71897-07-9

Usage

Uses

Used in Pharmaceutical Industry:
AG 1295 is used as an antiproliferative agent for the treatment of diseases such as atherosclerosis, pulmonary fibrosis, and gliomas. Its ability to inhibit PDGF receptor kinase makes it a potential therapeutic option for these conditions.
Used in Research Applications:
AG 1295 is used as a research tool in vitro and in Swiss 3T3 cells, where it has demonstrated the ability to inhibit PDGF-stimulated DNA synthesis with an IC50 value of 2.5 μM. This selective inhibition of PDGF receptor kinase without affecting the activity of the EGF receptor makes it a valuable compound for studying the role of PTKs in cellular processes and disease progression.

in vitro

the previous study investigated the effect of pdgf receptor-beta (pdgfr-β) inhibition by ag-1295 on the osteogenic differentiation of the mouse pre-osteoblastic cell line mc3t3-e1. results showed that ag-1295 could significantly increase the alkaline phosphatase (alp) activity and enhance the formation of mineralized nodules dose-dependently. moreover, the treatment with ag-1295 led to the up-regulated mrna expression of the osteogenic marker genes collagen type i, runt-related transcription factor 2, osterix, tissue-nonspecific alkaline phosphatase, as well as osteocalcin. consistent with its effect on osteoblast differentiation, ag-1295 was also able to significantly suppress the phosphorylation of erk1/2 in mc3t3-e1 cells [1].

in vivo

a previous animal study was designed to evaluated the possible effects of ag1295 on the development of interstitial fibrosis in rats with unilateral ureteral obstruction, monitored by ed-a+ fibronectin expression, the number of macrophages. results showed that the i.p.treatment with ag1295 at 12 mg/kg could significantly reduce interstitial fibrosis as verified by a smaller sirius-red stained area and also by a reduced number of macrophages, and by the ed-a+ fibronectin deposition and the number of cells positive for α-smooth muscle actin [2].

IC 50

0.3-1 μm for pdgf receptor kinase in vitro and in swiss 3t3 cells

references

[1] zhang yy, cui yz, luan j, zhou xy, zhang gl, han jx. platelet-derived growth factor receptor kinase inhibitor ag-1295 promotes osteoblast differentiation in mc3t3-e1 cells via the erk pathway. biosci trends. 2012 jun;6(3):130-5. [2] ludewig d, kosmehl h, sommer m, bhmer fd, stein g. pdgf receptor kinase blocker ag1295 attenuates interstitial fibrosis in rat kidney after unilateral obstruction. cell tissue res. 2000 jan;299(1):97-103.

InChI:InChI=1/C16H14N2/c1-11-8-14-15(9-12(11)2)18-16(10-17-14)13-6-4-3-5-7-13/h3-10H,1-2H3

Upstream product

• 54607-00-0 2-phenyl-3-(toluene-4-sulfonyl)-oxirane 
• 3171-45-7 4,5-dimethyl-1,2-phenylenediamine 
• 1074-12-0 phenylglyoxal hydrate 
• 79866-34-5 2,2-di-(4-methylanilino)-1-phenylethanone 
• 89804-69-3 2,2-di-(4-methoxyanilino)-1-phenylethanone 
• 66749-88-0 2,2-dianilino-1-phenylethanone 
• 89804-70-6 2,2-di-(2-methylanilino)-1-phenylethanone 
• 582-24-1 1-phenyl-2-hydroxyethanone 
• 93-56-1 phenylethane 1,2-diol 
• 93-55-0 1-phenyl-propan-1-one 
• 3282-32-4 2-diazo-acetophenone 
• 122-78-1 phenylacetaldehyde 
• 98-86-2 acetophenone 
• 4636-16-2 iodoacetophenone 

Downstream Products

• 1296867-33-8 C₁₈H₁₆N₂O₂ 
• 1374162-21-6 (S)-6,7-dimethyl-2-phenyl-1,2,3,4-tetrahydroquinoxaline 
• 1444302-68-4 2-(2-fluorophenyl)-6,7-dimethylquinoxaline 
• 1420295-66-4 2-(dimethoxymethyl)-6,7-dimethyl-3-phenylquinoxaline 

Relevant academic research and scientific papers

Iron-catalyzed one-pot synthesis of quinoxalines: Transfer hydrogenative condensation of 2-nitroanilines with vicinal diols

Here, we report iron-catalyzed one-pot synthesis of quinoxalines via transfer hydrogenative condensation of 2-nitroanilines with vicinal diols. The tricarbonyl (η4-cyclopentadienone) iron complex, which is well known as the Kn?lker complex, catalyzed the oxidation of alcohols and the reduction of nitroarenes, and the corresponding carbonyl and 1,2-diaminobenzene intermediates were generated in situ. Trimethylamine N-oxide was used to activate the iron complex. Various unsymmetrical and symmetrical vicinal diols were applied for transfer hydrogenation, resulting in quinoxaline derivatives in 49-98% yields. A plausible mechanism was proposed based on a series of control experiments. The major advantages of this protocol are that no external redox reagents or additional base is needed and that water is liberated as the sole byproduct. This journal is

Iron-Catalyzed Hydrogen Transfer Reduction of Nitroarenes with Alcohols: Synthesis of Imines and Aza Heterocycles

A straightforward and selective reduction of nitroarenes with various alcohols was efficiently developed using an iron catalyst via a hydrogen transfer methodology. This protocol led specifically to imines in 30-91% yields, with a good functional group tolerance. Noticeably, starting from o-nitroaniline derivatives, in the presence of alcohols, benzimidazoles can be obtained in 64-72% yields when the reaction was performed with an additional oxidant, DDQ, and quinoxalines were prepared from 1,2-diols in 28-96% yields. This methodology, unprecedented at iron for imines, also provides a sustainable alternative for the preparation of quinoxalines and benzimidazoles.

