A5086746388- Catalytic C–H Functionalization Methods
- Catalytic Cross-Coupling Reactions
- Innovative Microfluidic and Catalytic Techniques Innovation
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Radical Photochemical Reactions
- Chemical Synthesis and Analysis
- Asymmetric Synthesis and Catalysis
- Synthetic Organic Chemistry Methods
- Sulfur-Based Synthesis Techniques
- Machine Learning in Materials Science
- Computational Drug Discovery Methods
- Chemical Reactions and Isotopes
- Oxidative Organic Chemistry Reactions
- Asymmetric Hydrogenation and Catalysis
- Synthesis and Catalytic Reactions
- Synthesis and Biological Evaluation
- SARS-CoV-2 and COVID-19 Research
- Pharmacogenetics and Drug Metabolism
- Nanomaterials for catalytic reactions
- Organoboron and organosilicon chemistry
- Adenosine and Purinergic Signaling
- Neuroblastoma Research and Treatments
- COVID-19 Clinical Research Studies
- Chemical synthesis and alkaloids
Pfizer (United States)
2019-2025
University of Pennsylvania
2011-2020
High Throughput Biology (United States)
2016-2019
Monell Chemical Senses Center
2018
Philadelphia University
2009-2017
California University of Pennsylvania
2017
Merck & Co., Inc., Rahway, NJ, USA (United States)
2012-2014
University of Sussex
2006-2010
The worldwide outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Alongside vaccines, antiviral therapeutics are an important part the healthcare response to countering ongoing threat presented COVID-19. Here, we report discovery and characterization PF-07321332, orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human activity excellent off-target selectivity vivo safety profiles. PF-07321332...
Breaking through the milligram floor When chemists synthesize compounds, threshold for success is at least a of product. This has been true decades—even though biochemical assays have long since descended into microgram territory—and results in part from constraints characterization methods. Buitrago Santanilla et al. present an automated dosing and protocol optimizing chemical reaction conditions on scale. allowed them to screen numerous base ligand combinations catalytic C-N bond-forming...
High-throughput experimentation (HTE) has revolutionized the pharmaceutical industry, most notably allowing for rapid screening of compound libraries against therapeutic targets. The past decade also witnessed extension HTE principles toward realm small-molecule process chemistry. Today, major companies have created dedicated groups within their development teams, invested in automation technology to accelerate screening, or both. industry's commitment accelerating led innovations space....
DNA-encoded library (DEL) technology is a powerful tool commonly used by the pharmaceutical industry for identification of compounds with affinity to biomolecular targets. Success in this endeavor lies sampling diverse chemical libraries. However, current DELs tend be deficient C(sp3) carbon counts. We report unique solutions challenge increasing both diversity these libraries and their counts merging Ni/photoredox dual catalytic C(sp2)-C(sp3) cross-coupling as well photoredox-catalyzed...
Methane borylation in a cyclohexane sea Although methane combusts readily at high temperatures, it is generally the hardest hydrocarbon to transform under gentler conditions, owing its particularly strong C-H bonds. Cook et al. now show that soluble rhodium, iridium, and ruthenium catalysts can slice through these bonds add boron substituents 150°C. Smith report iridium-catalyzed reaction using phosphine ligands enhance activity. Both studies were performed solvent, revealing remarkable...
A mechanistically distinct, Ni/photoredox-catalyzed arylation of unprotected, native thiols (<italic>e.g.</italic>, cysteine residues) is reported – a process initiated through visible light-promoted, hydrogen atom transfer (HAT) event under ambient conditions.
The past decade has witnessed the rapid development of radical generation strategies and their applications in C-C bond-forming reactions. Most these processes require initiators, transition metal catalysts, or organometallic reagents. Herein, we report discovery a simple organic system (2-azaallyl anions) that enables coupling reactions under transition-metal-free conditions. Deprotonation N-benzyl ketimines generates semistabilized 2-azaallyl anions behave as "super-electron-donors" (SEDs)...
High-throughput experimentation (HTE) has the potential to improve our understanding of organic chemistry by systematically interrogating reactivity across diverse chemical spaces. Notable bottlenecks include few publicly available large-scale datasets and need for facile interpretation these data's hidden insights. Here we report development a high-throughput analyser, robust statistically rigorous framework, which is applicable any HTE dataset regardless size, scope or target reaction...
In early 2020, severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infections leading to COVID-19 disease reached a global level the World Health Organization (WHO) declaration of pandemic. Scientists around globe rapidly responded try and discover novel therapeutics repurpose extant drugs treat disease. This work describes preclinical discovery efforts that led invention PF-07321332 (nirmatrelvir, 14), potent orally active inhibitor SARS CoV-2 main protease (Mpro) enzyme. At outset...
Abstract A unique chemo‐ and regioselective α‐ γ‐arylation of palladium azapentadienyl intermediates is presented. Two distinct catalysts sets conditions successfully controlled the regioselectivity arylation. These methods provide first umpolung C−H functionalization enable divergent synthesis allylic amine enamine derivatives, which are significant interest in pharmaceutical industry.
Vinca-domain ligands are compounds that bind to tubulin at its inter-heterodimeric interface and favour heterogeneous protofilament-like assemblies, giving rise helices rings. This is the basis for their inhibition of microtubule assembly, antimitotic activities use in anticancer chemotherapy. Ustiloxins vinca-domain with a well established total synthesis. A 2.7 Å resolution structure ustiloxin D bound vinca domain embedded complex two tubulins stathmin-like RB3 (T2R) has been determined....
A regioselective arylation of 1,1,3-triaryl-2-azaallyl anions with aryl chlorides is described. The palladium-NIXANTPHOS-based catalyst affords diarylmethylamine derivatives in good yield and without product isomerization. gram scale sequential one-pot ketimine synthesis/arylation protocol was also developed.
In this Article, a strategy to obtain highly enantioselective catalysts for the Claisen rearrangement of allyloxy- and propargyloxy-indoles is outlined. Ultimately, copper BOX palladium BINAP or PHOX were discovered as superior in catalyzing rearrangements proparyloxy-substituted indoles generate oxindoles bearing allyl- allenyl-substituted quaternary centers. This method proved be tolerant broad range functional groups. Tandem reactions silyl-allene products provide rapid access variety...
An efficient cross-coupling reaction of aryl halides and nitromethane was developed with the use parallel microscale experimentation. The arylnitromethane products are precursors for numerous useful synthetic products. method their direct conversion to corresponding oximes aldehydes in a one-pot operation has been discovered. process exploits inexpensive as carbonyl equivalent, providing mild convenient formylation that is compatible many functional groups.
The first asymmetric synthesis of α-allyl-α-aryl α-amino acids by means a three-component coupling α-iminoesters, Grignard reagents, and cinnamyl acetate is reported. Notably, the enolate from tandem process provides much higher level reactivity selectivity than same generated via direct deprotonation, presumably due to differences in solvation/aggregation state. A novel method for removal homoallylic amine protecting group delivers free congeners. α-allyl offers generate further valuable...
Aryl bromides are known to be challenging substrates in the decarboxylative cross-electrophile coupling with redox-active NHP esters-the majority of such processes utilize aryl iodides. Herein, we describe development conditions that suitable for esters and a wide range (hetero)aryl bromides. The key advances allowed use this reaction (1) identification ligand L3 as an optimal electron-neutral deficient (2) significant improvement yield iodide salts excess heterogenous zinc impart reaction....
Hematopoietic progenitor kinase 1 (HPK1/MAP4K1) represents a high interest target for the treatment of cancer through an immune-mediated mechanism. Herein we present highlights drug discovery campaign within lactam/azalactam series inhibitors that yielded small molecule (
Herein we describe a set of privileged and stereocomplementary ene-reductase enzymes which, when induced by light aided an exogenous photocatalyst, catalyze the coupling (hetero)aryl halides alkenes in asymmetric intermolecular hydroarylation process. Thus, carbon scaffolds containing C(sp2)-C(sp3) bonds are synthesized enzymatically from simple precursors excellent enantiomeric excess. Furthermore, intramolecular is achieved through tethering to their alkene reaction partners this manner...
A metal-free strategy to access tertiary difluoromethylene-containing molecules from RCF 2 H (R = aryl, H, F) precursors, vinyl-pinacol boronic ester (BPin) reagents, and proradical reagents is reported.