Category: 56622-54-9

Dong, Guoqiang; Chen, Wei; Wang, Xia; Yang, Xinglin; Xu, Tianying; Wang, Pei; Zhang, Wannian; Rao, Yu; Miao, Chaoyu; Sheng, Chunquan published the artcile< Small Molecule Inhibitors Simultaneously Targeting Cancer Metabolism and Epigenetics: Discovery of Novel Nicotinamide Phosphoribosyltransferase (NAMPT) and Histone Deacetylase (HDAC) Dual Inhibitors>, Synthetic Route of 56622-54-9, the main research area is preparation NAMPT HDAC dual inhibitor cancer; antitumor preparation nicotinamide phosphoribosyltransferase histone deacetylase inhibitor.

Cancer metabolism and epigenetics are among the most intensely pursued research areas in anticancer drug discovery. Here we report the first small mols. that simultaneously inhibit nicotinamide phosphoribosyltransferase (NAMPT)and histone deacetylase (HDAC), two important targets of cancer metabolism and epigenetics, resp. Through iterative structure-based drug design, chem. synthesis, and biol. assays, a highly potent dual NAMPT and HDAC inhibitor was successfully identified. Compound 35 possessed excellent and balanced activities against both NAMPT (IC50 = 31 nM) and HDAC1 (IC50 = 55 nM). It could effectively induce cell apoptosis and autophagy and ultimately led to cell death. Importantly, compound 35 showed excellent in vivo antitumor efficacy in the HCT116 xenograft model. This proof-of-concept study demonstrates the feasibility of discovering an inhibitor targeting cancer metabolism and epigenetics and provides an efficient strategy for multitarget antitumor drug discovery.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Synthetic Route of 56622-54-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ungwitayatorn, Jiraporn; Wiwat, Chanpen; Matayatsuk, Chutima; Pimthon, Jutarat; Piyaviriyakul, Suratsawadee published the artcile< Synthesis and HIV-1 reverse transcriptase inhibitory activity of non-nucleoside phthalimide derivatives>, Quality Control of 56622-54-9, the main research area is phthalimide nonnucleoside derivative preparation HIV1 reverse transcriptase inhibitory activity.

A new type of non-nucleoside HIV-1 reverse transcriptase inhibitor in the phthalimide series has been synthesized from either the reaction of N-carboethoxyphthalimide with amines or phthalimide with appropriate alkyl halides. The in vitro inhibitory activity of the synthesized compounds was studied by a radiometric assay at a concentration of 200 μg/mL using poly(rA)•oligo(dT) as a template-primer and methyl-[3H]dTTP as a substrate. The three most potent compounds, I-III, exhibited IC50 values of 60.90, 98.10 and 120.75 μg/mL, resp., lower than the IC50 of delavirdine (502.22 μg/mL, using poly(rA)•oligo(dT) as a template-primer and [3H]dTTP as a substrate).

Chinese Journal of Chemistry published new progress about Cyclic imides Role: PAC (Pharmacological Activity), SPN (Synthetic Preparation), BIOL (Biological Study), PREP (Preparation). 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Quality Control of 56622-54-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zheng, Ke; Iqbal, Sarah; Hernandez, Pamela; Park, HaJeung; LoGrasso, Philip V.; Feng, Yangbo published the artcile< Design and Synthesis of Highly Potent and Isoform Selective JNK3 Inhibitors: SAR Studies on Aminopyrazole Derivatives>, Electric Literature of 56622-54-9, the main research area is aminopyrazole JNK3 enzyme inhibitor preparation structure neurodegeneration.

The c-jun N-terminal kinase 3 (JNK3) is expressed primarily in the brain. Numerous reports have shown that inhibition of JNK3 is a promising strategy for treatment of neurodegeneration. The optimization of aminopyrazole-based JNK3 inhibitors with improved potency, isoform selectivity, and pharmacol. properties by structure-activity relationship (SAR) studies utilizing biochem. and cell-based assays, and structure-based drug design is reported. These inhibitors had high selectivity over JNK1 and p38α, minimal cytotoxicity, potent inhibition of 6-OHDA-induced mitochondrial membrane potential dissipation and ROS generation, and good drug metabolism and pharmacokinetic (DMPK) properties for iv dosing. 26n was profiled against 464 kinases and was found to be highly selective hitting only seven kinases with >80% inhibition at 10 μM. Moreover, 26n showed good solubility, good brain penetration, and good DMPK properties. Finally, the crystal structure of 26k in complex with JNK3 was solved at 1.8 Å to explore the binding mode of aminopyrazole based JNK3 inhibitors.

Journal of Medicinal Chemistry published new progress about Drug metabolism. 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Electric Literature of 56622-54-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Hu, Ziwei; Banothu, Janardhan; Beesu, Mallesh; Gustafson, Collin J.; Brush, Michael J. H.; Trautman, Kathryn L.; Salyer, Alex C. D.; Pathakumari, Balaji; David, Sunil A. published the artcile< Identification of Human Toll-like Receptor 2-Agonistic Activity in Dihydropyridine-Quinolone Carboxamides>, Computed Properties of 56622-54-9, the main research area is dihydropyridine quinolone carboxamide synthesis SAR TLR2 vaccine adjuvant.

Using a multiplexed, reporter gene-based, high-throughput screen, we identified 9-fluoro-7-hydroxy-3-methyl-5-oxo-N-(pyridin-3-ylmethyl)-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxamide as a TLR2 agonist. Preliminary structure-activity relationship studies on the carboxamide moiety led to the identification of analogs that induce chemokines and cytokines in a TLR2-dependent manner. These results represent new leads for the development of vaccine adjuvants.

ACS Medicinal Chemistry Letters published new progress about Chemokines Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Computed Properties of 56622-54-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Liu, Mao-Chin; Lin, Tai-Shun; Cory, Joseph G.; Cory, Ann H.; Sartorelli, Alan C. published the artcile< Synthesis and Biological Activity of 3- and 5-Amino Derivatives of 2-Pyridinecarboxaldehyde Thiosemicarbazone>, Computed Properties of 56622-54-9, the main research area is Hydrazinecarbothioamide pyridinylmethylene preparation ribonucleoside diphosphate reductase; pyridinecarboxaldehyde thiosemicarbazone preparation ribonucleoside diphosphate reductase; CDP reductase pyridinecarboxaldehyde thiosemicarbazone preparation.

A series of 3- and 5-alkylamino derivatives, as well as other structurally modified analogs of 2-pyridinecarboxaldehyde thiosemicarbazone, were synthesized and evaluated as inhibitors of CDP reductase activity and for their cytotoxicity in vitro and antineoplastic activity in vivo against the L1210 leukemia. Examples of the target compounds were the pyridinecarboxaldehyde thiosemicarbazones I (R = alkyl, allyl). The most biol. active compounds were I (R = Me, Et, allyl), which were potent inhibitors of ribonucleotide reductase with corresponding IC50 values of 1.3, 1.0, and 1.4 μM. The latter compounds produced a significant prolongation of the survival time of L1210 leukemia-bearing mice, with corresponding optimum % T/C values of 223, 204, and 215 when administered twice daily for six consecutive days at dosages of 60, 80, and 80 mg/kg, resp.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Computed Properties of 56622-54-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Firth, Nicholas C.; Atrash, Butrus; Brown, Nathan; Blagg, Julian published the artcile< MOARF, an Integrated Workflow for Multiobjective Optimization: Implementation, Synthesis, and Biological Evaluation>, Safety of (6-Methylpyridin-3-yl)methanamine, the main research area is MOARF structure activity relationship.

We describe the development and application of an integrated, multiobjective optimization workflow (MOARF) for directed medicinal chem. design. This workflow couples a rule-based mol. fragmentation scheme (SynDiR) with a pharmacophore fingerprint-based fragment replacement algorithm (RATS) to broaden the scope of reconnection options considered in the generation of potential solution structures. Solutions are ranked by a multiobjective scoring algorithm comprising ligand-based (shape similarity) biochem. activity predictions as well as physicochem. property calculations Application of this iterative workflow to optimization of the CDK2 inhibitor Seliciclib (CYC202, R-roscovitine) generated solution mols. in desired physicochem. property space. Synthesis and exptl. evaluation of optimal solution mols. demonstrates CDK2 biochem. activity and improved human metabolic stability.

