A5066173922- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthesis and Biological Evaluation
- HIV/AIDS drug development and treatment
- Asymmetric Synthesis and Catalysis
- HIV Research and Treatment
- Chemical Synthesis and Analysis
- Synthesis and bioactivity of alkaloids
- Synthesis and Reactivity of Heterocycles
- Synthesis and Reactions of Organic Compounds
- Chemical Reaction Mechanisms
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Characterization of Pyrroles
- Synthesis of Indole Derivatives
- Hepatitis C virus research
- Crystallography and molecular interactions
- Chemical synthesis and alkaloids
- Synthesis and biological activity
- Synthetic Organic Chemistry Methods
- Synthesis and Catalytic Reactions
- Crystal structures of chemical compounds
- Advanced Synthetic Organic Chemistry
- Computational Drug Discovery Methods
- Chemical Synthesis and Reactions
- Carbohydrate Chemistry and Synthesis
Lomonosov Moscow State University
2014-2024
A. N. Nesmeyanov Institute of Organoelement Compounds
2020
National Research University Higher School of Economics
2019
Moscow State University
2008-2017
Guanine (G)-rich nucleic acids can fold into G-quadruplex (G4) structures under permissive conditions. Although many RNAs contain sequences that RNA G4s (rG4s) in vitro, their folding and functions vivo are not well understood. In this report, we showed the of putative rG4s human cells rG4 is dynamically regulated stress. By using high-throughput dimethylsulfate (DMS) probing, identified hundreds endogenous stress-induced rG4s, validated them by an pull-down approach. Our results demonstrate...
In our attempt to optimize the lead HIV-1 entry antagonist, NBD-11021, we present in this study rational design and synthesis of 60 new analogues determination their antiviral activity a single-cycle multicycle infection assay derive comprehensive structure-activity relationship (SAR). Two these compounds, NBD-14088 NBD-14107, showed significant improvement compared antagonist against large panel Env-pseudotyped viruses. The X-ray structure similar compound, NBD-14010, confirmed binding mode...
Earlier we reported the discovery and design of NBD-556 their analogs which demonstrated potential as HIV-1 entry inhibitors. However, progress in developing these inhibitors has been stymied by CD4-agonist properties, an unfavorable trait for use drug. Here, demonstrate successful conversion a full (NBD-556) through partial (NBD-09027), to CD4-antagonist (NBD-11021) structure-based modification critical oxalamide midregion, previously thought be intolerant modification. NBD-11021 showed...
The potential of deuterated pharmaceuticals is being widely demonstrated. Here we describe the first trideuteromethylation under radical reaction conditions using dimethyl sulfoxide as a reagent for synthesis labelled heterocycles and trideuteromethylated compounds. A broad scope developed method various scaffolds was
We previously reported a milestone in the optimization of NBD-11021, an HIV-1 gp120 antagonist, by developing new and novel analogue, NBD-14189 (Ref1), which showed antiviral activity against HIV-1HXB2, with half maximal inhibitory concentration 89 nM. However, cytotoxicity remained high, absorption, distribution, metabolism, excretion (ADME) data relatively poor aqueous solubility. To optimize these properties, we replaced phenyl ring compound pyridine synthesized set 48 compounds. One...
The healthy human body contains small amounts of metabolic formaldehyde (FA) that mainly results from methanol oxidation by pectin methylesterase, which is active in a vegetable diet and the gastrointestinal microbiome. With age, ability to maintain low level FA decreases, increases risk Alzheimer's disease dementia. It has been shown 1,2-dithiolane-3-pentanoic acid or alpha lipoic (ALA), naturally occurring dithiol antioxidant cofactor mitochondrial α-ketoacid dehydrogenases, glutathione...
Abstract The pathway by which HIV‐1 enters host cells is a prime target for novel drug discovery because of its critical role in the life cycle HIV‐1. envelope glycoprotein gp120 plays an important initiating virus entry targeting primary cell receptor CD4. We explored substitution bulky molecular groups region I NBD class inhibitors. Previous attempts at substituents that abolished antiviral activity, even though binding site hydrophobic. synthesized series inhibitors containing...
NAPRT, the rate-limiting enzyme of Preiss-Handler NAD biosynthetic pathway, has emerged as a key biomarker for clinical success NAMPT inhibitors in cancer treatment. Previous studies found that high protein levels NAPRT conferred resistance to inhibition several tumor types whereas simultaneous blockade and results marked anti-tumor effects. While research mainly focused on inhibitors, few available (NAPRTi) have low affinity been scarcely characterized. In this work, collection diverse...
Abstract A one‐pot Sonogashira cross‐coupling/5‐ endo ‐ dig cyclization procedure leading to 2‐aryl‐4,5,6,7‐tetrahydroindoles was developed. This short (only two steps from commercially available compounds) sequence avoids harsh conditions and expensive catalysts. Our is highly tolerant a range of functional groups (amino, nitro, carboxy, cyano, hydroxy, bromo). family 21 tetrahydroindoles synthesized on gram scale in good excellent yields, which indicative the general character scalability...
We have developed an efficient and stereoselective route to trans-fused octahydrocyclohepta[b]pyrrol-4(1H)-ones. The key features of our synthesis include the regioselective epoxide ring-opening alkynyl oxiranes a aza-Cope-Mannich reaction. target compounds were prepared in 3-6 steps from commercially available starting materials (61-75% overall yield) with minimal chromatographic purification. devised using Shi epoxidation or (R)-1-phenylethylamine as source chirality.
Herein we suggest an approach to oxygenated bicyclic amino acids based on aza-Cope-Mannich rearrangement. Seven distinct acid scaffolds analogous the natural products were prepared a gram scale with precise control of stereochemistry. Successful implementation our strategy resulted in formal synthesis acetylaranotin.
5-Arylpyrrole-2-carboxylic acids are important key intermediates in the synthesis of HIV-1 entry inhibitors (such as NBD-11021 and NBD-14010). Here we present a general method for some 5-arylpyrrole-2-carboxylic three steps starting from pyrrole. By this method, compounds could be prepared on gram scale without chromatographic purification.
Abstract Asp368 in the HIV‐1 envelope glycoprotein gp120 plays a critical role binding to Arg59 of primary cellular receptor CD4 through forming salt‐bridge initiate entry and infection. The molecules capable interfering with virus host cells are termed entry/attachment inhibitors. Earlier, we designed N‐(2‐amino‐1‐(5‐(hydroxymethyl)‐4‐methylthiazol‐2‐yl)ethyl)‐5‐(4‐chloro‐3‐fluorophenyl)‐1H‐pyrrole‐2‐carboxamide series compounds as inhibitors targeted gp120. Here, report incorporation...
Medicinal chemists are keen to explore tridimensional compounds, especially when it comes small molecules. It has already been stressed that the majority of known drugs tend be flat, whereas natural products more and represent a good source active compounds. 3D metrics have implemented computational descriptors available evaluate prioritize compounds based on their geometry. This is usually done by comparing saturated carbon atoms in molecule with total number its non-hydrogen (the Fsp3...
Abstract Evolutionary potential of viruses can result in outbreaks well‐known and emergence novel ones. Pharmacological methods intervening the reproduction various less popular, but not important are available, as well spectrum antiviral activity for most known compounds. In framework chemical biology paradigm, characterization new compounds allows to extend space provides structure–activity relationships data‐driven drug discovery. Here we present a primary assessment spiro‐annulated...
Matrix metalloproteinases (MMPs) are well-established targets for several pathologies. In particular, MMP-2 and MMP-13 play a prominent role in cancer progression. this study, structure-based screening campaign was applied to prioritize metalloproteinase-oriented fragments. This computational model representative fragment set from the publically available EDASA Scientific compound library. These fragments were prioritized, top-ranking hits tested biological assay validate model. Two...