80056-43-5

Upstream product

• 142-08-5 2-Pyridone 
• 623-73-4 diazoacetic acid ethyl ester 
• 105-36-2 ethyl bromoacetate 
• 142-08-5 2-hydroxypyridin 
• 109-09-1 2-chloropyridine 
• 40864-08-2 2-benzyloxypyridine 

Downstream Products

• 56546-36-2 (2-oxo-2H-pyridin-1-yl)-acetic acid 
• 1159992-89-8 ethyl (2Z)-2-(2-oxo-1,2-dihydropyridin-1-yl)-3-phenylprop-2-enoate 
• 27329-06-2 (2Z)-2-(2-oxo-1,2-dihydropyridin-1-yl)-3-phenylprop-2-enoic acid 
• 140870-17-3 N-phenyl-4-amino-3-ethoxycarbonyl-5-methoxycarbonyl-2-azatricyclo<5.2.2.0^2,6>undec-3,5,8-triene-10,11-exo-dicarboximide 
• 140870-16-2 N-phenyl-3-<(Z)-cyano((E)-methoxycarbonyl)>-2-ethoxycarbonylmethyl-2-azabicyclo<2.2.2>oct-7-ene-5,6-endo-dicarboximide 
• 121876-67-3 N-phenyl-4-amino-5-cyano-3-ethoxycarbonyl-2-azatricyclo<5.2.2.0^2,6>undec-3,5,8-triene-10,11-exo-dicarboximide 
• 121876-63-9 N-phenyl-2-ethoxycarbonylmethyl-3-dicyanomethylene-2-azabicyclo<2.2.2>oct-7-ene-5,6-endo-dicarboximide 

Relevant academic research and scientific papers

Route exploration and synthesis of the reported pyridone-based PDI inhibitor STK076545

The enzyme protein disulfide isomerase (PDI) is essential for the correct folding of proteins and the activation of certain cell surface receptors, and is a promising target for the treatment of cancer and thrombotic conditions. A previous high-throughput screen identified the commercial compound STK076545 as a promising PDI inhibitor. To confirm its activity and support further biological studies, a resynthesis was pursued of the reported β-keto-amide with an N-alkylated pyridone at the α-position. Numerous conventional approaches were complicated by undesired fragmentations or rearrangements. However, a successful 5-step synthetic route was achieved using an aldol reaction with an α-pyridone allyl ester as a key step. An X-ray crystal structure of the final compound confirmed that the reported structure of STK076545 was achieved, however its lack of PDI activity and inconsistent spectral data suggest that the commercial structure was misassigned.

Metal-free regioselective direct thiolation of 2-pyridones

A highly regioselective metal-free direct C-H thiolation of 2-pyridones with disulfides or thiols has been developed. A combination of persulfate and a commercially available halide source such as LiCl, NCS or I2 enables the successful direct incorporation of a sulfide moiety into the 5-position of pyridone under mild conditions, providing a useful and convenient approach for the preparation of a diverse array of 5-thio-substituted pyridones in moderate to excellent yields.

Nitrogen heterocyclic ring group substituted amide derivative and application thereof

The invention discloses a nitrogen heterocyclic ring group substituted amide derivative and application thereof, particularly relates to a novel nitrogen heterocyclic ring group substituted amide derivative and a drug composition comprising the compound, and further relates to methods for preparing the compound and the drug composition, and application of the compound and the drug composition to preparation of drugs for treating diseases or symptoms, particularly overactive bladder, excited and mediated by beta 3-adrenergic receptors. The compound and the drug composition can be used for activating the beta 3-adrenergic receptors.

Development of novel amides as noncovalent inhibitors of immunoproteasomes

The development of immunoproteasome-selective inhibitors is a promising strategy for treating hematologic malignancies, autoimmune and inflammatory diseases. In this context, we report the design, synthesis, and biological evaluation of a new series of amide derivatives as immunoproteasome inhibitors. Notably, the designed compounds act as noncovalent inhibitors, which might be a promising therapeutic option because of the lack of drawbacks and side effects associated with irreversible inhibition. Among the synthesized compounds, we identified a panel of active inhibitors with Ki values in the low micromolar or sub-micromolar ranges toward the b5i and/or b1i subunits of immunoproteasomes. One of the active compounds was shown to be the most potent and selective inhibi-tor with a Ki value of 21 nm against the single b1i subunit. Docking studies allowed us to determine the mode of binding of the molecules in the catalytic site of immunoproteasome subunits.

Development of peptidomimetic boronates as proteasome inhibitors

Proteasome inhibition has emerged over the past decade as an effective therapeutic approach for the treatment of hematologic malignancies. It is a multicatalytic complex, whose proteolytic activity relies in three types of subunits: chymotrypsin-like (β5), trypsin-like (β2) and caspase-like (β1). Most important for the development of effective antitumor agents is the inhibition of the β5 subunits. In this context, the dipeptide boronate bortezomib (Velcade) represents the first proteasome inhibitor approved by the FDA and the lead compound in drug discovery. This paper describes the synthesis and biological evaluation of a series of conformationally constrained pseudopeptide boronates (1-3) structurally related to bortezomib. The synthesized compounds showed a promising inhibitory profile by blocking primarily the chymotrypsin-like activity of the proteasome with Ki values in submicromolar/micromolar range. These compounds also resulted quite selective since no significant inhibition was recorded in the test against bovine pancreatic α-chymotrypsin. The obtained results were rationalized by means of docking experiments based on a model of the crystal structure of bortezomib bound to the yeast 20S proteasome providing essential insights for further optimization of this class of inhibitors.

Heterocyclic compounds as P2X7 ion channel blockers

The present invention relates to a novel series of 4,5-diphenyl-2-amino-4,5-dihydro-imidazole derivatives of the formula II: 1 wherein R, R1, R2, R3, R4, R5, X and Y are as defined herein. This invention also relates to methods of making these compounds. The compounds of this invention are P2X7 ion channel blockers and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases having an inflammatory component, including inflammatory bowel disease, rheumatoid arthritis and disease conditions associated with the central nervous system, such as stroke, Alzheimer''s disease, etc.

SUBSTITUTED VINYL PYRIDINE DERIVATIVE AND DRUGS CONTAINING THE SAME

The present invention relates to a substituted vinylpyridine derivative represented by the following formula (1): (wherein R1 represents a hydrogen atom, an alkyl group, etc., R2 represents an alkyl group; one of R3 and R4, which are different from each o

A SYNTHESIS OF A NEW TYPE HETEROCYCLIC COMPOUND USING DIELS-ALDER CYCLOADDITION OF 2-METHYLENE-1,2-DIHYDROPYRIDINES

Diels-Alder cycloaddition of 2-methylene-1,2-dihydropyridines having an active methylene group at the 1-position with N-phenylmaleimide gave isoquinuclidines, and cyclization of the adducts obtained afforded a new type of heterocyclic ring system, 2-azatricyclo2,6>undecanes.