A5020620129- Cancer-related Molecular Pathways
- Multicomponent Synthesis of Heterocycles
- Protein Degradation and Inhibitors
- Advanced Breast Cancer Therapies
- Catalytic C–H Functionalization Methods
- Ubiquitin and proteasome pathways
- Chemical Synthesis and Analysis
- Synthesis and Reactivity of Heterocycles
- Asymmetric Synthesis and Catalysis
- Lung Cancer Research Studies
- Synthesis of heterocyclic compounds
- Synthesis and Reactions of Organic Compounds
- Synthesis and Characterization of Heterocyclic Compounds
- Asymmetric Hydrogenation and Catalysis
- Synthetic Organic Chemistry Methods
- Quinazolinone synthesis and applications
- Sulfur-Based Synthesis Techniques
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Various Chemistry Research Topics
- Coordination Chemistry and Organometallics
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and bioactivity of alkaloids
- Carbohydrate Chemistry and Synthesis
The Wistar Institute
2020-2023
Abzena (United States)
2021
Drexel University
2016-2019
Duquesne University
2015-2016
Texas Woman's University
1987
Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants, including relapsed tumors,...
Metalated arylmethylisonitriles readily add to 2-chloropyridines afford imidazo[1,5-a]pyridines. Analogous additions imidoyl chlorides and a chloroquinoline provide imidazoles an imidazo[1,5-a]quinolone which, like imidazo[1,5-a]pyridines, are valuable heterocycles for pharmaceutical synthesis.
Abstract Isocyanides are exceptional building blocks, the wide deployment of which in multicomponent and metal‐insertion reactions belies their limited availability. The first conjugate addition/alkylation to alkenyl isocyanides is described, addresses this deficiency. An array organolithiums, magnesiates, enolates, metalated nitriles add conjugately β‐ β,β‐disubstituted arylsulfonyl rapidly assemble diverse isocyanide scaffolds. intermediate efficiently trapped with electrophiles generate...
Oxazoles are rapidly assembled through a sequential deprotonation–condensation of Asmic, anisylsulfanylmethylisocyanide, with esters followed by sulfanyl–lithium exchange–trapping. Deprotonating Asmic affords metalated isocyanide that efficiently traps to afford oxazoles bearing versatile C-4 anisylsulfanyl substituent. Interchange the substituent is readily achieved first-in-class sulfur–lithium exchange–electrophilic trapping sequence whose versatility illustrated in three-step synthesis...
Copper iodide catalyzes the conjugate addition of organometallic and heteroatom nucleophiles to isocyano enones afford oxazoles. A range enolates, metalated nitriles, amines, thiols undergo catalyzed cyclic acyclic oxoalkene isocyanides. Mechanistic studies suggest that copper complexation facilitates nucleophilic attack on enone generate an enolate cyclizes onto isocyanide leading a variety substituted or ring-fused
Asmic addresses the long-standing challenge of alkylating isocyanides, providing access to isocyanides with diverse substitution patterns. The o-anisylsulfanyl group serves a critical dual role by facilitating deprotonation–alkylation and latent nucleophilic site through an unusual arylsulfanyl–lithium exchange.
EtSiCl3-treated silica gel, ‘C-2 silica,’ proved exceptionally effective for purifying isocyanides that are otherwise irreversibly adsorbed during gel chromatography. Purification of a prototypical isocyanide on several chromatographic matrices provided valuable insight into the requirements silica-sensitive isocyanides. EtSiCl3-modified optimal as solid phase, providing up to 90% recovery pure fail elute purification.
A copper iodide–Pyox complex catalyzes the first conjugate addition of diverse sulfur, nitrogen, and carbon nucleophiles to isocyanoalkenes. The anionic generates metalated isocyanoalkanes capable SNi displacements, providing a rapid route series functionalized, cyclic isocyanoalkanes. Cu(I)I–Pyox efficiently first-in-class affording range complex, functionalized that are otherwise challenging synthesize while laying foundation for catalytic reactions maintain isocyanide group.
Substituted imidazoles are readily prepared by condensing the versatile isocyanide Asmic, anisylsulfanylmethylisocyanide, with nitrogenous π-electrophiles. Deprotonating Asmic lithium hexamethyldisilazide effectively generates a potent nucleophile that efficiently intercepts nitrile and imine electrophiles to afford imidazoles. In situ cyclization imidazole is promoted conjugate acid, hexamethyldisilazane, which facilitates requisite series of proton transfers. The rapid formation...
Abstract The modular and rapid synthesis is based on the reaction of various acyclic 6‐7‐membered isocyano enones with diverse carbon or heteroatom nucleophiles such as dicarbonyl compounds, malonitrile, nitromethane, benzylamine 4‐methylbenzenethiol.
<div>Abstract<p>Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants,...
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<div>Abstract<p>Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants,...
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<div>Abstract<p>Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants,...
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<div>Abstract<p>Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants,...
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>
<div>Abstract<p>Triple-negative breast cancers (TNBC) frequently inactivate p53, increasing their aggressiveness and therapy resistance. We identified an unexpected protein vulnerability in p53-inactivated TNBC designed a new PROteolysis TArgeting Chimera (PROTAC) to target it. Our PROTAC selectively targets MDM2 for proteasome-mediated degradation with high-affinity binding VHL recruitment. loss p53 mutant/deleted cells two-dimensional/three-dimensional culture patient explants,...
<p>Supplementary Materials and Methods, Tables S1-S3, Figures S1-S7</p>