A convenient halogenation of 2-arylimidazo[1,2-a]pyridines using sodium chloride/bromide/iodide as the halogen sources in the presence of K2S2O8 as an easy-to-handle oxidizing agent was developed. The present work offers an efficient and rapid access to 3-chloro-, 3-bromo- and 3-iodo-2-arylimida...

As the activation of phosphatidylinositol 3-kinase (PI3K) is associated with a wide variety of human malignancies, it is emerging as an attractive target for cancer treatment. In this study we synthesized a novel PI3Kα inhibitor, IPD-196 [ethyl 6-(5-(2,4-difluorophenylsulfonamido)pyridin-3-yl)i...

The pair NaBH4-TMEDA as hydride source and a palladium catalyst in THF prove to be an efficient system for the hydrodehalogenation of halogenated heterocycles with one or more heteroatoms. In general, Pd(OAc)2-PPh3 rapidly hydrodehalogenates reactive halo-heterocycles such as bromo-pyridines, -q...

We have previously reported the imidazo[1,2-a]pyridine derivative 4 as a novel p110α inhibitor; however, although 4 is a potent inhibitor of p110α enzymatic activity and tumor cell proliferation in vitro, it is unstable in solution and ineffective in vivo. To increase stability the pyrazole of...

Melanoma is an aggressive form of skin cancer and it is generally associated with poor prognosis in patients with late-stage disease. Due to the increasing occurrence of melanoma, there is a need for the development of novel therapies. A new series of diarylamide and diarylurea derivatives conta...

We present herein the discovery and development of novel and potent Nek2 inhibitors with distinctive in vitro and in vivo antitumor activity based on an imidazo[1,2-a]pyridine scaffold. Our studies identified a nonlinear SAR for activity against both Nek2 and cancer cells. Bioisostere and struct...

The bromodomain and extraterminal (BET) family of proteins play a crucial role in promoting gene expression of critical oncogenes. Novel BET bromodomain inhibitors with excellent potency, drug metabolism and pharmacokinetics (DMPK) properties were in strong need for development. We reported a se...

An efficient CuI catalyzed intramolecular Ullmann-type C−N coupling reaction is described here. Newly substituted 1H-benzo[4,5]imidazo[1,2-a]pyrrolo[3,4-c]pyridine-1,3,5(2H, 11H)-trione has been easily synthesized from ortho halogenated N-substituted pyrrolo[3,4-c]pyridine-1,3,6(5H)-triones in p...

Trimethylsilylation of the anomeric hydroxyl groups of tetra-O-benzyl and tetra-O-acetyl galactopyranoses was investigated. Stereoselective formation of β-trimethylsilyl glycoside (β-TMS glycoside) of benzyl protected compound was achieved using N-trimethylsilyl diethylamine. In the course of ...

5-Aminopenta-2,4-dienals, and specially their N,N-disubstituted derivatives (Zincke aldehydes), are known for more than a century but their chemistry has not been highly exploited until recently. They are the most frequently prepared via the ring opening of 1-(2,4-dinitrophenyl)pyridinium salts ...

The influence of pyrophosphate during modification of myosin by β-hydroxyethyl-2,4-dinitrophenyl disulphide (HEDD) was studied.Pyrophosphate influenced the inhibitory phase of the action of HEDD on myosin Ca2+-ATPase (ATP phosphohydrolase, EC 3.6.1.3), and protected the ability of myosin to for...

The ethyl 2-acetamido-2-deoxy-1-thio-α-d-xylofuranoside (1a) previously reported was further acetylated to the 3,5-diacetate (1b), and this was completely deacetylated by successive treatment with phosphorus pentasulfide and methanolic ammonia. After introduction of the N-(2,4-dinitrophenyl) gr...

Adenine derivatives having a p-nitrophenyl group at position 2, 8, or 9 were directly mutagenic towards Salmonella typhimurium strains TA98 and TA100, whereas N6-(p-nitrophenyl)adenine was not mutagenic. 2,9- And 8,9-bis-(p-nitrophenyl)adenines were also mutagenic, but N6,9-bis-(p-nitrophenyl)ad...

This study was designed to study the influence of Sacoglottis gabonensis stem bark extract on the metabolic and cytotoxic side effects of 2,4-dinitrophenyl hydrazine (2,4-DNPH) on the brain and blood using male weaning rats as the experimental model. This was after the effect of the bark extract...

A new functional macrocyclic ligand, 2,4-dinitrophenylcyclen (= 1-(2,4-dinitrophenyl)-1,4,7,10-tetraazacyclododecane), has been synthesized and isolated as its trihydrochloric acid salt (L·3HCl). The protonation constants (log Kn) for three secondary nitrogens of L were determined by potentiome...

SummaryTranscriptional induction of heat shock protein (HSP) genes is accompanied by dynamic changes in their 3D structure and spatial organization, yet the molecular basis for these phenomena remains unknown. Using chromosome conformation capture and single-cell imaging, we show that genes tran...

IntroductionThe 72 kDa heat shock protein, HSP72, located intracellularly provides cochlear cytoprotective and anti-inflammatory roles in the inner ear during stressful noise challenges. The expression of intracellular HSP72 (iHSP72) can be potentiated by alanyl-glutamine dipeptide supplementati...

Despite efforts to restore Atlantic sturgeon in European rivers, aquaculture techniques result in animals with high post-release mortality due to, among other reasons, their low tolerance to increasing water temperature. Marker genes to monitor heat stress are needed in order to identify heat-re...

Heat shock proteins (HSP or stress proteins) are intracellular molecules that participate in physiological cell metabolism and growth, although they are known to be involved in many stress conditions. Statins inhibit the action of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-C...

Although many of heat shock proteins (HSPs) are crucial in homeostasis due to their role in maintaining cellular proteostasis by the integration of two pivotal processes—folding and degradation, several decades of cancer proteomics suggest that HSPs may improve cancer establishment and progress...