Journal of Chemical Information and Modeling published new progress about Drug design. 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Safety of (6-Methylpyridin-3-yl)methanamine.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Huang, Chia-Yu; Stauffer, Tara M.; Strickland, Corey L.; Reader, John C.; Huang, He; Li, Ge; Cooper, Alan B.; Doll, Ronald J.; Ganguly, Ashit K.; Baldwin, John J.; Rokosz, Laura L. published the artcile< Guiding farnesyltransferase inhibitors from an ECLiPS library to the catalytic zinc>, Formula: C7H10N2, the main research area is piperazine derivative preparation structure farnesyltransferase inhibitor crystal structure.

Farnesyltransferase inhibitors identified from an ECLiPS library were optimized using solution-phase synthesis. X-ray crystallog. of inhibited complexes was used to identify substructures that coordinate to the active site zinc. The x-ray structures were ultimately used to guide the design of second-generation analogs with FTase IC50s of less than 1.0 nM.

Bioorganic & Medicinal Chemistry Letters published new progress about Conformation. 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Formula: C7H10N2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zheng, Ke; Iqbal, Sarah; Hernandez, Pamela; Park, HaJeung; LoGrasso, Philip V.; Feng, Yangbo published the artcile< Correction to Design and Synthesis of Highly Potent and Isoform Selective JNK3 Inhibitors: SAR Studies on Aminopyrazole Derivatives [Erratum to document cited in CA162:029776]>, Product Details of C7H10N2, the main research area is aminopyrazole JNK3 enzyme inhibitor preparation structure neurodegeneration erratum.

On page S4, Section 2.1, Line 1 of the supporting Inforamtion is incorrect; The correct information is given.

Journal of Medicinal Chemistry published new progress about Drug metabolism. 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Product Details of C7H10N2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Meng, Genyi; Guo, Taijie; Ma, Tiancheng; Zhang, Jiong; Shen, Yucheng; Sharpless, Karl Barry; Dong, Jiajia published the artcile< Modular click chemistry libraries for functional screens using a diazotizing reagent>, Computed Properties of 56622-54-9, the main research area is alkyl aryl azide triazole chemoselective preparation; fluorosulfonyl azide generation chemoselective diazotization primary amine; combinatorial generation library alkyl aryl azide cycloaddition alkyne; functional screen click chem azide generated in situ.

Alkyl and aryl azides were prepared from the corresponding primary alkyl and aryl amines by reaction with fluorosulfonyl azide generated in situ from a fluorosulfonylimidazolium triflate and sodium azide, expanding access to azides and both to the 1,2,3-triazoles derived from them and to functional screens employing them. The method allowed the preparation of a library of >1000 azides from the corresponding amines; the azide library underwent copper-catalyzed azide-alkyne cycloaddition reactions to yield a library of >1000 1,2,3-triazoles.

Nature (London, United Kingdom) published new progress about Alkyl azides Role: CMB (Combinatorial Study), RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Computed Properties of 56622-54-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kalindjian, S. Barret; Kadnur, Sanjay V.; Hewson, Christopher A.; Venkateshappa, Chandregowda; Juluri, Suresh; Kristam, Rajendra; Kulkarni, Bheemashankar; Mohammed, Zainuddin; Saxena, Rohit; Viswanadhan, Vellarkad N.; Aiyar, Jayashree; McVey, Donna published the artcile< A New Series of Orally Bioavailable Chemokine Receptor 9 (CCR9) Antagonists; Possible Agents for the Treatment of Inflammatory Bowel Disease>, Quality Control of 56622-54-9, the main research area is dioxoisoindoline derivative preparation CCR9 antagonist inflammatory bowel disease pharmacokinetics.

Chemokine receptor 9 (CCR9), a cell surface chemokine receptor which belongs to the G protein-coupled receptor, 7-trans-membrane superfamily, is expressed on lymphocytes in the circulation and is the key chemokine receptor that enables these cells to target the intestine. It has been proposed that CCR9 antagonism represents a means to prevent the aberrant immune response of inflammatory bowel disease in a localized and disease specific manner and one which is accessible to small mol. approaches. One possible reason why clin. studies with vercirnon, a prototype CCR9 antagonist, were not successful may be due to a relatively poor pharmacokinetic (PK) profile for the mol. We wish to describe work aimed at producing new, orally active CCR9 antagonists based on the 1,3-dioxoisoindoline skeleton. This study led to a number of compounds that were potent in the nanomolar range and which, on optimization, resulted in several possible preclin. development candidates with excellent PK properties.

Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Quality Control of 56622-54-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem