64197-01-9

Upstream product

• 98-98-6 2-Picolinic acid 
• 30766-03-1 4-bromo-2-picolinic acid 
• 22282-99-1 4-bromo-2-methylpyridine 

Downstream Products

• 29681-43-4 methyl 4-methoxypicolinate 
• 1209459-88-0 4-bromo-pyridine-2-carboxylic acid methyl amide 
• 1313738-91-8 N-methyl-4-( 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamide 
• 1431470-14-2 4-aminopyridine-2-carboxylic acid benzyl(tetrahydropyran-2-yloxy)amide 
• 1431470-13-1 4-azido-pyridine-2-carboxylic acid benzyl-(tetrahydro-pyran-2-yloxy)amide 
• 1431470-12-0 4-bromo-pyridine-2-carboxylic acid benzyl(tetrahydropyran-2-yloxy)amide 
• 1431470-11-9 4-bromopyridine-2-carboxylic acid benzylhydroxyamide 
• 1309921-15-0 4-bromo-N-(1-[2-chlorophenyl]-3-phenyl-1H-pyrazol-5-yl)picolinamide 
• 845779-06-8 2-(4-chlorobutyl)-1-(4-methoxybenzyl)-5,6-dihydropyridone-2-carboxylic acid methyl ester 
• 845779-13-7 5-iodo-1-(4-methoxybenzyl)-2-methyl-5,6-dihydropyridone-2-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Exploring the potential intracellular targets of vascular normalization based on active candidates

We previously developed two candidates with potency of inducing vascular normalization, BD7 and B14. However, the definite intracellular molecular target(s) responsible for their activity remains unknown. Herein, we report the discovery and functional assessment of several multifunctional photoaffinity probes for determining the potential biological targets of active compounds. The probes bear a photoaffinity moiety and a bioorthogonal unit attached to B7 or B14 and maintained the bioactivity of the parent active molecules. Using in vitro biological assays, we preliminarily identified VEGFR-2 as a potential intracellular target for the active candidates. Our results demonstrate the utility of these multifunctional photoaffinity probes for analyzing the biological activity and subcellular localization of the intracellular target proteins of active candidates.

SPIROCYCLIC COMPOUNDS

Disclosed herein are spirocyclic compounds, together with pharmaceutical compositions and methods of ameliorating and/or treating a cancer described herein with one or more of the compounds described herein.

Discovery of novel Ponatinib analogues for reducing KDR activity as potent FGFRs inhibitors

FGF receptors (FGFRs) are tyrosine kinases that are overexpressed in diverse tumors by genetic alterations such as gene amplifications, somatic mutations and translocations. Owing to this characteristic, FGFRs are attractive targets for cancer treatment. It has been demonstrated that most multi-targeted, ATP competitive tyrosine kinase inhibitors are active against FGFRs as well as other kinases. The design of new and more selective inhibitors of FGFRs, which might be reduced off-target and side effects, is a difficult yet significant challenge. The results of the current investigation, show that novel Ponatinib analogues are highly active as FGFR inhibitors and that they possess reduced kinase insert domain receptor (KDR) activities. Observations made in a structure and activity relationship (SAR) investigation led to the development of a promising, orally available lead compound 4, which displays a 50–100 fold in vitro selectivity for inhibition of FGFR1-3 over KDR. In addition, biological evaluation of compound 4 showed that it displays significant antitumor activities in FGFR1-amplificated H1581 and FGFR2-amplificated SNU-16 xenograft models.

Discovery of biphenyl-aryl ureas as novel VEGFR-2 inhibitors. Part 4: Exploration of diverse hinge-binding fragments

Abstract VEGFR-2 plays an essential role in angiogenesis and is an important target for cancer therapy. A series of biphenyl-aryl ureas were synthesized and evaluated as novel VEGFR-2 inhibitors. The pyridine, methylamine carbonyl pyridine and pivaloyl amide pyridine were introduced as novel hinge binding fragment. The majority of title compounds displayed potent VEGFR-2 inhibition. In particular, L1, L9, W14 and W15 exhibited significant enzymatic inhibitory activity with IC50 values of 0.36 nM, 0.22 nM, 0.15 nM and 0.14 nM. Compounds L1, L9 and W15 displayed potent antiproliferative activity against A549 and SMMC-7721 cells. SAR study suggested that incorporation of 3-trifluoromethyl and methylamine carbonyl on terminal pyridine could improve VEGFR-2 inhibitory activity. Molecular docking illustrated that urea moiety formed two critical hydrogen bonds with the DFG residues of VEGFR-2. The results indicated that these biphenyl-aryl ureas could serve as promising lead compounds for further optimization.

Rhodium(III)-catalyzed oxidative olefination of picolinamides: Convenient synthesis of 3-alkenylpicolinamides

A rhodium(III)-catalyzed selective olefination of picolinamide derivatives has been developed. The reaction shows high regioselectivity, low catalyst loading (0.5 mol%), high yield and good functional group tolerance, providing a convenient strategy for the synthesis of 3-alkenylpicolinamides.

Pyrimidin-4-one derivatives and their use in the treatment, amelioration or prevention of a viral disease

The present invention relates to a compound having the general formula II, optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, prodrug, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which is useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.

Dynamic combinatorial chemistry employing boronic acids/boronate esters leads to potent oxygenase inhibitors

Dynamic duo: The reversible reaction of boronic acids with alcohols to form boronate esters, coupled to protein mass spectrometry analyses, was used to discover potent oxygenase inhibitors. This dynamic combinatorial mass spectrometry technique could potentially be applied to the identification of other protein inhibitors. Copyright

Novel tetrahydropyrido[1,2-a]isoindolone derivatives (valmerins): Potent cyclin-dependent kinase/glycogen synthase kinase 3 inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts

The development of CDK and GSK3 inhibitors has been regarded as a potential therapeutic approach, and a substantial number of diverse structures have been reported to inhibit CDKs and GSK-3β in recent years. Only a few molecules have gone through or are currently undergoing clinical trials as CDK and GSK inhibitors. In this paper, we prepared valmerins, a new family containing the tetrahydropyrido[1,2-a]isoindone core. The fused heterocycle was prepared with a straightforward synthesis that was functionalized by a (het)arylurea. Twelve valmerins inhibited the CDK5 and GSK3 with an IC50 100 nM. A semiquantitative kinase scoring was realized, and a cellular screening was done. At the end of our study, we investigated the in vivo potency of one valmerin. Mice exhibited good tolerance to our lead, which proved its efficacy and clearly blocked tumor growth. Valmerins appear also as good candidates for further development as anticancer agents.

Design and synthesis of substituted N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamides as positive allosteric modulators of the metabotropic glutamate receptor subtype 5

Based on SAR in the alkyne class of mGlu5 receptor negative allosteric modulators and a set of amide-based positive allosteric modulators, optimized substitution of the aryl bring was used to create substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides.

Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists

A series of heterobiaryl amides was designed and synthesized as novel mGluR5 antagonists. The synthesis using palladium catalyzed Suzuki-Miyaura cross-coupling reactions provided an array of compounds with a range of in vitro activities. In particular, compound 9e, 4(3,5-difluorophenyl)-N-(6-methylpyridin-1-yl)picolinamide, exhibited nanomolar affinity at the mGluR5 and will serve as a template for future drug design.