A5079922034- Chemical Synthesis and Analysis
- Chemical Synthesis and Reactions
- Cancer-related Molecular Pathways
- Advanced Synthetic Organic Chemistry
- Asymmetric Hydrogenation and Catalysis
- Catalytic Cross-Coupling Reactions
- Synthetic Organic Chemistry Methods
- Chemical synthesis and alkaloids
- Asymmetric Synthesis and Catalysis
- Catalytic Alkyne Reactions
- Catalytic C–H Functionalization Methods
- Fluorine in Organic Chemistry
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Synthesis and Catalytic Reactions
- Coordination Chemistry and Organometallics
- Synthesis and Biological Evaluation
- Trypanosoma species research and implications
- Organic Chemistry Cycloaddition Reactions
- Carbon dioxide utilization in catalysis
- Synthesis of β-Lactam Compounds
- Synthesis of heterocyclic compounds
- Cyclopropane Reaction Mechanisms
- Research on Leishmaniasis Studies
Universidade Estadual de Campinas (UNICAMP)
2017-2024
Universidade de São Paulo
2019
Imperial College London
2013-2018
University of California, Irvine
2010-2012
University of Wisconsin–Madison
2008-2009
University of Minnesota
2005
Urbana University
2003
University of Illinois Urbana-Champaign
2002
Yonsei University
2002
A Brønsted acid-catalyzed highly stereoselective arene-ynamide cyclization is described. These reactions constitute a keteniminium variant of Pictet−Spengler cyclizations, leading to efficient synthesis nitrogen heterocycles and related alkaloids. Total syntheses desbromoarborescidines C are illustrated here as first applications this methodology.
Recent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting targeting the transcriptional machinery provides new approaches treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating C-terminal domain (CTD) of RNA polymerase II (PolII) enable initiation. CDK7 additionally regulates activities a number factors, including estrogen receptor (ER)-α. Here we describe new, orally bioavailable inhibitor,...
(−)-Sparteine mediated lithiations of N-Boc-allylic and benzylic amines provide configurationally stable intermediates which on conjugate additions to nitroalkenes highly enantioenriched enecarbamate products in good yields, with high diastereoselectivities. Straightforward transformations these adducts offer general routes substituted 3,4-substituted piperidines, pyrrolidines, 4,5-substituted pyrimidinones. Diastereoselective substitutions intermediate lactams followed by reduction...
A detailed account on chiral secondary amine salt promoted enantioselective intramolecular formal aza-[3 + 3] cycloadditions is described here for the first time. The dependence of enantioselectivity structural feature these amines thoroughly investigated. This study also reveals a very interesting reversal stereochemistry in respective cycloadducts obtained using C(1)- and C(2)-symmetric salts. In addition, influence solvents, counteranions, temperatures described, unified mechanistic model...
A virtual screening conducted with nearly 4 000 compounds from lead-like and fragment-like subsets enabled the identification of a small-molecule inhibitor (1) Trypanosoma cruzi cruzain enzyme, validated drug target for Chagas disease. Subsequent comprehensive structure-based design structure-activity relationship studies led to discovery carbamoyl imidazoles as potent, reversible, competitive inhibitors. The most potent imidazole (45) exhibited high affinity Ki value 20 nM, presenting both...
Lepadiformine A, B, and C were synthesized in an enantiomerically pure form using a reductive cyclization strategy. N-Boc α-amino nitriles deprotonated alkylated with dibromides to afford the first ring. The products manipulated introduce phosphate leaving groups, subsequent lithiation followed by intramolecular alkylation formed second ring high stereoselectivity. third was displacement of mesylate deprotected amine. A B contain hydroxymethyl group adjacent This appendage introduced...
Reductive lithiation of N-Boc α-amino nitriles generated alkyllithium reagents with unexpected selectivity. The intermediate radical prefers to align the nitrogen lone pair, and this interaction leads an A1,3-strain effect that biases conformation radical. In cyclohexane rings α-substituents net is inversion configuration on reductive lithiation. presence a tethered electrophile cyclizes produce spiro compound, again configuration. overall result retention in cyclization reaction. same...
Cruzain, the main cysteine protease of Trypanosoma cruzi, plays key roles in all stages parasite's life cycle, including nutrition acquisition, differentiation, evasion host immune system, and invasion cells. Thus, inhibition this validated target may lead to development novel drugs for treatment Chagas disease. In study, a multiparameter optimization (MPO) approach, molecular modeling, structure-activity relationships (SARs) were employed identification new benzimidazole derivatives as...
ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTTotal Synthesis of (+)-Lepadin FGang Li, Richard P. Hsung*, Brian W. Slafer, and Irina K. SagamanovaView Author Information Division Pharmaceutical Sciences Department Chemistry, 777 Highland Avenue, University Wisconsin, Madison, Wisconsin 53705[email protected]Cite this: Org. Lett. 2008, 10, 21, 4991–4994Publication Date (Web):September 27, 2008Publication History Received3 September 2008Published online27 inissue 6 November...
Aim: Chagas disease is endemic in Latin America and no effective treatment available. Efforts drug research have focused on several enzymes from Trypanosoma cruzi, among which cruzain a validated pharmacological target. Methodology: Chemometric analyses were performed the data set using hologram quantitative structure–activity relationship, comparative molecular field analysis similarity index methods. Docking simulations executed crystallographic structure of complex with benzimidazole...
Details in developing a stereodivergent approach to the lepadin family and establishing an entry both C2,8a-syn C2,8a-anti relative stereochemical manifolds through common intermediate are described here. This works paves foundation for constructing all members of family, which consists three subsets based on array interesting configurations. These efforts underline prominence aza-[3+3] annulation as unified strategy alkaloid synthesis.
Chagas disease (CD) is a parasitic neglected tropical (NTD) caused by the protozoan
Abstract For see ChemInform in Full Text.
Abstract For see ChemInform in Full Text.
Abstract Cyclin-dependent kinases (CDKs) form complexes with partner cyclins to regulate cell cycle progression and transcription. CDK1, CDK2, CDK4 CDK6 all CDK8 CDK9 are regulators of CDK7 is a unique member this family because it can the CDKs as part CDK-activating kinase (CAK) also transcription in conjunction TFIIH factor by phosphorylating COOH-terminal domain RNA polymerase II (Pol CTD). A hallmark cancer deregulated many cancers have abnormal CDK activity which makes good target for...
Abstract Cyclin dependent kinases (CDK) function as either regulators of cell cycle progression or transcription. CDK7 is unique from other CDKs because it has a dual role in the regulation and transcription making desirable target for drug development. It forms complex with H MAT1 to form CDK-activating kinase (CAK) that regulates CDK1, CDK2, CDK4 CDK6, which are important progression. The CAK can also act transcriptional regulator part TFIIH factor by phosphorylating COOH-terminal domain...
<p>Pharmacokinetic determination of ICEC0942 plasma and tumor concentrations at different doses over time.</p>
<p>Oral administration of ICEC0942 inhibits cyclin-dependent kinase substrate phosphorylation in mouse peripheral blood mononuclear cells.</p>
<p>Figure legends for supplementary Figures</p>
<p>Cell Cycle analysis of MCF7 cells treated with ICEC0942.</p>
<p>Combinatorial inhibition of breast cancer cells with a combination ICEC0942 and anti-estrogens.</p>
<p>ADME analysis, oral bioavailability and distribution of ICEC0942.</p>
<p>Analysis of ICEC0942 treatment MCF7 cells.</p>
<p>In vitro kinase assays demonstrate selectivity of ICEC0942 for CDK7.</p>
<div>Abstract<p>Recent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting targeting the transcriptional machinery provides new approaches treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating C-terminal domain (CTD) of RNA polymerase II (PolII) enable initiation. CDK7 additionally regulates activities a number factors, including estrogen receptor (ER)-α. Here we describe new,...