NaOH-Mediated Direct Synthesis of Quinoxalines from o-Nitroanilines and Alcohols via a Hydrogen-Transfer Strategy

A NaOH-mediated sustainable synthesis of functionalized quinoxalines is disclosed via redox condensation of o-nitroamines with diols and α-hydroxy ketones. Under optimized conditions, various o-nitroamines and alcohols are well tolerated to generate the desired products in 44-99% yields without transition metals and external redox additives.

Ionic-Liquid-Catalyzed Synthesis of Imines, Benzimidazoles, Benzothiazoles, Quinoxalines and Quinolines through C?N, C?S, and C?C Bond Formation

We report the tetramethyl ammonium hydroxide catalyzed oxidative coupling of amines and alcohols for the synthesis of imines under metal-free conditions by utilizing oxygen from air as the terminal oxidant. Under the same conditions, with ortho-phenylene diamines and 2-aminobenzenethiols the corresponding benzimidazoles and benzothiazoles were obtained. Quinoxalines were obtained from ortho-phenylene diamines and 1-phenylethane-1,2-diol, the conditions were then extended to the synthesis of quinoline building blocks by reaction of 2-amino benzyl alcohols either with 1-phenylethan-1-ol or acetophenone derivatives. The formation of C?N, C?S and C?C bonds was achieved under metal-free conditions. A broad range of amines (aromatic, aliphatic, cyclic and heteroaromatic) as well as benzylic alcohols including heteroaryl alcohols reacted smoothly and provided the desired products. The mild reaction conditions, commercially available catalyst, metal-free, good functional-group tolerance, broad range of products (imines, benzimidazoles, benzothiazoles, quinoxalines and quinolines) and applicability at gram scale reactions are the advantages of the present strategy.

Visible light promoted tandem dehydrogenation-deaminative cyclocondensation under aerobic conditions for the synthesis of 2-aryl benzimidazoles/quinoxalines fromortho-phenylenediamines and arylmethyl/ethyl amines

Visible light promoted domino synthesis of 2-aryl benzimidazoles is reported through the reaction ofortho-phenylenediamines and arylmethyl amines under aerobic conditions. The methodology has wide substrate scope and tolerates a wide range of functional groups affording the products in high yields. The use of arylethyl amines instead of arylmethyl amines gives 2-aryl quinoxalines.

A heterogeneous catalytic strategy for facile production of benzimidazoles and quinoxalines from primary amines using the Al-MCM-41 catalyst

This study reports a straightforward heterogeneous catalytic (Al-MCM-41) approach to synthesize nitrogen heterocycle moieties from primary amines under solvent-free conditions. The Al-MCM-41 catalyst was prepared using a hydrothermal method and characterized by various analytical techniques. The probability and limitations of the catalytic methodology were presented with various substrates. The catalytic method grants an attractive route to a wide variety of benzimidazole and quinoxaline moieties with good to excellent yields. The gram scale reaction and reusability (up to five cycles) of the Al-MCM-41 catalyst would greatly benefit industrial applications. This journal is

Iridium-Catalyzed Carbenoid Insertion of Sulfoxonium Ylides for Synthesis of Quinoxalines and β-Keto Thioethers in Water

Sulfoxonium ylides as safe carbene precursors are described for iridium-catalyzed carbene insertions and annulation, providing a facile and green approach to access a variety of quinoxaline derivatives in water. This water-mediated method also allows the preparation of β-keto thioethers under mild condition.

Iridium-Catalyzed [4+2] Annulations of β-Keto Sulfoxonium Ylides and o-Phenylenediamines: Mild and Facile Synthesis of Quinoxaline Derivatives

A synthetic method for quinoxaline derivatives from the [4+2] annulation of β-keto sulfoxonium ylides and o-phenylenediamine by using (Cp*IrCl2)2 catalyst is described. This novel protocol features mild reaction conditions, moderate to excellent yields, wide substrate scope, and high functional-group compatibility. Moreover, this cyclization strategy was successfully applied in late-stage modification for structurally complex bioactive compounds.

Novel green synthesis method for efficiently synthesizing quinoxaline derivative through transition metal catalyzed carbene insertion/cyclization reaction

The invention discloses a novel green synthesis method for efficiently synthesizing a C-N bond and a quinoxaline derivative through a transition metal catalyzed carbene insertion/cyclization reactionby taking pure water as a solvent and sulfur ylide as a carbene donor. Compared with the traditional method, the method has the advantages that the raw materials are easy to obtain, the steps are simple, the use of toxic organic solvents is avoided and the method is a mild, quick, simple, convenient, effective and environment-friendly method for preparing the quinoxaline mother ring and has a wideapplication prospect.

Application of a reusable Co-based nanocatalyst in alcohol dehydrogenative coupling strategy: Synthesis of quinoxaline and imine scaffolds

A nitrogen doped carbon supported cobalt catalyzed efficient synthesis of imines and quinoxaline motifs is reported. Co(OAc)2-Phen/Carbon-800 (Co-phen/C-800) showed the superior reactivity compared to other materials prepared at different temperature, in the synthesis of quinoxalines by the coupling between diamines and diols. Moreover, applying the transfer hydrogenation and acceptorless dehydrogenative coupling strategy, imines and quinoxaline derivatives were synthesized from the nitro compounds. The practical applicability of this protocol was demonstrated by the gram-scale synthesis and the reusability of the catalyst upto 8th cycle. Furthermore, several kinetic experiments were carried out to realize the probable mechanism.