A5022233903- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- Synthetic Organic Chemistry Methods
- Cyclopropane Reaction Mechanisms
- Carbohydrate Chemistry and Synthesis
- Catalytic C–H Functionalization Methods
- Synthesis and Catalytic Reactions
- HIV/AIDS drug development and treatment
- Ion Channels and Receptors
- Hepatitis C virus research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Click Chemistry and Applications
- Chemical synthesis and alkaloids
- Catalytic Cross-Coupling Reactions
- Asymmetric Synthesis and Catalysis
- Pain Mechanisms and Treatments
- Crystallography and molecular interactions
- Bioactive Compounds and Antitumor Agents
- Analytical Chemistry and Chromatography
- Asymmetric Hydrogenation and Catalysis
- Herbal Medicine Research Studies
- Computational Drug Discovery Methods
- Catalytic Alkyne Reactions
- Phytochemicals and Antioxidant Activities
AbbVie (United States)
2015-2024
AbbVie (Japan)
2021
Emory University
2021
Abbott (United Kingdom)
2012
Abbott Fund
2010
GlaxoSmithKline (United Kingdom)
2010
University of Wisconsin–Madison
2000-2009
Merck & Co., Inc., Rahway, NJ, USA (United States)
2006
West Virginia University
2004-2006
Abbott (United States)
2006
1-Benzyl-5-aryltetrazoles were discovered to be novel antagonists for the P2X(7) receptor. Structure-activity relationship (SAR) studies conducted around both benzyl and phenyl moieties. In addition, importance of regiochemical substitution on tetrazole was examined. Compounds evaluated activity inhibit calcium flux in human rat recombinant cell lines using fluorometric imaging plate reader technology. Analogues also assayed their ability IL-1beta release P2X(7)-mediated pore formation THP-1...
DNA-encoded libraries have proven their tremendous value in the identification of new lead compounds for drug discovery. To access chemical space, many methods emerged to transpose traditional mol-scale reactivity nmol-scale, on-DNA chemistry. However, procedures with a greater fraction C(sp3) content are still limited, and need "escape from flatland" more readily remains. Herein, we report Giese addition install highly functionalized bicyclo[1.1.1]pentanes (BCPs) using...
The transient receptor potential vanilloid-1 (TRPV1) channel is involved in the development and maintenance of pain participates regulation temperature. activated by diverse agents, including capsaicin, noxious heat (≥ 43°C), acidic pH (< 6), endogenous lipids <i>N</i>-arachidonoyl dopamine (NADA). Antagonists that block all modes TRPV1 activation elicit hyperthermia. To identify efficacious antagonists do not affect temperature representing multiple pharmacophores were evaluated at...
Objective The aim was to demonstrate that continuous s.c. infusion of a soluble levodopa (LD)/carbidopa (CD) phosphate prodrug combination effectively delivers stable LD exposure via minimally invasive and convenient mode has the potential treat Parkinson's disease (PD) patients who are not well controlled on oral medication. Methods Foslevodopa foscarbidopa were prepared equilibrium solubility chemical stability examined in aqueous media with different values pH. Solutions...
This study describes general methods for the enantioselective syntheses of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates through dirhodium tetracarboxylate-catalysed asymmetric cyclopropanation vinyl heterocycles with aryl- or heteroaryldiazoacetates. The reactions are highly diastereoselective high induction could be achieved using either (R)-pantolactone as a chiral auxiliary tetracarboxylate catalysts. For meta- para-substituted...
The synthesis and characterization of a series selective, orally bioavailable 1-(chroman-4-yl)urea TRPV1 antagonists is described. Whereas first-generation that inhibit all modes activation can elicit hyperthermia, the compounds disclosed herein do not elevate core body temperature in preclinical models only partially block acid TRPV1. Advancing SAR this led to eventual identification (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442, 52), an...
Transient receptor potential vanilloid 3 (TRPV3) is a Ca(2+)- and Na(+)-permeable channel with unique expression pattern. TRPV3 found in both neuronal non-neuronal tissues, including dorsal root ganglia, spinal cord, keratinocytes. Recent studies suggest that may play role inflammation, pain sensation, skin disorders. have been challenging, part due to lack of research tools such as selective antagonists. Herein, we provide the first detailed report on development potent antagonists...
Strategies enabling the construction of indoles and novel polycyclic heterocycles from simple building blocks streamline syntheses in synthetic medicinal chemistry. Herein, we report a C–H functionalization approach to N-alkylindoles proceeding via double, site-selective C(sp3)–H/C(sp2)–H [4 + 1] annulation readily accessed N,N-dialkylanilines. This protocol features hydrogen atom transfer by tuned N-tBu amidyl radical addition sulfonyl diazo coupling partner, which promotes highly homolytic...
Homologations of organic molecules that add a carbon atom to the substrate are useful in drug discovery access compounds with improved properties otherwise present synthetic challenge. Carboxylic acids many bioactive and widely available building blocks for chemical synthesis, yet their direct homologation is unknown. This valuable transformation currently necessitates implementation multistep processes require use carboxylic acid derivatives rather than native substrates, commonly involves...
Formal total syntheses of the naturally occurring deaminated sialic acids KDN (2), a potential oncofetal antigen, and N-acetylneuraminic acid (Neu5Ac, 1), most abundant acid, have been accomplished in 46% 9.3% overall yield, respectively, via novel ketalization/ring-closing metathesis sequence. The rapid introduction all oxygen nitrogen functionality completely stereocontrolled manner exploited rigid 6,8-dioxabicyclo[3.2.1]oct-2-ene template. 2,7-anhydro-KDN derivative 40 served as an...
The regioselective and enantioselective intermolecular sp3 C–H functionalization of silicon-substituted alkanes with aryl diazoacetates was accomplished using the recently developed dirhodium catalyst Rh2(S-TPPTTL)4. These reactions generate a diverse array stereodefined substituted silacycloalkanes high enantioselectivity diastereoselectivity.
We report the development and demonstration of a continuous-flow process for safe formation, extraction, drying aryldiazoacetate 2, which enables direct use in fed-batch dirhodium-catalyzed enantioselective cyclopropanation reaction to provide cyclopropane 4. Designing this with safety as primary objective, we identified appropriate arylsulfonyl hydrazone starting material organic soluble base facilitate Bamford–Stevens diazo-generating flow at 30 °C, well below thermal onset temperature...
Diverse DNA-encoded libraries of complex and novel sp 3 -rich spirocycles were achieved using a versatile operationally simple visible light-mediated intermolecular [2 + 2] cycloaddition.
Formal synthesis of the naturally occurring deaminated sialic acid KDN, a potential oncofetal antigen, has been accomplished in 45% overall yield via novel ketalization/ring-closing metathesis sequence. The rapid introduction all oxygen functionality completely stereocontrolled manner exploited rigid 6,8-dioxabicyclo[3.2.1]oct-2-ene ring system. This general synthetic strategy should provide access to number KDN and analogues.
Synthesis of the northern hemisphere (C1−C16) bryostatin 1, a potent anticancer agent, has been accomplished in 14 steps and 11% overall yield via desymmetrization by ketalization/ring-closing metathesis. A 2,9-dioxabicyclo[3.3.1]nonane template facilitated stereoselective A-ring functionalization, while an efficient hetero-Diels−Alder reaction was used to elaborate B-ring.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of (+)-Didemniserinolipid B: Application a 2-Allyl-4-fluorophenyl Auxiliary for Relay Ring-Closing MetathesisChristopher C. Marvin, Eric A. Voight, Judy M. Suh, Christopher L. Paradise, and Steven D. Burke*View Author Information Department Chemistry, University Wisconsin-Madison,1101 Avenue, Madison, Wisconsin 53706-1322[email protected]Cite this: J. Org. Chem. 2008, 73, 21, 8452–8457Publication Date (Web):September 24, 2008Publication...
Transient receptor potential vanilloid 1 (TRPV1) is a multifunctional ion channel playing important roles in numerous biological processes including the regulation of body temperature. Within distinct and tight chemical space chromanyl ureas TRPV1 ligands were identified that exhibit distinctive pharmacology spectrum thermoregulatory effects ranging from hypothermia to hyperthermia. The ability manipulate these by subtle structural modifications may serve as productive approach drug...
A modular synthesis of didemniserinolipid B is reported. Central to this was the use a ketalization/ring-closing metathesis (K/RCM) strategy establish 6,8-dioxabicyclo[3.2.1]octane core. The C10 axial alcohol established via selective epoxidation, followed by reductive trans-diaxial epoxide opening. serinol and unsaturated ester side chains were introduced Williamson etherification cross metathesis, respectively.
An efficient enantioselective total synthesis of the potent antibiotic GSK966587 was accomplished. Highlights include two innovative Heck reactions, a highly selective zincate base directed ortho-metalation, Sharpless asymmetric epoxidation, and fully convergent final step fragment coupling.
An efficient and convenient synthesis of 2,2,2-trichloroethyl (TCE) aryl- vinyldiazoacetates was achieved by palladium-catalyzed cross-coupling reactions between TCE diazoacetates aryl or vinyl iodides. The broad substrate scope allows for rapid facile formation vinyldiazoacetates, which recently have emerged as versatile reagents rhodium-carbene chemistry.
The room temperature palladium-catalyzed cross-coupling of aromatic and heteroaromatic halides with Reformatsky reagents derived from 1-bromocyclopropanecarboxylates provides an exceptionally mild method for enolate α-arylation. is tolerant a wide range functionalities dramatically shortens many the existing routes to access widely used 1,1-disubstituted cyclopropanecarboxylate derivatives.