3723-70-4

Upstream product

• 5470-18-8 2-Chloro-3-nitropyridine 
• 100-46-9 benzylamine 
• 54231-33-3 3-bromo-2-nitropyridine 
• 140-75-0 para-fluorobenzylamine 

Downstream Products

• 61532-32-9 3-(Phenylmethyl)-3H-imidazo<4,5-b>pyridine 
• 1402939-00-7 3-(benzyl)-2-phenyl-3H-imidazo[4,5-b]pyridine 

Relevant academic research and scientific papers

Design, synthesis and characterization of novel N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors leading to the identification of the selective compound, AC1903

The transient receptor potential cation channel 5 (TRPC5) has been previously shown to affect podocyte survival in the kidney. As such, inhibitors of TRPC5 are interesting candidates for the treatment of chronic kidney disease (CKD). Herein, we report the synthesis and biological characterization of a series of N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors. Work reported here evaluates the benzimidazole scaffold and substituents resulting in the discovery of AC1903, a TRPC5 inhibitor that is active in multiple animal models of CKD.

1,2,3-Triazole fused with pyridine/pyrimidine as new template for antimicrobial agents: Regioselective synthesis and identification of potent N-heteroarenes

The 1,2,3-triazole ring fused with pyridine/pyrimidine was explored as new template for the identification of potential antimicrobial agents. The regioselective synthesis of these pre-designed N-heteroarenes was achieved via exploring the application of Buchwald's strategy (i.e. C–N bond formation/reduction/diazotization/cyclization sequence) to the N-heteroarene system. Two of them showed promising antibacterial (comparable to streptomycin) and several showed potent antifungal (comparable to mancozeb) activities.

AUTOTAXIN INHIBITORY COMPOUNDS

The present invention relates to compounds of formula I, wherein A1, A2, A3, R1, R2, R3, R4, R5, R6, L, Ar and Q are each as defined herein. The compounds of the present invention are inhibitors of autotaxin (ATX) enzyme activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions (e.g. fibrosis) in which ATX activity is implicated.

Discovery of potent inhibitors of the lysophospholipase autotaxin

The autotoxin–lysophosphatidic acid (ATX–LPA) axis has been implicated in several disease conditions including inflammation, fibrosis and cancer. This makes ATX an attractive drug target and its inhibition may lead to useful therapeutic agents. Through a high throughput screen (HTS) we identified a series of small molecule inhibitors of ATX which have subsequently been optimized for potency, selectivity and developability properties. This has delivered drug-like compounds such as 9v (CRT0273750) which modulate LPA levels in plasma and are suitable for in vivo studies. X-ray crystallography has revealed that these compounds have an unexpected binding mode in that they do not interact with the active site zinc ions but instead occupy the hydrophobic LPC pocket extending from the active of ATX together with the occupying the LPA ‘exit’ channel.

Amino Azaxylylenes Photogenerated from o-Amido Imines: Photoassisted Access to Complex Spiro-Poly-Heterocycles

Upon irradiation, cyclic imines containing o-amido groups are shown to produce reactive intermediates, amino azaxylylenes, which undergo intramolecular cycloadditions to tethered unsaturated pendants to yield complex N,O-heterocycles having an additional spiro-connected nitrogen heterocyclic moiety. Modular assembly of the photoprecursors allows expeditious increase of the complexity of the target poly-heterocyclic scaffolds with a minimal number of experimentally simple reaction steps. The photocyclization and subsequent postphotochemical transformations are accompanied by an increase of Lovering's fsp3 factor, thus producing unprecedented three-dimensional molecular architectures, and offering extended sampling of chemical space. Rings in three dimensions: Cyclic imines containing an o-amido group undergo excited-state intramolecular proton transfer to generate amino azaxylylenes. The amino azaxylylenes undergo intramolecular cycloadditions to tethered unsaturated pendants to yield complex heterocyclic three-dimensional molecular architectures.

Synthesis and potent cytotoxicity of some novel imidazopyridine derivatives against MCF-7 human breast adenocarcinoma cell line

[Figure not available: see fulltext.] A series of novel 2-phenyl-3H-imidazo[4,5-b]pyridines and 2-phenyl-3H-imidazo[4,5-c]pyridines and their precursors were synthesized. Their in vitro cytotoxicity against MCF-7 human breast adenocarcinoma cell line has been investigated, and some of the tested compounds have shown high cytotoxic activity against MCF-7 cells. N-Hydroxy-4-(3H-imidazo[4,5-b]pyridin-2-yl)benzenecarboximidamide was the most active compound with IC50 equal to 0.082 μM, which is an activity almost as high as that of a commonly used anticancer drugs docetaxel and imatinib mesylate.

Imidazopyridines: A novel class of hNav1.7 channel blockers

A series of imidazopyridines were evaluated as potential sodium channel blockers for the treatment of neuropathic pain. Several members were identified with good hNav1.7 potency and excellent rat pharmacokinetic profiles. Compound 4 had good efficacy (52% and 41% reversal of allodynia at 2 and 4 h post-dose, respectively) in the Chung rat spinal nerve ligation (SNL) model of neuropathic pain when dosed orally at 10 mg/kg.

A COMPOSITION FOR TREATING OR PREVENTING A CANCER COMPRISING PYRROLOPYRIDINE DERIVATIVES

The present invention provides a composition for treating or preventing a cancer comprising a pyrrolopyridine derivative or its salt and a pharmaceutically acceptable carrier.

Nucleophilic substitution reaction of amines with 3-bromo-4-nitropyridine (and 2-nitropyridine): A new nitro-group migration

On the reaction 3-bromo-4-nitropyridine with amine, three in stead of two expected products are separated. 2D NMR spectral data indicate the major product was an unexpected nitro-group migration product. To explore the rearrangement mechanism, a systematic study with various solvents and bases was undertaken. Results obtained indicate that nitro-group migration occurs in polar aprotic solvents; while expected nucleophilic substitution took place under all tested conditions.

Synthesis of N-alkoxybenzimidazoles and N-alkoxypyrimidazoles

A variety of novel N-alkoxy aromatic-fused imidazoles have been prepared in a simple two-step process from 2-fluoro nitroaromatics and 2-chloro-3-nitropyridine. The imidazole forming step involves tandem heterocyclisation and O-alkylation with an in situ alkylating agent, and supports prior mechanistic proposals. Additional mechanistic experiments are described. The protocol is versatile with respect to both substrate halo-nitro aromatics and to the nature of the added electrophile (halides) used in the second step, and thereby significantly extends the scope of this reaction and its applicability to diverse synthesis. This methodology can also be used to generate various types of novel N-alkoxypyrimidazoles (4-deazapurine analogues), and an X-ray structure of one such pyrimidazole is presented.