2682-86-2

Upstream product

• 3099-31-8 nicotinyl chloride 
• 2870-30-6 sodium diethyl phosphate 
• 762-04-9 phosphonic acid diethyl ester 

Downstream Products

• 129078-91-7 <(1-benzylpyridino)-3-methyl>phosphonic acid 
• 1415818-78-8 C₁₉H₂₇N₂O₄P 
• 74095-34-4 (3-Pyridylmethyl)phosphonic Acid 

Relevant academic research and scientific papers

Antimalarial and structural studies of pyridine-containing inhibitors of 1-deoxyxylulose-5-phosphate reductoisomerase

1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) in the nonmevalonate isoprene biosynthesis pathway is a target for developing antimalarial drugs. Fosmidomycin, a potent DXR inhibitor, showed safety as well as efficacy against Plasmodium falciparum malaria in clinical trials. On the basis of our previous quantitative structure-activity relationship (QSAR) and crystallographic studies, several novel pyridine-containing fosmidomycin derivatives were designed, synthesized, and found to be highly potent inhibitors of P. falciparum DXR (PfDXR) having Ki values of 1.9-13 nM, with the best one being ～11× more active than fosmidomycin. These compounds also potently block the proliferation of multidrug resistant P. falciparum with EC 50 values as low as 170 nM. A 2.3 A? crystal structure of PfDXR in complex with one of the inhibitors is reported, showing that the flexible loop of the protein undergoes conformational changes upon ligand binding and a hydrogen bond and favorable hydrophobic interactions between the pyridine group and the PfDXR account for the enhanced activity.

The discovery of PLK4 inhibitors: (E)-3-((1H-indazol-6-yl)methylene) indolin-2-ones as novel antiproliferative agents

The family of Polo-like kinases is important in the regulation of mitotic progression; this work keys on one member, namely Polo-like kinase 4 (PLK4). PLK4 has been identified as a candidate anticancer target which prompted a search for potent and selective inhibitors of PLK4. The body of the paper describes lead generation and optimization work which yielded nanomolar PLK4 inhibitors. Lead generation began with directed virtual screening, using a ligand-based focused library and a PLK4 homology model. Validated hits were used as starting points for the design and discovery of PLK4 inhibitors of novel structure, namely (E)-3-((1H-indazol-6-yl)methylene)indolin-2-ones. Computational models, based on a published X-ray structure (PLK4 kinase domain), were used to understand and optimize the in vitro activity of the series; potent antiproliferative activity was obtained. The kinase selectivity profile and cell cycle analysis of selected inhibitors are described. The results of a xenograft study with an optimized compound 50 (designated CFI-400437) support the potential of these novel PLK4 inhibitors for cancer therapy.

INDAZOLYL, BENZIMIDAZOLYL, BENZOTRIAZOLYL SUBSTITUTED INDOLMONE DERIVATIVES AS KINASE INHIBITORS USEFUL IN THE TREATMENT OF CANCER

The present invention is directed to a compound is represented by Structural Formula (A):or a pharmaceutically acceptable salt therof. The present invention is also directed to a pharmaceutical composition comprising a compound represented by Structural Formula (A) described above or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a subject having cancer, wherein the method comprises administering a therapeutically effective amount of a compound represented by Structural Formula (A) described above or a pharmaceutically acceptable salt thereof.

[(SUBSTITUTED) PHENYALKYL]FURYLALKYNYL-AND [SUBSTITUTED)PHENYALKYL]THIENYLALKYNYL-N-HYDROXYUREA INHIBITORS OR LEUKOTRIENE BIOSYNTHESIS

The present invention relates to compounds of the formula and the pharmaceutically acceptable salts thereof wherein Z is selected from optionally substituted phenyl, furyl, thienyl or thiazolyl; which inhibits leukotriene biosynthesis and is useful in the treatment of inflammatory disease states; also disclosed are leukotriene biosynthesis inhibiting compositions and a method for inhibiting 5-lipoxygenase activity and leukotriene biosynthesis

PHOTODEPHOSPHORYLATION OF PHOSPHONIC ACIDS

Photolysis of phosphonic acids in an alkaline aqeous solution gave 1-benzyl-methylpyridinium phosphates by the photocleavage of the C-P bond.

Photolysis of Pyridylmethyl- and Pyridiniomethylphosphonic Acids

Upon UV-irradiation, the C-P bond of (4-pyridylmethyl)phosphonic acid cleaved only near the isoelectronic point to give 4-methylpyridinium phophate, while (1-benzyl-4-pyridiniomethyl)phosphonic acid underwent C-P bond cleavage above pH 4 to give 1-benzyl-4-methylpyridinium phosphate.On the other hand, the C-P bond of (2-pyridylmethyl)phosphonic acid cleaved under pH region of about 1 to 2, while (1-benzyl-2-pyridiniomethyl)phosphonic acid underwent C-P bond cleavage above pH4.