33524-79-7

Upstream product

• 675-10-5 4-hydroxy-6-methyl-2-pyron 
• 100-46-9 benzylamine 
• 143456-22-8 2,2-dimethyl-5-(3-oxobutanoyl)-1,3-dioxane-4,6-dione 
• 130473-38-0 2,2-dimethyl-6-(2-oxo-2-methylethyl)-4H-1,3-dioxin-4-one 
• 847983-06-6 5-[(Z)-3-(benzylamino)-2-butenoyl]-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 84259-92-7 (Z)-N-benzyl-5-(benzylamino)-3-oxohex-4-enamide 
• 847983-10-2 1-benzyl-6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyridine-3-carboxylic acid 

Downstream Products

• 899789-28-7 1-benzyl-4-chloro-6-methyl-2(1H)-pyridinone 
• 899789-26-5 1-benzyl-4-hydrazino-6-methyl-2(1H)-pyridinone 
• 1110533-53-3 1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl propanoate 
• 24681-65-0 3-acetyl-1-benzyl-6-methyl-1,2,3,4-tetrahydropyridine-2,4-dione 
• 586373-00-4 1-benzyl-4-(benzyloxy)-6-methylpyridin-2(1H)-one 
• 586373-04-8 1-benzyl-6-methyl-2-oxo-1,2-dihydropyridin-4-yl-4-bromobenzenesulfonate 
• 265315-77-3 2-amino-6-benzyl-7-methyl-4-(4-nitrophenyl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c]pyridine-3-carbonitrile 

Relevant academic research and scientific papers

Regio- and diastereoselective synthesis of N-substituted 2-acyl-3-aryl-3,5-dihydrofuro[3,2-c]pyridin-4(2H)-ones

[Figure not available: see fulltext.] The three-component condensation of pyridinium acylmethylides generated in situ with aromatic aldehydes and 4-hydroxy-6-methylpyridones gave a series of 2-acyl-3-aryl-3,5-dihydrofuro[3,2-c]pyridin-4(2H)-ones. The reaction proceeds diastereoselectively with the formation of trans-isomers and represents a cascade process involving the Knoevenagel condensation, the carbo-Michael reaction, and intramolecular nucleophilic substitution.

A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin

The clonidine-like central antihypertensive agent rilmenidine, which has high affinity for I1-type imidazoline receptors (I1-IR) was recently found to have cytotoxic effects on cultured cancer cell lines. However, due to its pharmacological effects resulting also from α2-adrenoceptor activation, rilmenidine cannot be considered a suitable anticancer drug candidate. Here, we report the identification of novel rilmenidine-derived compounds with anticancer potential and devoid of α2-adrenoceptor effects by means of ligand- and structure-based drug design approaches. Starting from a large virtual library, eleven compounds were selected, synthesized and submitted to biological evaluation. The most active compound 5 exhibited a cytotoxic profile similar to that of rilmenidine, but without appreciable affinity to α2-adrenoceptors. In addition, compound 5 significantly enhanced the apoptotic response to doxorubicin, and may thus represent an important tool for the development of better adjuvant chemotherapeutic strategies for doxorubicin-insensitive cancers.

Identification of potential antileishmanial 1,3-disubstituted-4-hydroxy-6-methylpyridin-2(1H)-ones, in vitro metabolic stability, cytotoxicity and molecular modeling studies

We report the synthesis and in vitro evaluation of 1,3-disubstituted-4-hydroxy-6-methylpyridin-2(1H)-one derivatives against Leishmania donovani. Amongst the compound library synthesized, molecules 3d, 3f, 3h, 3i, 3l, and 3m demonstrated substantial dose-dependent killing of the promastigotes. Their IC50 values range from 55.0 to 77.0 μg/ml, with 3m (IC50 55.75 μg/ml) being equipotent with amphotericin B (IC50 50.0 μg/ml, used as standard). The most active compound 3m, is metabolically stable in rat liver microsomes. Furthermore, the molecules are highly specific against leishmania as shown by their weak antibacterial and antifungal activity. In vitro cytotoxicity studies show the compounds lack any cytotoxicity. Furthermore, molecular modeling studies show plausibility of binding to Leishmania donovani topoisomerase 1 (LdTop1). Structure activity relationships reveal bulky substitutions on the pyridone nitrogen are well-tolerated, and such compounds have better binding affinity. Intramolecular hydrogen bonds confer some rigidity to the molecules, rendering a degree of planarity akin to topotecan. Taken together, we emphasis the merits of molecules possessing the 1,3-disubstituted-4-hydroxy-6-methylpyridin-2(1H)-one skeleton as potential antileishmanial agents warranting further investigation.

Design, Synthesis, and Phenotypic Profiling of Pyrano-Furo-Pyridone Pseudo Natural Products

Natural products (NPs) inspire the design and synthesis of novel biologically relevant chemical matter, for instance through biology-oriented synthesis (BIOS). However, BIOS is limited by the partial coverage of NP-like chemical space by the guiding NPs. The design and synthesis of “pseudo NPs” overcomes these limitations by combining NP-inspired strategies with fragment-based compound design through de novo combination of NP-derived fragments to unprecedented compound classes not accessible through biosynthesis. We describe the development and biological evaluation of pyrano-furo-pyridone (PFP) pseudo NPs, which combine pyridone- and dihydropyran NP fragments in three isomeric arrangements. Cheminformatic analysis indicates that the PFPs reside in an area of NP-like chemical space not covered by existing NPs but rather by drugs and related compounds. Phenotypic profiling in a target-agnostic “cell painting” assay revealed that PFPs induce formation of reactive oxygen species and are structurally novel inhibitors of mitochondrial complex I.

4-hydroxy-2-pyridone derivatives and the δ-pyrone isostere as novel agents against Mycobacterium smegmatis biofilm inhibitors

Background: The treatment of a bacterial infection when the bacterium is growing in a biofilm is a vexed issue. This is because the bacteria in a biofilm behaves differently compared to the individual planktonic free-form. As a result, traditional antibacterial agents lose their activity. Objective: Presently, there are not many drugs that are effective against bacteria growing in biofilms. Based on literature reports, we have sought to develop novel derivatives of 4-hydroxy-2- pyridone as both antimycobacterial and antibiofilm agents. Methods: The pyridone derivatives were synthesized by reacting 4-hydroxy-6-methyl-2H-pyran-2- one with appropriate amines and followed by reaction with substituted phenyl isocyanates as reported in the literature. Results: Four compounds in this series significantly inhibit the growth and formation of biofilm by Mycobacterium smegmatis (mc2 155 strain) at 50 μg/ml. Further, in silico evaluation of the ADME parameters shows that these compounds possess good drug-like properties and have the potential to be developed both as antibiofilm and as oral antimycobacterial agents. Conclusion: This finding is of significance as presently very few small molecules are known to inhibit biofilm formation in mycobacteria. These compounds are unique in the sense that they are more potent against Mycobacterium smegmatis in the biofilm state compared to the planktonic form.

One-pot Two-step Reaction for Synthesis of Poly-substituted Pyrano[3,2-c]pyridones and Spiro[indoline-3,4′-pyrano[3,2-c]pyridine]-2,5′(6′H)-diones in Water

An efficient four-component approach for the synthesis poly-substituted pyrano[3,2-c]pyridones and spiro[indoline-3,4′-pyrano[3,2-c]pyridine]-2,5′(6′H)-diones in water has been established. During the reaction, the products were readily achieved through one-pot two-step reaction using solid acid as catalyst. The advantages of atom and step economy, the recyclability of heterogeneous solid acid catalyst, easy workup procedure, and the wide scope of substrates make the reaction a powerful tool for assembling pyrano[3,2-c]pyridone skeletons of chemical and medical interest.

Triacetic acid lactone as a common intermediate for the synthesis of 4-hydroxy-2-pyridones and 4-amino-2-pyrones

At ambient temperature, triacetic acid lactone reacts with amines to produce 4-amino-2-pyrones. If the temperature is raised to 100 °C, 4-hydroxy-2-pyridones are generated.

NOVEL 2-PYRIDONE DERIVATIVE AND PHARMACEUTICAL PRODUCT CONTAINING SAME

Disclosed is a novel 2-pyridone derivative represented by general formula (1), which has both angiotensin II receptor antagonist activity and PPAR-3 activating activity and is useful as a prophylactic and/or therapeutic agent for cardiovascular diseases and metabolic diseases. Also disclosed is a pharmaceutical composition which contains the novel 2-pyridone derivative. In general formula (1), R1 represents a C1-6 alkyl group or a C1-6 alkoxy group; R2 represents a C1-6 alkyl group or a C3-8 cycloalkyl group; R3 represents a C1-6 alkyl group, a C6-10 aryl-C1-6 alkyl group, a C1-6 alkoxy-C1-6 alkyl group or a group represented by formula (2) (wherein A represents a nitrogen atom or CH, and R5 represents a hydrogen atom or a C1-6 alkoxy group); and R4 represents a group represented by formula (3) or (4).

Synthesis of 6-substituted-4-hydroxy-2-pyridinones via intramolecular ketene trapping of functionalized enamine-dioxinones

The synthesis of various 6-substituted-4-hydroxy-2-pyridinones is reported. The functionalized keto-dioxinones were constructed via a diethylzinc mediated crossed Claisen condensation reaction and subsequent enamine formation, thermolysis, and cyclization

PYRIDINONE PYRAZOLE UREA AND PYRIMIDINONE PYRAZOLE UREA DERIVATIVES

This invention is directed generally to substituted pyridinone and pyrimidinone compounds that generally inhibit p38 kinase, TNF, and/or cyclooxygeπase activity. Such substituted pyridinone and pyrimidinone compounds include compounds generally corresponding in structure to the following formula: wherein Z, n, R1, R2a, R2b, R2c, R2d, R2e, R3a, R3b R3c, R3d, R4, R5, R6, R7a, R7b, R7c, R7d and R7e are as defined in this specification. This invention also is directed to compositions of such substituted pyridinones and pyrimidinones (particularly pharmaceutical compositions), and methods for treating disorders (typically pathological disorders) associated with p38 kinase activity, TNF activity, and/or cyclooxygenase-2 activity.