39621-09-5

Upstream product

• 94-02-0 ethyl 3-oxo-3-phenylpropionate 
• 105-56-6 ethyl 2-cyanoacetate 
• 53162-07-5 α-polyfunctional arylmethylenemalonitrile derivative 
• 341511-83-9 2-cyano-5-phenyl-3,5-dioxopentanonitrile 
• 614-27-7 methyl 3-oxo-3-phenylpropionate 
• 107-91-5 cyanoacetic acid amide 
• 98-86-2 acetophenone 
• 14533-87-0 (Z)-ethyl 2-cyano-3-phenylacrylate 
• 41220-29-5 N-carbamoylmethylpyridinium chloride 
• 148238-27-1 (Z)-2-cyano-3-phenylacrylamide 
• 32727-94-9 1-(2-methoxy-2-oxoethyl)pyridin-1-ium bromide 
• 129115-55-5 4-phenyl-2-oxo-3-(1-pyridino)-5-cyano-3,4-trans-1,2,3,4-tetrahydro-6-pyridinolate 
• 100-52-7 benzaldehyde 
• 131387-92-3 3-methoxycarbonyl-1-(1-pyridino)-2-phenyl-1-cyano-1-ethoxycarbonyl-1-propanide 

Downstream Products

• 25341-96-2 4-cyano-3-phenyl-but-3-enoic acid 
• 1299492-98-0 2-chloro-6-(2-(dimethylamino)ethylamino)-4-phenylnicotinonitrile 
• 1299493-05-2 3-amino-6-(2-(dimethylamino)ethylamino)-4-phenylthieno[2,3-b]pyridine-2-carboxylic acid ethyl ester 
• 1299493-10-9 3-amino-6-(2-(dimethylamino)ethylamino)-4-phenylthieno[2,3-b]pyridine-2-carboxylic acid hydrazide 
• 1299492-82-2 3-amino-6-(2-(dimethylamino)ethylamino)-4-phenylthieno[2,3-b]pyridine-2-carboxylic acid (1-methyl-1H-pyrrol-2-yl-methylene)hydrazide 
• 66662-88-2 2-chloro-6-morpholino-4-phenylnicotinonitrile 
• 37860-86-9 2,6-dihydroxy-4-phenylnicotinonitrile 
• 66662-87-1 2,6-dibromo-4-phenyl-nicotinonitrile 

Relevant academic research and scientific papers

Synthesis, solvatochromism, and biological activity of novel azo dyes bearing 2-pyridone and benzimidazole moieties

New azo dyes bearing 2-pyridone and benzimidazole moieties were prepared using diazotization of 4-(1H-benzo[d]imidazol-2-yl)aniline and coupling of the obtained diazonium salt with substituted 3-cyano-2-pyridones. Obtained compounds were characterized via UV-Vis, FT-IR, and 1 H and 13 C NMR spectroscopy as well as by elemental analysis data. The UV-Vis spectra of the synthesized dyes were measured in thirteen solvents of different properties at room temperature. Solvatochromism and tautomerism of novel azo dyes were discussed. An MTT (3,4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide) test was performed to prove the biocompatibility of the investigated dyes. The investigated dyes exhibited satisfying antiproliferative activities against both tumor cell lines, MDA-MB-231 and HCT-116, demonstrating the potent capacity for treatment of tumors.

Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A2AReceptor

In this study, we determined the crystal structure of an engineered human adenosine A2A receptor bound to a partial agonist and compared it to structures cocrystallized with either a full agonist or an antagonist/inverse agonist. The interaction between the partial agonist, belonging to a class of dicyanopyridines, and amino acids in the ligand binding pocket inspired us to develop a small library of derivatives and assess their affinity in radioligand binding studies and potency and intrinsic activity in a functional, label-free, intact cell assay. It appeared that some of the derivatives retained the partial agonist profile, whereas other ligands turned into inverse agonists. We rationalized this remarkable behavior with additional computational docking studies.

The guareschi pyridine scaffold as a valuable platform for the identification of selective PI3K inhibitors

A novel series of 4-aryl-3-cyano-2-(3-hydroxyphenyl)-6-morpholino-pyridines have been designed as potential phosphatidylinositol-3-kinase (PI3K) inhibitors. The compounds have been synthesized using the Guareschi reaction to prepare the key 4-aryl- 3-cyano-2,6-dihydroxypyridine intermediate. A different selectivity according to the nature of the aryl group has been observed. Compound 9b is a selective inhibitor against the PI3Kα isoform, maintaining a good inhibitory activity. Docking studies were also performed in order to rationalize its profile of selectivity.

Design of novel potent inhibitors of human uridine phosphorylase-1: Synthesis, inhibition studies, thermodynamics, and in vitro influence on 5-fluorouracil cytotoxicity

Uridine (Urd) is a promising biochemical modulator to reduce host toxicity caused by 5-fluorouracil (5-FU) without impairing its antitumor activity. Elevated doses of Urd are required to achieve a protective effect against 5-FU toxicity, but exogenous administration of Urd is not well-tolerated. Selective inhibitors of human uridine phosphorylase (hUP) have been proposed as a strategy to increase Urd levels. We describe synthesis and characterization of a new class of ligands that inhibit hUP type 1 (hUP1). The design of ligands was based on a possible SN1 catalytic mechanism and as mimics of the carbocation in the transition state of hUP1. The kinetic and thermodynamic profiles showed that the ligands here presented are the most potent in vitro hUP1 inhibitors developed to date. In addition, a lead compound improved the antiproliferative effects of 5-FU on colon cancer cells, accompanied by a reduction of in vitro 5-FU cytotoxicity in aggressive SW-620 cancer cells.

Solvent and structural effects on the UV-Vis absorption spectra of some 4,6-disubstituted-3-cyano-2-pyridones

A series of 4,6-disubstituted-3-cyano-2-pyridones was synthesized and their UV-Vis absorption spectra were recorded in the region 200-600 nm in the set of selected solvents. The effects of solvent dipolarity/polarizability and solvent-solute hydrogen-bonding interactions on the spectral shifts were analyzed by means of the linear solvation energy relationship concept of Kamlet and Taft. The influence of solvents as well as substituents on the 2-pyridone/2-hydroxypyridine tautomeric equilibration was evaluated. The absorption band maximum of the 2-hydroxypyridine form is found to appear at a shorter wavelength than that of the 2-pyridone form in all investigated solvents. The replacement of the methyl and phenyl groups at position 6 of the pyridone ring, by a hydroxy group, significantly changes the solvatochromic behavior of the investigated pyridones.

Synthesis and pharmacological evaluation of thieno[2,3-b]pyridine derivatives as novel c-Src inhibitors

Among the recently investigated targets for cancer therapy is the c-Src non-receptor tyrosine kinase. Indeed research around deregulated activity of this enzyme has proven its role in tumor progression, while the beneficial effects of c-Src inhibitors in several pathological models has also been demonstrated. We report here the preparation and pharmacological profile of a novel series of c-Src inhibitors that was elaborated around a 3-amino-thieno[2,3-b]pyridine discovered during an HTS campaign. c-Src enzyme inhibition and c-Src inhibition were investigated in a series of related compounds derived from the initial hit. Molecular modeling as well as X-ray studies on one active compound allowed us to hypothesize on ligand orientation and interactions within the ATP hydrophobic pocket. Design and synthesis of structural analogs then led to new ligands possessing quite efficient enzymatic and c-Src inhibition. The structure-activity elements disclosed in this study shed light on the role played by substituents on the thienopyridine ring as well as the impact of other aromatic moieties in the molecule when interacting with the enzyme.

1,4-Diaza-bicyclo[2,2,2]octane as a novel and efficient catalyst for the synthesis of 3,4,6-trisubstituted 2-pyridone derivatives

3,4,6-Trisubstituted 2-pyridone derivatives have been synthesized in good to excellent yields through a condensation reaction of various 1,3-diketones with amides in the presence of 1,4-Diaza-bicyclo[2,2,2]octane (DABCO) at reflux temperature.

Research and development of an efficient process for the construction of the 2,4,5-substituted pyridines of NK-1 receptor antagonists

Roche has identified a 2,4,5-trisubstituted pyridine template for a new class of potent NK1 receptor antagonists. Previous strategies for construction of the pyridine core of these NK-1 receptor antagonists involved functionalization of a 2,5-disubstituted pyridine. We now report on construction of the pyridine core from commodity components. Shestopalov reported the synthesis of trans-4′-aryl-5′-cyano-1′,2′,3′, 4′-tetrahydro-6′-hydroxy-2′-oxo-1,3′-bipyridinium inner salts from 1-(2-amino-2-oxo-ethyl)pyridinium chloride, aromatic aldehydes, and ethyl cyanoacetate in the presence of a base. Reaction of these salts with phosphorus oxychloride affords 4-aryl-3-cyano-2,6-dichloropyridines. These are efficiently converted to nicotinamide precursors of the Roche NK-1 receptor antagonists by regioselective displacement of one chlorine by an amine, hydrogenolysis of the remaining chlorine, and nitrile hydrolysis.

Further studies on the reaction of ethyl benzoylacetate with malononitrile: Synthesis of some novel pyridine and pyridazine derivatives

2-Cyano-5-phenyl-3,5-dioxopentanonitrile undergoes alcoholysis followed by Knoevenagel condensation to afford ethyl 4,4-dicyano-3-phenyl-3-butenoate, a thermo dynamically controlled product, which undergoes cyclization in acid medium to afford 2,6-dihydroxy-4-phenylnicotinonitrile. Some azo derivatives of nicotinonitriles and of 2-aminopyran are described. 5-Arylazo-2-aminopyrans are transformed by acid treatment into pyridazine derivatives, whereas without the arylazo substituent pyridines are obtained.

THE CYCLIZATION REACTIONS OF NITRILES. XXXVI. THE REACTIONS OF FUNCTIONAL DERIVATIVES OF CYANOACETIC ACID WITH 1-STYRYLPYRIDINIUM SALTS AND THE STEREOCHEMISTRY OF THE FORMATION OF 4-ARYL-2-OXO-3-(1-PYRIDINO)-5-CYANO-3,4-TRANS-1,2,3,4-TETRAHYDRO-6-PYRIDINO

The addition of cyanoacetic acid derivatives to 1-styrylpyridinium salts proceeds stereoselectively with the formation of anti-conformers of pyridinium 1,4-ylids, which also cyclize stereoselectively to give 4-aryl-2-oxo-3-(1-pyridino)-5-cyano-3,4-trans-1