A5056878608- Synthetic Organic Chemistry Methods
- Estrogen and related hormone effects
- Chemical Synthesis and Analysis
- Steroid Chemistry and Biochemistry
- Click Chemistry and Applications
- Marine Sponges and Natural Products
- Innovations in Medical Education
- Carbohydrate Chemistry and Synthesis
- Asymmetric Synthesis and Catalysis
- Hedgehog Signaling Pathway Studies
- Hormonal Regulation and Hypertension
- Epigenetics and DNA Methylation
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Health Sciences Research and Education
- Microbial Natural Products and Biosynthesis
- Indigenous Studies and Ecology
- Healthcare professionals’ stress and burnout
- Interprofessional Education and Collaboration
- Tryptophan and brain disorders
- Catalytic Alkyne Reactions
- Catalytic Cross-Coupling Reactions
- Cyclopropane Reaction Mechanisms
- Arctic and Russian Policy Studies
FogPharma (United States)
2023
Fédération des Maisons D'Hébergement pour Femmes
2023
Business Development Bank of Canada
2022
Tesaro (United States)
2018-2021
Creative Commons
2021
Université de Montréal
1989-2020
Infinity Pharmaceuticals (United States)
2007-2016
Boehringer Ingelheim (Canada)
2012-2013
Alberta Glycomics Centre
2013
University of Alberta
2012-2013
Recent evidence suggests that blocking aberrant hedgehog pathway signaling may be a promising therapeutic strategy for the treatment of several types cancer. Cyclopamine, plant Veratrum alkaloid, is natural product antagonist pathway. In previous report, seven-membered D-ring semisynthetic analogue cyclopamine, IPI-269609 (2), was shown to have greater acid stability and better aqueous solubility compared cyclopamine. Further modifications A-ring system generated three series analogues with...
A concise and convergent total synthesis of the highly cytotoxic marine natural products iejimalide A−D (1−4) is reported, which relies on an effective ring-closing metathesis (RCM) reaction a cyclization precursor containing no less than 10 double bonds. Because exceptional sensitivity this polyunsaturated intermediate its immediate precursors toward acid, base, even gentle warming, assembly process hinged upon judicious choice protecting groups careful optimization all individual...
Optimization of isoquinolinone PI3K inhibitors led to the discovery a potent inhibitor PI3K-γ (26 or IPI-549) with >100-fold selectivity over other lipid and protein kinases. IPI-549 demonstrates favorable pharmacokinetic properties robust inhibition mediated neutrophil migration in vivo is currently Phase 1 clinical evaluation subjects advanced solid tumors.
ABSTRACT The emergence of resistance to existing classes antiretroviral drugs necessitates finding new HIV-1 targets for drug discovery. viral capsid (CA) protein represents one such potential target. CA is sufficient form mature capsids in vitro , and extensive structure-function mutational analyses have shown that the proper assembly, morphology, stability core are essential infectivity virions. Here we describe development an assembly assay based on association CA-NC subunits immobilized...
The combination of catalytic amounts [Pd(PPh3)4], copper thiophene-2-carboxylate (CuTC) and [Ph2PO2][NBu4] allowed a series exigent Stille–Migita reactions to be performed with high yields; as the protocol is fluoride free, variety O-silyl C-silyl groups remained intact.
Herein is reported the synthesis of a novel class hedgehog antagonists derived from cyclopamine. The acid sensitive D-ring cyclopamine was homologated utilizing sequence chemoselective cyclopropanation and stereoselective acid-catalyzed rearrangement. Further modification A/B-ring homoallylic alcohol to conjugated ketone led discovery new analogues with improved pharmaceutical properties in vitro potency (EC 50) ranging 10 1000 nM.
Misregulation of protein translation plays a critical role in human cancer pathogenesis at many levels. Silvestrol, cyclopenta[b]benzofuran natural product, blocks the initiation step by interfering with assembly eIF4F complex. Silvestrol has complex chemical structure whose functional group requirements have not been systematically investigated. Moreover, silvestrol limited development potential due to poor druglike properties. Herein, we sought develop practical synthesis key intermediates...
This study evaluated an inference-based approach (IBA) to the treatment of obsessive-compulsive disorder (OCD) by comparing its efficacy with a based on cognitive appraisal model (CAM) and exposure response prevention (ERP). IBA considers initial intrusions in OCD (e.g. "Maybe door is open", "My hands could be dirty") as idiosyncratic inferences about possible states affairs arrived at through inductive reasoning. In such primary represent starting point obsessional doubt, reasoning...
Abstract For see ChemInform in Full Text.
The structure and absolute configuration of the marine antithrombotic product dysinosin A was confirmed by total synthesis. strategy involved disconnections to three subunits, which two were synthesized from readily available l-glutamic acid, d-leucine, d-mannitol. Grubbs olefin metathesis carbocyclization reaction utilized prepare intermediates.
Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD type 1) catalyzes the final step in synthesis of active estrogens that stimulate proliferation breast cancer cells. Based on initial premise to make use binding energies both substrate and cofactor sites, molecular modeling starting from enzyme structure, several estradiol-adenosine hybrids were designed synthesized. Among these hybrids, EM-1745 with a linker 8-CH2 groups is proved be best competitive inhibitor Ki 3.0 +/- 0.8...
Arctic communities are recently reporting warmer and shorter winters, which have implications for the ice season and, consequently, on access to local territories resources by members of these communities. These climatic shifts resulting in increased risks travel during winter associated with less stable thinner ice. An integrated community-based monitoring (ICBM) program was developed Nunavik generate adaptation tools support safe land enhance adaptive capacity through participation...
Metathesis to the rescue: Although counterintuitive at first sight, application of ring-closing metathesis (RCM) a cyclization precursor containing 10 double bonds has led selective and high-yielding formation macrocyclic core iejimalide B, potent cytotoxic agent marine origin. In contrast, macrolactonization approach failed afford this intricate target.
Dichlorocyclopropanation of 2-amino-1,3-dienes affords 1-alkenyl-1-amino-2,2-dichlorocyclopropanes which undergo silver-assisted 2-π electrocyclic opening to furnish 3-aminopentadienyl cations. Nazarov-type cyclization these intermediates leads cyclopentenone iminium salts, provide allylic amines upon reduction. This process, the imino version traditional Nazarov reaction, can also be combined with an interrupted domino process give polycyclic amines.
The steroidogenic enzyme type 1 17β-hydroxysteroid dehydrogenase (17β-HSD) is involved in the synthesis of estradiol (E2), a hormone well-known to stimulate growth estrogen-sensitive tumors. To obtain compounds able control E2 formation, two moieties were linked with methylene side chain: an adenosine moiety for interacting cofactor-binding site and substrate-binding site. When tested as inhibitors 17β-HSD, hybrid inhibited reductive activity (E1 into E2) IC50 values ranging from 52 1000 nM....
Limitations of models in total synthesis are illustrated by a study towards the potent cytotoxic macrolide iejimalide B. Although Yamaguchi protocol allowed for esterification elaborate segments, attempted macrolactonization seco acid met with failure (see scheme, Boc= tert-butyloxycarbonyl). The assembly involves some most advanced applications Julia olefination known to date.