660867-80-1 Archives - Page 3 of 4 - Alcohols-buliding-blocks

Chen, Jian Jeffrey’s team published research in Bioorganic & Medicinal Chemistry Letters in 2015-02-15 | 660867-80-1

Bioorganic & Medicinal Chemistry Letters published new progress about Alzheimer disease. 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Computed Properties of 660867-80-1.

Chen, Jian Jeffrey; Liu, Qingyian; Yuan, Chester; Gore, Vijay; Lopez, Patricia; Ma, Vu; Amegadzie, Albert; Qian, Wenyuan; Judd, Ted C.; Minatti, Ana E.; Brown, James; Cheng, Yuan; Xue, May; Zhong, Wenge; Dineen, Thomas A.; Epstein, Oleg; Human, Jason; Kreiman, Charles; Marx, Isaac; Weiss, Matthew M.; Hitchcock, Stephen A.; Powers, Timothy S.; Chen, Kui; Wen, Paul H.; Whittington, Douglas A.; Cheng, Alan C.; Bartberger, Michael D.; Hickman, Dean; Werner, Jonathan A.; Vargas, Hugo M.; Everds, Nancy E.; Vonderfecht, Steven L.; Dunn, Robert T. II; Wood, Stephen; Fremeau, Robert T. Jr.; White, Ryan D.; Patel, Vinod F. published the artcile< Development of 2-aminooxazoline 3-azaxanthenes as orally efficacious β-secretase inhibitors for the potential treatment of Alzheimer's disease>, Computed Properties of 660867-80-1, the main research area is aminooxazoline azaxanthene derivative preparation oral beta secretase inhibitor Alzheimer’s; 3-Azaxanthene; Alzheimer’s disease (AD); Aminooxazoline; Amyloid; Aβ peptides; Xanthene; β-Secretase (BACE1).

The β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is one of the most hotly pursued targets for the treatment of Alzheimer’s disease. We used a structure- and property-based drug design approach to identify 2-aminooxazoline 3-azaxanthenes as potent BACE1 inhibitors which significantly reduced CSF and brain Aβ levels in a rat pharmacodynamic model. Compared to the initial lead 2, compound 28 exhibited reduced potential for QTc prolongation in a non-human primate cardiovascular safety model.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Dong, Yan’s team published research in Bioorganic & Medicinal Chemistry in 2015-11-01 | 660867-80-1

Bioorganic & Medicinal Chemistry published new progress about Amide group (in Porcupine antagonists). 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Product Details of C12H18BNO2.

Dong, Yan; Li, Kehuang; Xu, Zhixiang; Ma, Haikuo; Zheng, Jiyue; Hu, Zhilin; He, Sudan; Wu, Yiyuan; Sun, Zhijian; Luo, Lusong; Li, Jiajun; Zhang, Hongjian; Zhang, Xiaohu published the artcile< Exploration of the linkage elements of porcupine antagonists led to potent Wnt signaling pathway inhibitors>, Product Details of C12H18BNO2, the main research area is protein palmitoyltransferase Porcupine antagonist synthesis inhibitor Wnt signaling secretion; Antagonist; Cancer therapy; Porcupine; Scaffold hybridization; Wnt signaling pathway.

The Wnt signaling pathway is a pivotal developmental pathway. It operates through control of cellular functions such as proliferation, differentiation, migration and polarity. Aberrant Wnt signaling has been implicated in the formation and metastasis of tumors. Porcupine is a component of the Wnt signaling pathway. It is a member of the membrane-bound O-acyltransferase family of proteins. Porcupine catalyzes the palmitoylation of Wnt proteins, a process which is essential to their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from two known porcupine inhibitor classes. The leading compound 62 demonstrated subnanomolar (IC50 0.11 nM) inhibition of Wnt signaling in a paracrine cellular reporter gene assay. Compound 62 also potently inhibited Wnt secretion into culture medium, an indication of direct inhibition of the porcupine protein. Furthermore, compound 62 showed excellent chem., plasma and liver microsomal stabilities. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Tian, Ya-Ming’s team published research in Journal of the American Chemical Society in 2020-10-21 | 660867-80-1

Journal of the American Chemical Society published new progress about Aryl chlorides Role: RCT (Reactant), RACT (Reactant or Reagent). 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.

