Category: 16799-05-6

Huihui, Kierra M. M.; Shrestha, Ruja; Weix, Daniel J. published the artcile< Nickel-Catalyzed Reductive Conjugate Addition of Primary Alkyl Bromides to Enones To Form Silyl Enol Ethers>, Computed Properties of 16799-05-6, the main research area is reductive conjugate addition primary alkyl bromide enone nickel catalyst; silyl enol ether preparation.

Conjugate addition of organometallic reagents to enones to form silyl enol ether products is a versatile method to difunctionalize activated olefins, but the organometallic reagents required can be limiting. The reductive cross-electrophile coupling of unhindered primary alkyl bromides with enones and chlorosilanes to form silyl enol ether products is catalyzed by a nickel-complexed ortho-brominated terpyridine ligand. The conditions are compatible with a variety of cyclic/acyclic enones and functional groups.

Organic Letters published new progress about Bromoalkanes Role: RCT (Reactant), RACT (Reactant or Reagent). 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, Computed Properties of 16799-05-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Nguyen, Son T.; Kwasny, Steven M.; Ding, Xiaoyuan; Cardinale, Steven C.; McCarthy, Courtney T.; Kim, Hong-Suk; Nikaido, Hiroshi; Peet, Norton P.; Williams, John D.; Bowlin, Terry L.; Opperman, Timothy J. published the artcile< Structure-activity relationships of a novel pyranopyridine series of Gram-negative bacterial efflux pump inhibitors>, Formula: C8H8BrCl, the main research area is pyranopyridine antibacterial efflux pump inhibitor pharmacokinetics; Adjunctive therapy; Antibacterial; Efflux pump inhibitor; Enterobacteriaceae; Pyranopyridine.

Recently the authors described a novel pyranopyridine inhibitor (MBX2319) of RND-type efflux pumps of the Enterobacteriaceae. MBX2319 (3,3-dimethyl-5-cyano-8-morpholino-6-(phenethylthio)-3,4-dihydro-1H-pyrano[3,4-c]pyridine) is structurally distinct from other known Gram-neg. efflux pump inhibitors (EPIs), such as 1-(1-naphthylmethyl)-piperazine (NMP), phenylalanylarginine-β-naphthylamide (PAβN), D13-9001, and the pyridopyrimidine derivatives Here, the authors report the synthesis and biol. evaluation of 60 new analogs of MBX2319 that were designed to probe the structure activity relationships (SARs) of the pyranopyridine scaffold. The results of these studies produced a mol. activity map of the scaffold, which identifies regions that are critical to efflux inhibitory activities and those that can be modified to improve potency, metabolic stability and solubility Several compounds are significantly more effective than MBX2319 at potentiating the antibacterial activity of levofloxacin and piperacillin against Escherichia coli.

Bioorganic & Medicinal Chemistry published new progress about Antibacterial agents. 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, Formula: C8H8BrCl.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Zhou, Juan; Mock, Elliot D.; Al Ayed, Karol; Di, Xinyu; Kantae, Vasudev; Burggraaff, Lindsey; Stevens, Anna F.; Martella, Andrea; Mohr, Florian; Jiang, Ming; van der Wel, Tom; Wendel, Tiemen J.; Ofman, Tim P.; Tran, Yvonne; de Koster, Nicky; van Westen, Gerard J. P.; Hankemeier, Thomas; van der Stelt, Mario published the artcile< Structure-Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family>, HPLC of Formula: 16799-05-6, the main research area is PLAAT inhibitor NAPEs NAEs anandamide alpha ketoamides SAR.

The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists of five members, which are involved in the Ca2+-independent production of N-acylphosphatidylethanolamines (NAPEs). NAPEs are lipid precursors for bioactive N-acylethanolamines (NAEs) that are involved in various physiol. processes such as food intake, pain, inflammation, stress, and anxiety. Recently, we identified α-ketoamides as the first pan-active PLAAT inhibitor scaffold that reduced arachidonic acid levels in PLAAT3-overexpressing U2OS cells and in HepG2 cells. Here, we report the structure-activity relationships of the α-ketoamide series using activity-based protein profiling. This led to the identification of LEI-301(I), a nanomolar potent inhibitor for the PLAAT family members. LEI-301 reduced the NAE levels, including anandamide, in cells overexpressing PLAAT2 or PLAAT5. Collectively, LEI-301 may help to dissect the physiol. role of the PLAATs.

Journal of Medicinal Chemistry published new progress about N-Acylethanolamines Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, HPLC of Formula: 16799-05-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Han, Yong; Zheng, Bo; Peng, Yungui published the artcile< Construction of Chiral 2-Substituted Octahydroindoles from Cyclic Ketones and Nitroolefins Bearing only One α-Substituent>, COA of Formula: C8H8BrCl, the main research area is cyclic ketone nitroolefin amine phosphoric acid catalyst Michael addition; gamma nitro ketone preparation enantioselective intramol reductive amination; octahydroindole preparation.

A dual catalytic system was developed following the screening of a series of chiral primary amine catalysts and chiral phosphoric acid catalysts for the Michael addition of cyclic ketones to nitroolefins bearing only one α-substituent. The resulting γ-nitro ketones, which contain a substituent on the carbon connected to the nitro group, were formed in excellent yields (>80%) with high levels of stereoselectivity (up to 94:6 dr and 98% ee) when the reaction was performed in benzene at 0° with 10 mol% of the optimal amine/phosphoric acid combination (1:1) as a catalyst. Subsequent reduction of the nitro group followed by intramol. reductive amination afforded optically active cis-octahydroindole analogs bearing a non-functional substituent at their 2-position.

Advanced Synthesis & Catalysis published new progress about Alkenes, nitro Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, COA of Formula: C8H8BrCl.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Pau, Amedeo; Catto, Marco; Pinna, Giovanni; Frau, Simona; Murineddu, Gabriele; Asproni, Battistina; Curzu, Maria M.; Pisani, Leonardo; Leonetti, Francesco; Loza, Maria Isabel; Brea, Jose; Pinna, Gerard A.; Carotti, Angelo published the artcile< Multitarget-Directed Tricyclic Pyridazinones as G Protein-Coupled Receptor Ligands and Cholinesterase Inhibitors>, Application of C8H8BrCl, the main research area is tricyclic pyridazinone GPCR ligand cholinesterase inhibitor; AChE inhibitors; BChE inhibitors; GPCR ligands; multitarget-directed ligands; neurodegenerative diseases.

By following a multitarget ligand design approach, a library of 47 compounds was prepared, and they were tested as binders of selected G protein-coupled receptors (GPCRs) and inhibitors of acetyl and/or butyryl cholinesterase. The newly designed ligands feature pyridazinone-based tricyclic scaffolds connected through alkyl chains of variable length to proper amine moieties (e.g., substituted piperazines or piperidines) for GPCR and cholinesterase (ChE) mol. recognition. The compounds were tested at three different GPCRs, namely serotoninergic 5-HT1A, adrenergic α1A, and dopaminergic D2 receptors. Our main goal was the discovery of compounds that exhibit, in addition to ChE inhibition, antagonist activity at 5-HT1A because of its involvement in neuronal deficits typical of Alzheimer’s and other neurodegenerative diseases. Ligands with nanomolar affinity for the tested GPCRs were discovered, but most of them behaved as dual antagonists of α1A and 5-HT1A receptors. Nevertheless, several compounds displaying this GPCR affinity profile also showed moderate to good inhibition of AChE and BChE, thus deserving further investigations to exploit the therapeutic potential of such unusual biol. profiles.

ChemMedChem published new progress about 5-HT1A receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, Application of C8H8BrCl.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Wang, Bingbing; Peng, Pan; Ma, Wan; Liu, Zhao; Huang, Cheng; Cao, Yangmin; Hu, Ping; Qi, Xiaotian; Lu, Qingquan published the artcile< Electrochemical Borylation of Alkyl Halides: Fast, Scalable Access to Alkyl Boronic Esters>, Synthetic Route of 16799-05-6, the main research area is electrochem borylation alkyl halide reduction mechanism DFT; alkyl boronic ester preparation electrochem; mol structure optimized boronic ester alkyl halide DFT.

Herein, a fast, scalable, and transition-metal-free borylation of alkyl halides (X = I, Br, Cl) enabled by electroreduction is reported. This process provides an efficient and practical access to primary, secondary, and tertiary boronic esters at a high current. More than 70 examples, including the late-stage borylation of natural products and drug derivatives, are furnished at room temperature, thereby demonstrating the broad utility and functional-group tolerance of this protocol. Mechanistic studies disclosed that B2cat2 serves as both a reagent and a cathodic mediator, enabling electroreduction of difficult-to-reduce alkyl bromides or chlorides at a low potential.

Journal of the American Chemical Society published new progress about Bond cleavage. 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, Synthetic Route of 16799-05-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Matsuno, Kenji; Takai, Kazushige; Isaka, Yoshinobu; Unno, Yuka; Sato, Masayuki; Takikawa, Osamu; Asai, Akira published the artcile< S-Benzylisothiourea derivatives as small-molecule inhibitors of indoleamine-2,3-dioxygenase>, Category: chlorides-buliding-blocks, the main research area is benzylisothiourea derivative preparation indoleamine dioxygenase inhibitor.

S-Benzylisothiourea was discovered by its ability to inhibit indoleamine-2,3-dioxygenase (IDO) in our screening program. Subsequent optimization of the initial hit leads to the identification of sub-μM inhibitors of which suppressed kynurenine production in A431 cells. Synthesis and structure-activity relationship of S-benzylisothiourea analogs as small-mol. inhibitors of IDO are described.

Bioorganic & Medicinal Chemistry Letters published new progress about Enzyme inhibitors (indoleamine dioxygenase). 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, Category: chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Suzuki, Takayoshi; Ota, Yosuke; Ri, Masaki; Bando, Masashige; Gotoh, Aogu; Itoh, Yukihiro; Tsumoto, Hiroki; Tatum, Prima R.; Mizukami, Tamio; Nakagawa, Hidehiko; Iida, Shinsuke; Ueda, Ryuzo; Shirahige, Katsuhiko; Miyata, Naoki published the artcile< Rapid Discovery of Highly Potent and Selective Inhibitors of Histone Deacetylase 8 Using Click Chemistry to Generate Candidate Libraries>, Synthetic Route of 16799-05-6, the main research area is anticancer histone deacetylase 8 inhibitor preparation SAR.

To find HDAC8-selective inhibitors, we designed a library of HDAC inhibitor candidates, each containing a zinc-binding group that coordinates with the active-site zinc ion, linked via a triazole moiety to a capping structure that interacts with residues on the rim of the active site. These compounds were synthesized by using click chem. Screening identified HDAC8-selective inhibitors including (I) (IC50 = 0.070 μM), which was more potent than PCI-34058 (IC50 = 0.31 μM), a known HDAC8 inhibitor. Mol. modeling suggested that the phenylthiomethyl group of I binds to a unique hydrophobic pocket of HDAC8, and the orientation of the phenylthiomethyl and hydroxamate moieties (fixed by the triazole moiety) is important for the potency and selectivity. The inhibitors caused selective acetylation of cohesin in cells and exerted growth-inhibitory effects on T-cell lymphoma and neuroblastoma cells (GI50 = 3-80 μM). These findings suggest that HDAC8-selective inhibitors have potential as anticancer agents.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, Synthetic Route of 16799-05-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Miyagawa, Masayoshi; Akiyama, Toshiyuki; Mikamiyama-Iwata, Minako; Hattori, Kazunari; Kurihara, Naoko; Taoda, Yoshiyuki; Takahashi-Kageyama, Chika; Kurose, Noriyuki; Mikamiyama, Hidenori; Suzuki, Naoyuki; Takaya, Kenji; Tomita, Kenji; Matsuo, Kenji; Morimoto, Kenji; Yoshida, Ryu; Shishido, Takao; Yoshinaga, Tomokazu; Sato, Akihiko; Kawai, Makoto published the artcile< Discovery of novel 5-hydroxy-4-pyridone-3-carboxy acids as potent inhibitors of influenza Cap-dependent endonuclease>, HPLC of Formula: 16799-05-6, the main research area is hydroxy pyridonecarboxy acid preparation influenza Cap endonuclease inhibitor; Anti-influenza drug; Cap-dependent endonuclease; Chelator; Pyridone; Virtual modeling.

We report the discovery of a novel series of influenza Cap-dependent EndoNuclease (CEN) inhibitors based on the 4-pyridone-carboxylic acid (PYXA) scaffold, which were found from our chelate library. Our SAR research revealed the lipophilic domain to be the key to CEN inhibition. In particular, the position between the chelate and the lipophilic domain in the derivatives was essential for enhancing the potency. Our study, based on virtual modeling, led to the identification of 2y as a potent CEN inhibitor with an IC50 of 5.12 nM.

Bioorganic & Medicinal Chemistry Letters published new progress about Antiviral agents. 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, HPLC of Formula: 16799-05-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Rojas-Prats, Elisa; Martinez-Gonzalez, Loreto; Gonzalo-Consuegra, Claudia; Liachko, Nicole F.; Perez, Concepcion; Ramirez, David; Kraemer, Brian C.; Martin-Requero, Angeles; Perez, Daniel I.; Gil, Carmen; de Lago, Eva; Martinez, Ana published the artcile< Targeting nuclear protein TDP-43 by cell division cycle kinase 7 inhibitors: A new therapeutic approach for amyotrophic lateral sclerosis>, Synthetic Route of 16799-05-6, the main research area is cdc7 inhibitor TDP43 ALS FTLD drug discovery; ALS; CDC7 inhibitors; Drug discovery; FTLD; TDP-43.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no known cure. Aggregates of the nuclear protein TDP-43 have been recognized as a hallmark of proteinopathy in both familial and sporadic cases of ALS. Post-translational modifications of this protein, include hyperphosphorylation, cause disruption of TDP-43 homeostasis and as a consequence, promotion of its neurotoxicity. Among the kinases involved in these changes, cell division cycle kinase 7 (CDC7) plays an important role by directly phosphorylating TDP-43. In the present manuscript the discovery, synthesis, and optimization of a new family of selective and ATP-competitive CDC7 inhibitors based on 6-mercaptopurine scaffold are described. Moreover, we demonstrate the ability of these inhibitors to reduce TDP-43 phosphorylation in both cell cultures and transgenic animal models such as C. elegans and Prp-hTDP43 (A315T) mice. Altogether, the compounds described here may be useful as versatile tools to explore the role of CDC7 in TDP-43 phosphorylation and also as new drug candidates for the future development of ALS therapies.

European Journal of Medicinal Chemistry published new progress about Amyotrophic lateral sclerosis. 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, Synthetic Route of 16799-05-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics