A5101564301- Electric Motor Design and Analysis
- Heat Transfer and Optimization
- Sensorless Control of Electric Motors
- Crystallization and Solubility Studies
- Sulfur-Based Synthesis Techniques
- Synthetic Organic Chemistry Methods
- Magnetic Properties and Applications
- Innovative Microfluidic and Catalytic Techniques Innovation
- Engineering Applied Research
- Radical Photochemical Reactions
- Business Process Modeling and Analysis
- Chemical Synthesis and Reactions
- Petri Nets in System Modeling
- Microstructure and Mechanical Properties of Steels
- Magnetic Bearings and Levitation Dynamics
- Heat Transfer and Boiling Studies
- Synthesis and Catalytic Reactions
- Geotechnical Engineering and Underground Structures
- Metallurgy and Material Forming
- Soil Mechanics and Vehicle Dynamics
- Heat Transfer Mechanisms
- Marine Sponges and Natural Products
- X-ray Diffraction in Crystallography
- Chemical synthesis and alkaloids
- Epoxy Resin Curing Processes
Merck & Co., Inc., Rahway, NJ, USA (United States)
2018-2024
Korea Institute of Machinery and Materials
2023
Hankuk Carbon (South Korea)
2023
Pusan National University
1998-2016
Seoul National University
2016
Pusan National University Yangsan Hospital
2016
Kyung Hee University
2013
Hyundai Engineering (South Korea)
2012-2013
Convergence
2013
Chungnam National University
2012-2013
Biocatalytic oxidations are an emerging technology for selective C-H bond activation. While promising a range of oxidations, practical use enzymes catalyzing aerobic hydroxylation is presently limited by their substrate scope and stability under industrially relevant conditions. Here, we report the engineering application non-heme iron α-ketoglutarate-dependent dioxygenase direct stereo- regio-selective non-native fluoroindanone en route to oncology treatment belzutifan, replacing five-step...
Belzutifan (MK-6482) is an FDA-approved hypoxia inducible factor 2α inhibitor for the treatment of Von Hippel–Lindau disease-associated renal cell carcinoma. One key synthetic steps enzymatic benzylic hydroxylation indanone. Prior to optimization, reactions required dilute conditions (100 volumes water) and high enzyme loading (50 wt %) achieve target conversion, which was unsuitable a long-term manufacturing process. Reduction reaction introduced additional complexity large-scale operations...
An improved synthesis has been developed for belzutifan, a novel HIF-2α inhibitor the treatment of Von Hippel–Lindau (VHL) disease-associated renal cell carcinoma (RCC). The efficiency previous supply and commercial routes was encumbered by lengthy 5-step sequence, needed to install chiral benzylic alcohol traditional methods. Identification directed evolution FoPip4H, an iron/α-ketoglutarate dependent hydroxylase, enabled direct enantioselective C–H hydroxylation simple indanone starting...
To identify candidate genes that could be used as diagnostic and therapeutic targets for hepatocellular carcinoma (HCC), we searched the are overexpressed in HCC by combining representational difference analysis microarray. Genes such glypican‐3 (GPC3), insulin‐like growth factor 2, long‐chain fatty‐acid‐coenzyme A ligase 4, farnesyl diphosphate synthase were frequently identified our screening. Northern blot with these four confirmed their overexpression HCC. Among them found GPC3...
In this paper, various key points in the rotor design of a low-cost permanent-magnet-assisted synchronous reluctance motor (PMa-SynRM) are introduced and their effects studied. Finite-element approach has been utilized to show these parameters on developed average electromagnetic torque total d-q inductances. One features considered is magnetization permanent magnets mounted core using stator windings. This feature will cause reduction cost ease manufacturing. Effectiveness procedure...
The development and mechanistic investigation of a nickel-catalyzed sulfonylation aryl bromides is disclosed. reaction proceeds in good yields for variety substrates utilizes an inexpensive, stench-free, inorganic sulfur salt (K2 S2 O5 ) as uniquely effective SO2 surrogate. active oxidative addition complex was synthesized, isolated, fully characterized by combination NMR spectroscopy X-ray crystallography analysis. use the isolated both stoichiometric catalytic reactions revealed that...
A nickel-catalyzed sulfonylation reaction was discovered and developed into a robust process for the manufacturing of belzutifan, an FDA-approved treatment Von Hippel-Lindau disease-associated renal cell carcinoma. The proceeds via reductive sulfinylation utilizing two insoluble salts (potassium metabisulfite potassium formate), followed by methylation with nontoxic methylating reagent (trimethylphosphate). doubly heterogeneous nature proved difficult to scale due mixing particle size...
Keratin is an important protein used for wound healing and tissue recovery. In this study, keratin was first extracted from raw materials chemically modified to obtain stable (m-keratin). The m-keratin were examined by Raman spectroscopy. molecular weight of the analysed SDS–PAGE. then blended with poly(hydroxybutylate-co-hydroxyvalerate) (PHBV) electrospun afford nanofibrous mats. These mats characterized field emission scanning electron microscopy (FE-SEM), spectroscopy chemical analysis...
Abstract The 5.98 inch‐sized World's first flexible OLED display has been developed and launched mass production on smartphone with extremely light, thin curved shape, successfully. We have employed ELA‐TFT PI backplane, Face‐sealing encapsulation, Laser‐assisted glass release back‐plate lamination process. These technologies enable panel reliability as well inherent characteristics. For commercializing OLED, technical barriers challenges TFT device, design various process including LG...
Belzutifan has been approved recently by the U.S. Food and Drug Administration (FDA) for treating patients with certain types of Von Hippel-Lindau (VHL) disease-associated tumors. Although a commercial synthetic process established to make belzutifan, further optimized fewer steps, improved cost-effectiveness, smaller environmental footprint is always in demand. In new route, single-step biocatalytic hydroxylation reaction was used replace five chemical steps required previous route....
A four-step synthesis of the indanone core belzutifan (MK-6482) is described. This route starts from commodity raw material dihydrocoumarin and was successfully demonstrated on a large scale to produce 11 in belzutifan, an FDA-approved first-in-class therapy for treatment patients with certain types Von Hippel–Lindau disease-associated tumors.
Fatty acid‐CoA ligase 4 (FACL4) is a central enzyme controlling the unesterified arachidonic acid (AA) level in cells. It has been shown that FACL4 blocks apoptosis and promotes colon carcinogenesis by lowering cellular of AA. Consistent with this, upregulated adenocarcinoma. The status other tumors including hepatocellular carcinoma (HCC) not known. Here, we report overexpressed human HCC compared adjacent normal liver tissues. mRNA protein were 5 out 12 (41.7%) 3 8 (37.5%) cases HCC,...
We report the development of a modified Kornblum oxidation mediated by 2-picoline N-oxide for synthesis belzutifan that circumvented safety and stench problems associated with original clinical supply route conditions. A robust quench crude bromination stream 1,3-dimethoxybenzene 2,6-lutidine enabled single-solvent through-process avoided isolation mutagenic intermediate resulted in significantly lower process mass intensity. ternary-solvent, constant-volume distillation was then used to...
A photoaddition−cycloreversion strategy applicable to enantiospecific synthesis of natural byssochlamic acid and its enantiomer was developed in which porcine liver esterase (PLE) catalyzed hydrolysis 24 used desymmetrize this dimethyl ester give (R)-25. Analogous PLE 32 bis(methylthio)methyl 48, while highly regioselective, gave racemic half acids 33 49, respectively. Stepwise coupling (±)-49 (R)-46, the latter derived from 25, afforded diolide 52, upon irradiation exo,exo exo,endo [2 + 2]...
ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTSynthesis of Grazoprevir, a Potent NS3/4a Protease Inhibitor for the Treatment Hepatitis C VirusFeng Xu*Feng XuDepartment Process Research and Development, MRL, Merck & Co., Inc., Rahway, New Jersey 07065, United States*E-mail: [email protected]More by Feng Xuhttp://orcid.org/0000-0003-1949-324X, Jungchul KimJungchul KimDepartment StatesMore Kim, Jacob WaldmanJacob WaldmanDepartment Waldman, Tao WangTao WangDepartment Wang, Paul DevinePaul...
As a liquid film covering an array of micro- or nanoscale pillars lamellae evaporates, its meniscus pulls the elastic patterns together because capillary effects, leading to clustering slender microstructures. While this elastocapillary coalescence may imply various useful applications, it is detrimental semiconductor manufacturing process called spin drying, where rinses patterned wafers until drying. To understand transient mechanism underlying such self-organization during and after...
Abstract To deepen understanding of diffusion-controlled crosslinking, molecular dynamics (MD) simulations are carried out by taking the diffusion image 3,3′-diamino diphenyl sulfone (3,3′-DDS) and polyethersulfone (PES) with epoxy resin varying temperatures from 393.15 to 473.15 K over crosslinking conversion 0–85%. The PES 3,3′-DDS into bulk increased increasing temperature as a result enhanced mobility molecules when difference between glass-transition ( T g ) curing temperature. Beyond...
Background. There has been little information reported about the genetic event concerning pathophysiology of varicose vein (VV). objectives. The purpose this study was to examine differentiation gene expression in wall VV using complementary deoxyribonucleic acid (cDNA) microarrays. Methods. performed with four pairs VVs and control veins (CVs). cDNA specimens were prepared from ribonucleic acid–isolated patients who underwent venous obliteration, radiofrequency, as well CVs those...
Routes have been developed for the stereocontrolled elaboration of two highly functionalized sectors spongistatin 1. The approach to ring F takes advantage B-alkyl Suzuki−Miyaura coupling install C44−C45 bond. E-ring pyran moiety was generated by acylation an α-sulfonyl carbanion, stereogenic centers which were incorporated sequential asymmetric aldol reactions.
Apoptosis is regulated by interaction of antiapoptotic Bcl-2 family proteins with various proapoptotic proteins, several which are also members the family. BNIP3 (formerly NIP3) a mitochondrial protein classified in based on limited sequence homology-3 (BH3) domain and COOH-terminal transmembrane domain. Sequence comparison has indicated that there human homologs this protein, like BNIP3L, Nix BNIP3. We have cloned new member from cDNA library prepared dermal papilla cells designated as...
Abstract A photochemical synthetic method to access sulfones from aryl halides and sodium alkylsulfinates in the presence of CuCl is reported. Regio‐ chemoselectivity for sulfonylation observed polyhalogenated arenes. Mechanistic studies indicate that a copper sulfinate reagent formed situ based on NMR experiments. Potential reaction intermediates, including excited state are studied using density functional theory calculations reveal energetically accessible non‐planar triplet geometries.