Tian, Ya-Ming; Guo, Xiao-Ning; Krummenacher, Ivo; Wu, Zhu; Nitsch, Joern; Braunschweig, Holger; Radius, Udo; Marder, Todd B. published the artcile< Visible-Light-Induced Ni-Catalyzed Radical Borylation of Chloroarenes>, Safety of 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, the main research area is chloro nickel carbene preparation catalyzed radical borylation chloroarene; crystal structure imidazolylidene nickel chloride; mol structure imidazolylidene nickel chloride; arylborane preparation.

A highly selective and general photoinduced C-Cl borylation protocol that employs [Ni(IMes)2] (IMes = 1,3-dimesitylimidazoline-2-ylidene) for the radical borylation of chloroarenes is reported. This photoinduced system operates with visible light (400 nm) and achieves borylation of a wide range of chloroarenes with B2pin2 at room temperature in excellent yields and with high selectivity, thereby demonstrating its broad utility and functional group tolerance. Mechanistic studies suggest that the borylation reactions proceed via a radical process. EPR studies demonstrate that [Ni(IMes)2] undergoes very fast Cl atom abstraction from aryl chlorides to give [Ni(I)(IMes)2Cl] and aryl radicals. Control experiments indicate that light promotes the reaction of [Ni(I)(IMes)2Cl] with aryl chlorides generating addnl. aryl radicals and [Ni(II)(IMes)2Cl2]. The aryl radicals react with an anionic sp2-sp3 diborane [B2pin2(OMe)]- formed from B2pin2 and KOMe to yield the corresponding borylation product and the [Bpin(OMe)]•- radical anion, which reduces [Ni(II)(IMes)2Cl2] under irradiation to regenerate [Ni(I)(IMes)2Cl] and [Ni(IMes)2] for the next catalytic cycle.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Mikami, Satoshi’s team published research in Chemical & Pharmaceutical Bulletin in 2017-11-30 | 660867-80-1

Chemical & Pharmaceutical Bulletin published new progress about Bioavailability. 660867-80-1 belongs to class alcohols-buliding-blocks, and the molecular formula is C12H18BNO2, Electric Literature of 660867-80-1.

Mikami, Satoshi; Kawasaki, Masanori; Ikeda, Shuhei; Negoro, Nobuyuki; Nakamura, Shinji; Nomura, Izumi; Ashizawa, Tomoko; Kokubo, Hironori; Hoffman, Isaac Dylan; Zou, Hua; Oki, Hideyuki; Uchiyama, Noriko; Hiura, Yuuto; Miyamoto, Maki; Itou, Yuuki; Nakashima, Masato; Iwashita, Hiroki; Taniguchi, Takahiko published the artcile< Discovery of a novel series of pyrazolo[1,5-a]pyrimidine-based phosphodiesterase 2A inhibitors structurally different from N-((1S)-1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915), for the treatment of cognitive disorders>, Electric Literature of 660867-80-1, the main research area is pyrazolopyrimidine preparation phosphodiesterase inhibitor SAR; intramolecular hydrogen bond; phospodiesterase 2A; phototoxicity; pyrazolo[1,5-a]pyrimidine; schizophrenia; structure-based drug design.

This article described a drug design strategy for a new series of lead compounds structurally distinct from the clin. candidate TAK-915, and subsequent medicinal chem. efforts to optimize potency, selectivity over other PDE families, and other preclin. properties including in-vitro phototoxicity and in-vivo rat plasma clearance. These efforts resulted in the discovery of N-((1S)-2-hydroxy-2-methyl-1-(4-(trifluoromethoxy)phenyl)propyl)-6-methyl-5-(3-methyl-1H-1,2,4-triazol-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide, which robustly increased 3′,5′-cyclic guanosine monophosphate (cGMP) levels in the rat brain following an oral dose, and moreover, attenuated MK-801-induced episodic memory deficits in a passive avoidance task in rats. These data provide further support to the potential therapeutic utility of PDE2A inhibitors in enhancing cognitive performance.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Gabriel, Christopher M’s team published research in Organic Letters in 2017-01-06 | 660867-80-1

Organic Letters published new progress about Amidation. 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.

Gabriel, Christopher M.; Lee, Nicholas R.; Bigorne, Florence; Klumphu, Piyatida; Parmentier, Michael; Gallou, Fabrice; Lipshutz, Bruce H. published the artcile< Effects of Co-solvents on Reactions Run under Micellar Catalysis Conditions>, Name: 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, the main research area is cosolvent water micelle organic reaction TPGS750M green E factor.

The impact of varying percentages of an organic solvent added to reactions run in aqueous nanomicelles as the reaction medium was studied. Issues such as rates of reaction, percent conversion, and yield, as well as various practical aspects (e.g., effect on stirring, etc.), are discussed, leading to an operationally simple method for the general improvement of potentially problematic systems across a broad range of reaction types, in particular for reactions run at scale.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Yang, Lichen’s team published research in Journal of the American Chemical Society in 2019-05-15 | 660867-80-1

Journal of the American Chemical Society published new progress about Benzamides 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, Related Products of 660867-80-1.

Yang, Lichen; Uemura, Nao; Nakao, Yoshiaki published the artcile< meta-Selective C-H Borylation of Benzamides and Pyridines by an Iridium-Lewis Acid Bifunctional Catalyst>, Related Products of 660867-80-1, the main research area is meta selective borylation benzamide pyridine iridium aluminum bifunctional catalyst; borane pyridyl benzamide derivative preparation.

The authors report herein the Ir-catalyzed meta-selective C-H borylation of benzamides by using a newly designed 2,2′-bipyridine (bpy) ligand bearing an alkylaluminum biphenoxide moiety. The authors also demonstrate the Ir-catalyzed C3-selective C-H borylation of pyridine with a 1,10-phenanthroline (Phen) ligand bearing an alkylborane moiety. Probably the Lewis acid-base interaction between the Lewis acid moiety and the aminocarbonyl group or the sp2-hybridized N atom accelerates the reaction and controls the site-selectivity.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Heinrich, Timo’s team published research in Journal of Medicinal Chemistry in 2013-02-14 | 660867-80-1

Journal of Medicinal Chemistry published new progress about Drug discovery (fragment-based). 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.

Heinrich, Timo; Seenisamy, Jeyaprakashnarayanan; Emmanuvel, Lourdusamy; Kulkarni, Santosh S.; Bomke, Joerg; Rohdich, Felix; Greiner, Hartmut; Esdar, Christina; Krier, Mireille; Graedler, Ulrich; Musil, Djordje published the artcile< Fragment-Based Discovery of New Highly Substituted 1H-Pyrrolo[2,3-b]- and 3H-Imidazolo[4,5-b]-Pyridines as Focal Adhesion Kinase Inhibitors>, Name: 2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, the main research area is pyrrolopyridine imidazolopyridine preparation focal adhesion kinase inhibitor.

Focal adhesion kinase (FAK) is considered as an attractive target for oncol., and small-mol. inhibitors are reported to be in clin. testing. In a surface plasmon resonance (SPR)-mediated fragment screening campaign, we discovered bicyclic scaffolds like 1H-pyrazolo[3,4-d]pyrimidines binding to the hinge region of FAK. By an accelerated knowledge-based fragment growing approach, essential pharmacophores were added. The establishment of highly substituted unprecedented 1H-pyrrolo[2,3-b]pyridine derivatives provided compounds with submicromolar cellular FAK inhibition potential, e.g. I. The combination of substituents on the bicyclic templates and the nature of the core structure itself have a significant impact on the compounds FAK selectivity. Structural anal. revealed that the appropriately substituted pyrrolo[2,3-b]pyridine induced a rare helical DFG-loop conformation. The discovered synthetic route to introduce three different substituents independently paves the way for versatile applications of the 7-azaindole core.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts