HeLa cells treated with 9a showed a considerable antiproliferative effect, (IC50 = 3.2 μM), an increased number of cells in G2/M-phase, followed by an enhancement in cell division defects. Moreover, β-tubulin staining confirmed 9a as a MDA triggering tubulin disassembly, whereas colchicine-9a competition assay suggested that compound 9a compete with colchicine for the binding site on tubulin. Then, the co-administration of compound 9a and an extrusion pump inhibitor (EPI) was investigated: the association resulted beneficial for the antiproliferative activity and compound 9a showed to be client of extrusion pumps. Finally, structural superimposition of different colchicine binding site inhibitors (CBIs) in clinical trial and our MDA, provided an additional confirmation of the targeting to the predicted binding site. Physicochemical, pharmacokinetic and druglikeness predictions were also conducted and all the newly synthesised derivatives showed to be drug-like molecules.

METALLOENZYME INHIBITOR COMPOUNDS

Provided are compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

HETEROCYCLIC COMPOUNDS AND USE THEREOF AS MODULATORS OF TYPE III RECEPTOR TYROSINE KINASES

Provided herein are heterocyclic compounds for treatment of CSF1R, FLT3, KIT, and/or PDGFRβ kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.

Trinuclear {Co2+-M3+-Co2+} complexes catalyze reduction of nitro compounds

This work presents synthesis and characterization of trinuclear {Co2+-Co3+-Co2+} and {Co2+-Fe3+-Co2+} complexes with accessible peripheral Co(ii) ions. Both trinuclear complexes function as efficient reusable heterogeneous catalysts for the selective reduction of assorted nitro compounds to the corresponding amines. The mechanistic investigations suggest the involvement of a Co(ii)-Co(i) cycle in the catalysis.

Fluorine-containing 6,7-dialkoxybiaryl-based inhibitors for phosphodiesterase 10 A: Synthesis and in vitro evaluation of inhibitory potency, selectivity, and metabolism

Based on the potent phosphodiesterase 10 A (PDE10A) inhibitor PQ-10, we synthesized 32 derivatives to determine relationships between their molecular structure and binding properties. Their roles as potential positron emission tomography (PET) ligands were evaluated, as well as their inhibitory potency toward PDE10A and other PDEs, and their metabolic stability was determined in vitro. According to our findings, halo-alkyl substituents at position 2 of the quinazoline moiety and/or halo-alkyloxy substituents at positions 6 or 7 affect not only the compounds′ affinity, but also their selectivity toward PDE10A. As a result of substituting the methoxy group for a monofluoroethoxy or difluoroethoxy group at position 6 of the quinazoline ring, the selectivity for PDE10A over PDE3A increased. The same result was obtained by 6,7-difluoride substitution on the quinoxaline moiety. Finally, fluorinated compounds (R)-7-(fluoromethoxy)-6-methoxy-4-(3-(quinoxaline-2-yloxy)pyrrolidine-1-yl) quinazoline (16 a), 19 a-d, (R)-tert-butyl-3-(6-fluoroquinoxalin-2-yloxy) pyrrolidine-1-carboxylate (29), and 35 (IC50 PDE10A 11-65 nM) showed the highest inhibitory potential. Further, fluoroethoxy substitution at position 7 of the quinazoline ring improved metabolic stability over that of the lead structure PQ-10. Fluor your health: Phosphodiesterase 10 A (PDE10A) has emerged as an attractive target for the development of 18F-labelled brain imaging agents for positron emission tomography. A series of fluorinated dialkoxybiaryl compounds were synthesized and evaluated as PDE10A inhibitors, assisted by QSAR docking studies. The 7-fluoromethoxy derivative appears to be a promising candidate for further development.

Fluorinated benzothiadiazole-based conjugated polymers for high-performance polymer solar cells without any processing additives or post-treatments

Thanks to their many favorable advantages, polymer solar cells exhibit great potential for next-generation clean energy sources. Herein, we have successfully designed and synthesized a series of new fluorinated benzothiadiazole-based conjugated copolymers PBDTTEH-DT HBTff (P1), PBDTTEH-DTEHBTff (P2), and PBDTHDO-DTHBTff (P3). The power conversion efficiencies of 4.46, 6.20, and 8.30% were achieved for P1-, P2-, and P3-based devices within ～100 nm thickness active layers under AM 1.5G illumination without any processing additives or post-treatments, respectively. The PCE of 8.30% for P3 is the highest value for the reported traditional single-junction polymer solar cells via a simple fabrication architecture without any additives or post-treatments. In addition, it is noteworthy that P3 also allows making high efficient polymer solar cells with high PCEs of 7.27 and 6.56% under the same condition for ～200 and ～300 nm thickness active layers, respectively. Excellent photoelectric properties and good solubility make polymer P3 become an alternative material for high-performance polymer solar cells.

Structural variation of donor-acceptor copolymers containing benzodithiophene with bithienyl substituents to achieve high open circuit voltage in bulk heterojunction solar cells

Three new donor-acceptor copolymers P1, P2, and P3 were synthesized with benzodithiophene with bithienyl substituents as the donor and 5,6-difluorobenzo[c][1,2,5]thiadiazole, 4,7-di(thiophen-2-yl)benzo[c][1,2,5] thiadiazole, and 5,6-difluoro-4,7-di(thiophen-2-yl)benzo[c][1,2,5]thiadiazole as the acceptors, respectively. The insertion of thiophene spacer between the donor and the acceptor broadened the absorption of the polymers P2 and P3 and resulted in a red shift of ～30 nm as compared to that of the polymer P1. However, the inclusion of fluorine atoms on the polymer had detrimental effects on the photovoltaic properties of the polymers. The synthesized donor-acceptor polymers were tested in bulk heterojunction (BHJ) solar cells with [6,6]-phenyl C71 butyric acid methyl ester (PC71BM) acceptor. Polymer P2 gave a PCE of 3.52% with PC71BM in which the active layer was prepared in chloroform with 3% v/v 1,8-diiodooctane (DIO) additive. The effect of fluorine substitution and thiophene group insertion on the UV/Vis absorbance, photovoltaic performances, morphology, and charge carrier mobilities for the polymers are discussed.

Chemo-enzymatic synthesis and biological evaluation of 5,6-disubstituted benzimidazole ribo- and 2′-deoxyribonucleosides

A number of new 5,6-disubstituted benzimidazoles have been prepared and their substrate properties for recombinant E. coli purine nucleoside phosphorylase (PNP; the product of the deoD gene) in the transglycosylation reaction were investigated. The heterocyclic bases showed good substrate activity for PNP and the ribo- and 2-deoxyribonucleosides were synthesized. The predominant (OMe and OEt) or exclusive (Oi-Pr, morpholino, and N-methylpiperazino) formation of the 5-substituted 6-fluoro-1-(β-d- ribofuranosyl)benzimidazoles was observed. The formation of the regioisomeric 6- methoxy-, 6-ethoxy-, or 6-isopropoxy-substituted 1-(2-deoxy-β-d- ribofuranosyl)-5-fluorobenzimidazoles was observed in the trans-2- deoxyribosylation reaction of the corresponding bases. The predominant or exclusive formation of the regioisomeric N1-nucleosides with bulky 5-substituents of 6-fluorobenzimidazole points to a large hydrophobic pocket in the E. coli PNP active site that can accommodate these groups. The biological activity of the synthesized nucleosides was studied and revealed no inhibitory activity against a broad variety of DNA and RNA viruses. The compounds also lacked significant cytotoxicity. Georg Thieme Verlag Stuttgart New York.

Conjugated side-chain-isolated D-A copolymers based on benzo[1,2-b:4,5-b']dithiophene-alt-dithienylbenzotriazole: Synthesis and photovoltaic properties

Conjugated side-chain-isolated D-A copolymers, based on the donor unit of benzodithiophene (BDT) with a thiophene-conjugated side chain, thiophene π bridge, and the acceptor unit of benzotriazole (BTA) with or without fluorine substitution (PBDT-FBTA and PBDT-HBTA), were designed and synthesized for elucidating their structure-property relationships. The copolymer films demonstrated well-defined absorption peaks with steep absorption edges, consistent with their rigid and ordered structures in the solid films. The substitution of a thiophene-conjugated side chain on the BDT unit in the copolymers aroused 15-nm red-shifted absorption in comparison with its polymer analogues with alkoxy side chains on the BDT unit. Compared to PBDT-HBTA, PBDT-FBTA with two-fluorine-atom substitution on the BTA unit demonstrated a lower highest occupied molecular orbital energy level, higher hole mobility, and significantly better photovoltaic performance. A polymer solar cell (PSC) based on PBDT-FBTA/PC70BM (1:2, w/w) with a 5% 1,8-diiodooctane additive displayed a power conversion efficiency (PCE) of 6.0% with a Jsc of 11.9 mA cm-2, a VOC of 0.75 V, and a fill factor of 67.2%, under the illumination of AM1.5G, 100 mW cm-2. Even at a thicker active layer of 400 nm, the PSC still demonstrated a higher PCE of 4.74%. The results indicate that PBDT-FBTA is a promising polymer donor material for future application of large-area PSCs.

Synthesis of novel histamine H4 receptor antagonists

This letter describes the discovery and synthesis of a series of octahydropyrrolo[3,4-c]pyrrole based selective histamine hH4 receptor antagonists. The amidine compound 20 was found to be a potent and selective histamine H4 receptor antagonist with moderate clearance and a high volume of distribution.