Category: 660867-80-1

Obligacion, Jennifer V.; Semproni, Scott P.; Chirik, Paul J. published the artcile< Cobalt-Catalyzed C-H Borylation>, Recommanded Product: 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, the main research area is cobalt complex borylation hereocycle arene crystal structure.

A family of pincer-ligated cobalt complexes has been synthesized and are active for the catalytic C-H borylation of heterocycles and arenes. The cobalt catalysts operate with high activity and under mild conditions and do not require excess borane reagents. Up to 5000 turnovers for Me furan-2-carboxylate have been observed at ambient temperature with 0.02 mol % catalyst loadings. A catalytic cycle that relies on a cobalt(I)-(III) redox couple is proposed.

Journal of the American Chemical Society published new progress about Borylation catalysts. 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Recommanded Product: 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Liu, Wenwu; Wu, Limeng; Li, Deping; Huang, Yaoguang; Liu, Mingyue; Liu, Wenjie; Tian, Caizhi; Liu, Xin; Jiang, Xiaowen; Hu, Xiaolong; Gao, Xudong; Xu, Zihua; Lu, Hongyuan; Zhao, Qingchun published the artcile< Discovery of novel tacrine derivatives as potent antiproliferative agents with CDKs inhibitory property>, Name: 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, the main research area is human colon lung cancer CDK9 antiproliferative anticancer tacrine derivative; AChE; CDK2; CDK9; Cancer therapeutics; Tacrine.

Tacrine was the first approved drug by the FDA for the treatment of Alzheimer′s disease (AD) but was withdrawn from the market due to its dose-dependent hepatotoxicity. Herein, we describe our efforts toward the discovery of a novel series of tacrine derivatives for cancer therapeutics. Intensive structural modifications of tacrine led to the identification of N-(4-{9-[(3S)-3-aminopyrrolidin-1-yl]-5,6,7,8-tetrahydroacridin-2-yl}pyridin-2-yl)cyclopropanecarboxamide hydrochloride ((S)-45, ZLWT-37) as a potent antiproliferative agent (GI50 = 0.029 μM for HCT116). In addition, ZLWT-37 exhibited lower inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) compared to tacrine. The in vitro studies demonstrated that ZLWT-37 could significantly induce apoptosis and arrest the cell cycle in the G2/M phase in HCT116 cells. The in vivo studies revealed that compound ZLWT-37 showed excellent antitumor efficacy in HCT116 xenograft tumor model and favorable pharmacokinetics profiles (F% = 28.70%) as well as low toxicity in the acute toxicity test with a median LD (LD50) of 380.3 mg/kg. Encouragingly, ZLWT-37 had no obvious hepatotoxicity, nephrotoxicity, and hematol. toxicity. Kinase assay suggested that ZLWT-37 possessed potent cyclin-dependent kinase 9 (CDK9) inhibitory activity (IC50 = 0.002 μM) and good selectivity over CDK2 (IC50 = 0.054 μM). Collectively, these findings indicate that compound ZLWT-37 is a promising anti-cancer agent that deserves further preclin. evaluation.

Bioorganic Chemistry published new progress about Antiproliferative agents. 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Name: 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Yang, Lichen; Semba, Kazuhiko; Nakao, Yoshiaki published the artcile< para-Selective C-H Borylation of (Hetero)Arenes by Cooperative Iridium/Aluminum Catalysis>, Reference of 660867-80-1, the main research area is selective carbon hydrogen bond activation borylation benzamide pyridine; iridium complex aluminum Lewis acid catalyst benzamide borylation; C-H activation; Lewis acids; boronate esters; iridium; regioselectivity.

Para-Selective C-H borylation of benzamides and pyridines was achieved by cooperative Ir/Al catalysis. A combination of Ir catalysts commonly employed for arene C-H borylation and bulky Al-based Lewis acid catalysts provides an unprecedented strategy for controlling the regioselectivity of C-H borylation to give variously substituted (hetero)arylboronates, which are versatile synthetic intermediates for complex multi-substituted aromatic compounds

Angewandte Chemie, International Edition published new progress about Aromatic compounds Role: SPN (Synthetic Preparation), PREP (Preparation) (multi-substituted). 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Reference of 660867-80-1.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Wu, Jia-Xue; Yao, Qing-Xia; Duan, Wen-Zeng; Li, Da-Cheng; Huang, Xian-Qiang; Dou, Jian-Min; Wang, Huai-Wei published the artcile< RhIII-Catalyzed heteroarylation of N-2,6-difluorophenyl arylamides with heteroaryl boronate esters>, Formula: C12H18BNO2, the main research area is aryl heteroaryl amide preparation regioselective; difluorophenyl arylamide heteroaryl boronate ester heteroarylation rhodium.

Herein, an efficient strategy to achieve aryl-heteroaryl formation via RhIII-catalyzed ortho-C(sp2)-H heteroarylation of (hetero)arenes with heterocyclic boronates using a readily removable N-2,6-difluorophenyl arylamide directing group has been disclosed. A variety of heteroaromatic boronates as the coupling partners were shown to be able to participate in this protocol, providing the desired heteroarylated products with high reactivity and good tolerance of functional groups. The achievement of this C(sp2)-H heteroarylation could potentially offer a route to synthesize heterocyclic drug mols. in medicinal chem.

Organic Chemistry Frontiers published new progress about Aromatic amides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Formula: C12H18BNO2.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Wollenburg, Marco; Moock, Daniel; Glorius, Frank published the artcile< Hydrogenation of Borylated Arenes>, Recommanded Product: 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, the main research area is hydrogenation stereoselective borylated arene rhodium catalyst; crystal structure mol boronic acid ester preparation; arene hydrogenation; boronic esters; cycloalkanes; heterocycles; synthetic building blocks.

A cis-selective hydrogenation of abundant aryl boronic acids and their derivatives catalyzed by rhodium cyclic (alkyl)(amino)carbene (Rh-CAAC) is reported. The reaction tolerates a variety of boron-protecting groups and provides direct access to a broad scope of saturated, borylated carbo- and heterocycles with various functional groups. The transformation is strategically important because the versatile saturated boronate products are difficult to prepare by other methods. The utility of the saturated cyclic building blocks was demonstrated by post-functionalization of the boron group.

Angewandte Chemie, International Edition published new progress about Aromatic hydrocarbons Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation) (borylated). 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Recommanded Product: 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Lesniak, Robert K.; Nichols, R. Jeremy; Schonemann, Marcus; Zhao, Jing; Gajera, Chandresh R.; Lam, Grace; Nguyen, Khanh C.; Langston, J. William; Smith, Mark; Montine, Thomas J. published the artcile< Discovery of 1H-Pyrazole Biaryl Sulfonamides as Novel G2019S-LRRK2 Kinase Inhibitors>, Electric Literature of 660867-80-1, the main research area is pyrazole biaryl sulfonamides preparation G2019S LRRK2 kinase inhibitor.

G2019S (GS) is the most prevalent mutation in the leucine rich repeat protein kinase 2 gene (LRRK2), a genetic predisposition that is common for Parkinson’s disease, as well as for some forms of cancer, and is a shared risk allele for Crohn’s disease. GS-LRRK2 has a hyperactive kinase, and although numerous drug discovery programs have targeted LRRK2 kinase, few have reached clin. development. We report the discovery and preliminary development of an entirely novel structural class of potent and selective GS-LRRK2 kinase inhibitors: biaryl-1H-pyrazoles.

ACS Medicinal Chemistry Letters published new progress about Crohn disease. 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Electric Literature of 660867-80-1.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Ding, Li; Pannecouque, Christophe; De Clercq, Erik; Zhuang, Chunlin; Chen, Fen-Er published the artcile< Improving Druggability of Novel Diarylpyrimidine NNRTIs by a Fragment-Based Replacement Strategy: From Biphenyl-DAPYs to Heteroaromatic-Biphenyl-DAPYs>, Formula: C12H18BNO2, the main research area is difluorobiphenyl diarylpyrimidine synthesis NNRTIs antiHIV solubility cytotoxicity.

A series of novel heteroaromatic-difluoro-biphenyl-diarylpyrimidines were designed as non-nucleoside anti-HIV inhibitors targeting reverse transcriptase by a fragment-based replacement strategy with the purpose of improving the druggability. Hopping five- or six-membered heterocycle groups on the biphenyl moiety as bioisosterism for intrinsically cyanophenyl gave 23 derivatives All of these compounds possessed excellent HIV-1 inhibitory activity in the nanomolar range. Among them, 12g (I) with a 4-pyridine group displayed excellent inhibitory activity toward WT and mutant HIV virus possessing significant selectivity. Moreover, this compound exhibited a decent improvement in druggability than etravirine and rilpivirine: (1) The hydrochloric acid salt of 12g (I) exhibited significantly improved water solubility in different pH conditions. (2) 12g (I) did not show apparent CYP enzymic inhibitory activity or acute toxicity. (3) Excellent oral bioavailability was also revealed (F = 126%, rats) in 12g. Collectively, these novel heteroaromatic-biphenyl-DAPYs represent promising drug candidates for HIV clin. therapy.

Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Formula: C12H18BNO2.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Vekariya, Rakesh H.; Lei, Wei; Ray, Abhisek; Saini, Surendra K.; Zhang, Sixue; Molnar, Gabriella; Barlow, Deborah; Karlage, Kelly L.; Bilsky, Edward J.; Houseknecht, Karen L.; Largent-Milnes, Tally M.; Streicher, John M.; Ananthan, Subramaniam published the artcile< Synthesis and Structure-Activity Relationships of 5'-Aryl-14-alkoxypyridomorphinans: Identification of a μ Opioid Receptor Agonist/δ Opioid Receptor Antagonist Ligand with Systemic Antinociceptive Activity and Diminished Opioid Side Effects>, Safety of 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, the main research area is MOR agonist DOR antagonist antinociceptive SAR side effects.

We previously identified a pyridomorphinan (6, SRI-22138) possessing a 4-chlorophenyl substituent at the 5′-position on the pyridine and a 3-phenylpropoxy at the 14-position of the morphinan as a mixed μ opioid receptor (MOR) agonist and δ/κ opioid receptor (DOR/KOR) antagonist with potent antinociceptive activity and diminished tolerance and dependence in rodents. Structural variations at the 5′- and 14-positions of this mol. gave insights into the structure-activity relationships for binding and functional activity. Subtle structural changes exerted significant influence, particularly on the ability of the compounds to function as agonists at the MOR. In vivo evaluation identified compound 20(I) (SRI-39067) as a MOR agonist/DOR antagonist that produced systemically active potent antinociceptive activity in tail-flick assay in mice, with diminished tolerance, dependence/withdrawal, reward liability, and respiratory depression vs. morphine. These results support the hypothesis that mixed MOR agonist/DOR antagonist ligands may emerge as novel opioid analgesics with reduced side effects.

Journal of Medicinal Chemistry published new progress about Analgesics. 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Safety of 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Ma, Haikuo; Chen, Qin; Zhu, Fang; Zheng, Jiyue; Li, Jiajun; Zhang, Hongjian; Chen, Shuaishuai; Xing, Haimei; Luo, Lusong; Zheng, Long Tai; He, Sudan; Zhang, Xiaohu published the artcile< Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor>, Reference of 660867-80-1, the main research area is Wnt hedgehog signaling inhibitor antitumor neoplasm pharmacokinetics; Antagonist; Cancer therapy; Hedgehog signaling pathway; Porcupine; Smoothened; Stem cell; Wnt signaling pathway.

Embryonic stem cell pathways such as hedgehog and Wnt pathways are central to the tumorigenic properties of cancer stem cells (CSC). Since CSCs are characterized by their ability to self-renew, form differentiated progeny, and develop resistance to anticancer therapies, targeting the Wnt and hedgehog signaling pathways has been an important strategy for cancer treatment. Although mols. targeting either Wnt or hedgehog are common, to the best of the knowledge, those targeting both pathways have not been documented. Here the authors report a small mol. (compound I) that inhibits both Wnt (IC50 = 0.5 nM) and hedgehog (IC50 = 71 nM) pathways based on reporter gene assays. The authors further identified that the mol. target of I for Wnt pathway inhibition was porcupine (a member of the membrane-bound O-acyltransferase family of proteins), a posttranslational modification node in Wnt signaling; while the target of I mitigating hedgehog pathway was Smoothened, a key G protein coupled receptor (GPCR) mediating hedgehog signal transduction. Preliminary anal. of structure-activity-relationship identified key functional elements for hedgehog/Wnt inhibition. In in vivo studies, compound I demonstrated good oral exposure and bioavailability while eliciting no overt toxicity in mice. An important consideration in cancer treatment is the potential therapeutic escape through compensatory activation of an interconnected pathway when only one signaling pathway is inhibited. Toward this end, compound I may not only lead to the development of new therapeutics for Wnt and hedgehog related cancers, but may also help to develop potential cancer treatment which needs to target Wnt and hedgehog signaling simultaneously.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Reference of 660867-80-1.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Fontaine, Fanny; Hequet, Arnaud; Voisin-Chiret, Anne-Sophie; Bouillon, Alexandre; Lesnard, Aurelien; Cresteil, Thierry; Jolivalt, Claude; Rault, Sylvain published the artcile< First identification of boronic species as novel potential inhibitors of the Staphylococcus aureus NorA efflux pump>, Recommanded Product: 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, the main research area is boron compound transport protein NorA Staphylococcus.

Overexpression of efflux pumps is an important mechanism of bacterial resistance that results in the extrusion of antimicrobial agents outside the bacterial cell. Inhibition of such pumps appears to be a promising strategy that could restore the potency of existing antibiotics. The NorA efflux pump of Staphylococcus aureus confers resistance to a wide range of unrelated substrates, such as hydrophilic fluoroquinolones, leading to a multidrug-resistance phenotype. Here, 150 heterocyclic boronic species were evaluated for their activity against susceptible and resistant strains of S. aureus. Twenty-four hit compounds, although inactive when tested alone, were found to potentiate ciprofloxacin activity by a 4-fold increase at concentrations ranging from 0.5 to 8 μg/mL against S. aureus 1199B, which overexpresses NorA. Boron-free analogs showed no biol. activity, thus revealing that the boron atom is crucial for biol. activity. This work describes the first reported efflux pump inhibitory activity of boronic acid derivatives

Journal of Medicinal Chemistry published new progress about Antibacterial agents. 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Recommanded Product: 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts