Category: 387350-39-2

Liu, Ruiting; Tzounopoulos, Thanos; Wipf, Peter published the artcile< Synthesis and Optimization of Kv7 (KCNQ) Potassium Channel Agonists: The Role of Fluorines in Potency and Selectivity>, Formula: C7H7F3N2, the main research area is KCNQ potassium channel agonist preparation structure.

Based on the potent Kv7 agonist RL-81, we prepared new lead structures with greatly improved selectivity for Kv7.2/Kv7.3 over related potassium channels, i.e., Kv7.3/Kv7.5, Kv7.4, and Kv7.4/7.5. RL-36 and RL-12 maintain an agonist EC2x of ca. 1 μM on Kv7.2/Kv7.3 in a high-throughput assay on an automated electrophysiol. platform in HEK293 cells but lack activity on Kv7.3/Kv7.5, Kv7.4, and Kv7.4/7.5, resulting in a selectivity index SI > 10. RL-56 is remarkably potent, EC2x 0.11 ± 0.02 μM, and still shows an SI = 2.5. We also identified analogs with significant selectivity for Kv7.4/Kv7.5 over Kv7.2/Kv7.3. The extensive use of fluorine in iterative core structure modifications highlights the versatility of these substituents, including F, CF3, and SF5, to span orders of magnitude of potency and selectivity in medicinal chem. lead optimizations.

ACS Medicinal Chemistry Letters published new progress about Homo sapiens. 387350-39-2 belongs to class pyridine-derivatives, and the molecular formula is C7H7F3N2, Formula: C7H7F3N2.

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>, Formula: C7H7F3N2, 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). 387350-39-2 belongs to class pyridine-derivatives, and the molecular formula is C7H7F3N2, Formula: C7H7F3N2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Hai, Yang; Geng, Jia-Jia; Li, Peng-Jie; Ma, Wei-Ping; Wang, Cui-Fang; Wei, Mei-Yan; Hou, Xue-Mei; Chen, Guang-Ying; Gu, Yu-Cheng; Liu, Ming; Shao, Chang-Lun published the artcile< Semisynthesis and biological evaluation of (+)-sclerotiorin derivatives as antitumor agents for the treatment of hepatocellular carcinoma>, Recommanded Product: 3-(Aminomethyl)-6-(trifluoromethyl)pyridine, the main research area is hepatocellular cervical carcinoma sclerotiorin antitumor cytotoxicity pharmacokinetics signaling; (+)-Sclerotiorin; AKT and ERK proteins; Antitumor; Hepatocellular carcinoma; Mouse xenograft model.

Hepatocellular carcinoma is one of the most common primary hepatic malignancy. Herein, a series of semisynthesized derivatives (2-30) of the natural product (+)-sclerotiorin (1) was prepared and evaluated the cytotoxic activities against six cancer cell lines. Among them, 3 and 5 were the most effective compounds against human hepatocellular carcinoma Bel-7402 cell line with IC50 values of 1.45 and 1.15 μM, resp. Mol. mechanism study showed that 5 disrupted the mitochondrial membrane potential and induced apoptosis in a caspase-dependent manner. In addition, 5 affected AKT and ERK signaling pathways and induced AKT and ERK proteins degradation through ubiquitin-proteasome system. Furthermore, 5 displayed significant in vivo anticancer effects in the xenograft models with decreasing the tumor mass by 52.5%. The safety evaluation was confirmed by acute toxicity subchronic toxicity tests, paraffin sections of mice organ and blood routine examination Taken together, 5 can be developed as a potential therapeutic agent for hepatocellular carcinoma.

European Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 387350-39-2 belongs to class pyridine-derivatives, and the molecular formula is C7H7F3N2, Recommanded Product: 3-(Aminomethyl)-6-(trifluoromethyl)pyridine.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Basu, Sourav; Middya, Sandip; Banerjee, Monali; Ghosh, Rajib; Pryde, David C.; Yadav, Dharmendra B.; Shrivastava, Ritesh; Surya, Arjun published the artcile< The discovery of potent small molecule cyclic urea activators of STING>, Application In Synthesis of 387350-39-2, the main research area is cyclic urea preparation interferon stimulator activation; Immune oncology; Innate immunity; Interferon; STING; cGAS.

STING mediates innate immune responses that are triggered by the presence of cytosolic DNA. Activation of STING to boost antigen recognition is a therapeutic modality that is currently being tested in cancer patients using nucleic-acid based macrocyclic STING ligands. We describe here the discovery of 3,4-dihydroquinazolin-2(1H)-one based 6,6-bicyclic heterocyclic agonists of human STING that activate all known human variants of STING with high potency.

European Journal of Medicinal Chemistry published new progress about Heterocyclic compounds, nitrogen Role: PAC (Pharmacological Activity), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 387350-39-2 belongs to class pyridine-derivatives, and the molecular formula is C7H7F3N2, Application In Synthesis of 387350-39-2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Dharuman, Suresh; Wallace, Miranda J.; Reeve, Stephanie M.; Bulitta, Jurgen B.; Lee, Richard E. published the artcile< Synthesis and Structure-Activity Relationship of Thioacetamide-Triazoles against Escherichia coli>, Electric Literature of 387350-39-2, the main research area is thioacetamide triazole preparation SAR antibacterial; 1,2,3-triazoles; antibiotics; antimetabolite; gram-negative active compounds.

Infections due to Gram-neg. bacteria are increasingly dangerous due to the spread of multi-drug resistant strains, emphasizing the urgent need for new antibiotics with alternative modes of action. Authors have previously identified a novel class of antibacterial agents, thioacetamide-triazoles, using an antifolate targeted screen and determined their mode of action which is dependent on activation by cysteine synthase A. Herein, authors report a detailed examination of the anti-E. coli structure-activity relationship of the thioacetamide-triazoles. Analogs of the initial hit compounds were synthesized to study the contribution of the aryl, thioacetamide, and triazole sections. A clear structure-activity relationship was observed generating compounds with excellent inhibition values. Substitutions to the aryl ring were generally best tolerated, including the introduction of thiazole and pyridine heteroaryl systems. Substitutions to the central thioacetamide linker section were more nuanced; the introduction of a Me branch to the thioacetamide linker substantially decreased antibacterial activity, but the isomeric propionamide and N-benzamide systems retained activity. Changes to the triazole portion of the mol. dramatically decreased the antibacterial activity, further indicating that 1,2,3-triazole is critical for potency. From these studies, authors have identified new lead compounds with desirable in-vitro ADME properties and in-vivo pharmacokinetic properties.

Molecules published new progress about Acetamides Role: PAC (Pharmacological Activity), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses) (Thio). 387350-39-2 belongs to class pyridine-derivatives, and the molecular formula is C7H7F3N2, Electric Literature of 387350-39-2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Chitti, Surendar; Pulya, Sravani; Nandikolla, Adinarayana; Patel, Tarun Kumar; Karan Kumar, Banoth; Murugesan, Sankaranarayanan; Ghosh, Balaram; Sekhar, Kondapalli Venkata Gowri Chandra published the artcile< Design, synthesis and biological evaluation of 7-(5-((substituted - amino)-methyl)-thiophen-2-yl)-spiro-[chroman-2,4'-piperidin]-4-one hydrochloride analogues as anticancer agents>, Recommanded Product: 3-(Aminomethyl)-6-(trifluoromethyl)pyridine, the main research area is spiro chromanpiperidinone hydrochloride preparation antitumor SAR ADME; Anticancer; Apoptosis; Cytotoxicity; Spiro-[chroman–2,4′–piperidin]–4–one.

A series of thirty-one novel 7-(5-((amino)-methyl)-thiophen-2-yl)-spiro-[chroman-2,4′-piperidin]-4-one analogs I (R = isopropylamine, tert-butylamine, 3,3-dimethylbutylamine, etc.) have been designed and synthesized as their hydrochloride salts. Here, the anticancer potential and biol. results of low-mol.-weight bridgehead oxygen and nitrogen-containing spirochromanones on proliferation and apoptosis of the human breast cancer cell line (MCF-7) and murine melanoma (B16F10) is evaluated . The anticancer activity ranged from 2.9 to 35.0μM. The most potent compounds I (R = thiophen-2-yl methanamine, benzyl amine, and Me amine) were found to be less toxic against human embryonic kidney (HEK-293) cell lines. Compounds I (R = benzyl amine and Me amine) were found to be causing significant cytotoxicity through apoptotic cell death and also G2 phase arrest of cell cycle in B16F10 cells. In-silico ADME prediction studies of the titled compounds were found within the rules outlined, and these compounds may not face any pharmacokinetic associated issues in the mere future upon developmental stage. These conjugates may serve as a lead for the discovery of potential anticancer drug candidate with better therapeutic profile.

Bioorganic Chemistry published new progress about Antitumor agents. 387350-39-2 belongs to class pyridine-derivatives, and the molecular formula is C7H7F3N2, Recommanded Product: 3-(Aminomethyl)-6-(trifluoromethyl)pyridine.

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>, Application In Synthesis of 387350-39-2, 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). 387350-39-2 belongs to class pyridine-derivatives, and the molecular formula is C7H7F3N2, Application In Synthesis of 387350-39-2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem