Dmitrii Kalinin

Dmitrii Kalinin
University of Münster | WWU · Institute of Pharmaceutical and Medicinal Chemistry

PhD in Medicinal Chemistry

About

28
Publications
4,733
Reads
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288
Citations
Additional affiliations
May 2017 - present
University of Southern Denmark
Position
  • PostDoc Position
Description
  • Development of methods for synthesis of receptor ligands
October 2013 - October 2016
University of Münster
Position
  • PhD Student
February 2011 - November 2011
Curtin University
Position
  • Research Associate

Publications

Publications (28)
Article
We herein report the conventional and microscale parallel synthesis of selective inhibitors of human blood coagulation factor XIIa and thrombin exhibiting a 1,2,4-triazol-5-amine scaffold. Structural variations of this scaffold allowed identifying derivative 21i, a potent 29 nM inhibitor of FXIIa, with improved selectivity over other tested serine...
Cover Page
Full-text available
The Front Cover shows the X‐ray crystal structure of the novel antiparasitic target Schistosoma mansoni histone deacetylase 8 (smHDAC8) in complex with our developed triazole‐based inhibitor. The inhibitor, whose structural formula is displayed top right, is the result of chemical modifications of the triazole‐based hit compound (top left), which w...
Article
Metal-dependent histone deacetylases (HDACs) are key epigenetic regulators that represent promising therapeutic targets for the treatment of numerous human diseases. Yet, the currently FDA-approved HDAC inhibitors non-specifically target at least several of the eleven structurally similar but functionally different HDAC isozymes, which hampers thei...
Article
As dysregulation of matrix metalloproteinase (MMP) activity is associated with a wide range of pathophysiological processes like cancer, atherosclerosis, and arthritis, MMPs represent a valuable target for the development of new therapeutics and diagnostic tools. We herein present the chiral pool syntheses, in vitro evaluation and SAR studies of a...
Article
The structure of the known Penicillium aurantiogriseum-derived secondary metabolite auranthine was refined using a combination of synthetic, spectroscopic, and X-ray diffractometric approaches. Thus, auranthine was shown to be a fused quinazolino benzodiazepinedione (2) bearing an acyclic aliphatic nitrile moiety, thereby significantly differing fr...
Preprint
Background. Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy commonly associated with Kasabach-Merritt phenomenon (KMP) that includes thrombocytopenia and coagulation dysfunction. Platelet receptor CLEC-2 -tumor cell podoplanin interaction is considered the key mechanism of thrombocytopenia in KMP, however, the effect of lo...
Preprint
Background. Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy commonly associated with Kasabach-Merritt phenomenon (KMP) that includes thrombocytopenia and coagulation dysfunction. Platelet receptor CLEC-2 -tumor cell podoplanin interaction is considered the key mechanism of thrombocytopenia in KMP, however, the effect of lo...
Article
Full-text available
The Cover Feature illustrates a microscale parallel synthetic approach leading to novel N-acylated aminotriazoles having anticoagulant properties. The bottom part of the picture demonstrates the life-threatening thrombus, whereas the upper part shows the developed covalent inhibitor of the blood coagulation factor XIIa. Inhibitors of this class tra...
Article
Full-text available
We herein report a microscale parallel synthetic approach allowing for fast access to libraries of N-acylated aminotriazoles and screening of their inhibitory activity against FXIIa and thrombin, which are targets for antithrombotic drugs. This approach in combination with the post-screening structure optimization yielded a potent 7 nM inhibitor of...
Article
Full-text available
Introduction : Blood coagulation factor XII (FXII) is an emerging and potentially safe drug target, which dysregulation is associated with thrombosis, hereditary angioedema, and (neuro)inflammation. At the same time, FXII-deficiency is practically asymptomatic. Industrial and academic institutions have developed a number of potential therapeutic ag...
Article
Full-text available
Schistosomiasis is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma , which affects over 200 million people worldwide and leads to at least 300,000 deaths every year. In this study, initial screening revealed the triazole‐based hydroxamate 2b exhibiting potent inhibitory activity toward the novel antiparasitic tar...
Article
The Zn2+-dependent deacetylase LpxC is an essential enzyme in Gram-negative bacteria, which has been validated as antibacterial drug target. Herein we report the chiral-pool synthesis of novel d- and l-proline-derived 3,4-dihydroxypyrrolidine hydroxamates and compare their antibacterial and LpxC inhibitory activities with the ones of 4-monosubstitu...
Article
Full-text available
Neuroinflammatory disorders, such as multiple sclerosis (MS) or experimental autoimmune encephalomyelitis (EAE), an established mouse model mimicking part of the human pathology, are characterized by inflammatory infiltrates containing T helper 1 (TH1) and TH17 cells, which cause demyelination and neurodegeneration. Disease onset and perpetuation a...
Article
In order to replace the 4-benzylpiperidine scaffold of potent GluN2B antagonists by fluorinated structural elements, novel fluorinated -phenylalkylamines and one -butyraldehyde were synthesized. These building blocks were introduced in benzoxazol-2-one, indole, tetrahydro-1H-3-benzazepine and tetrahydro-5H-benzo[7]annulen-7-amine scaffolds. This s...
Article
Full-text available
Introduction: The Zn(2+)-dependent deacetylase LpxC is an essential enzyme of lipid A biosynthesis in Gram-negative bacteria and a promising target for the development of antibiotics selectively combating Gram-negative pathogens. Researchers from industry and academia have synthesized structurally diverse LpxC inhibitors, exhibiting different LpxC...
Article
Full-text available
The bacterial enzyme UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC), catalyzing the first committed step of lipid A biosynthesis, represents a promising target in the development of novel antibiotics against Gram-negative bacteria. Structure, catalytic reaction mechanism and regulation of the Zn2+-dependent metalloamidase h...
Article
Full-text available
A new, efficient, catalyst-free, one-pot, three-component method for the synthesis of 2-amino-substituted 7-amino-1,2,4-triazolo[1,5-a][1,3,5]triazines using 3,5-diamino-1,2,4-triazoles, cyanamide, and triethyl orthoformate is developed. The reaction proceeds smoothly under microwave-assisted heating. Advantages of the method include using easily a...
Article
Context: Verbascum nigrum L. (Scrophulariaceae) is a perennial plant used in folk medicine for the treatment of kidney diseases due to its presumable diuretic properties. Objective: We investigated the diuretic activity and toxicity of extracts from different parts of V. nigrum and identified a group of compounds responsible for the biological e...
Article
Full-text available
A novel multicomponent strategy for the efficient synthesis of 5-aza-adenines was developed. 5-Aza-adenines were prepared in a one-pot fashion from 5-amino-1,2,4-triazoles, cyanamide and triethyl orthoformate under microwave irradiation. The operational simplicity, efficiency and accessibility of this method make it highly attractive for the genera...
Article
The reaction of azoles (I) with trichloroacetonitrile (II) proceeds smoothly and regioselectively at the primary amino group of (I) to yield the trichloroacetamidines (III).
Article
Full-text available
The amino substituted triazine ring was annelated to aminoazoles using a new effective synthetic procedure. The method of preparation involved initial formation of azolylformamidines in the reaction of aminoazoles with N,N-dimethylformamide dimethyl acetal followed by the triazine ring closure with cyanamide affording therefore fused aminotriazines...
Article
Full-text available
The triazine ring bearing a trichloromethyl group was annelated to various aminoazoles using a new effective synthetic procedure. The method of preparation involved initial formation of trichloroacetamidines in the reaction of aminoazoles with trichloroacetonitrile followed by the triazine ring closure with triethyl orthoformate affording therefore...
Article
Full-text available
Het)arylamidoguanidines were synthesized from corresponding hydrazides and S-methyl isothiourea. They were screened in vitro for anticoagulant activity using whole canine blood. The most active compounds, namely 4-methylbenzamidoguanidine and nicotinamidoguanidine were also tested on platelet free plasma. No effect was observed for these compounds...

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Projects

Projects (3)
Project
To develop new practical methods for the synthesis of N-heterocyclic compounds under controlled microwave irradiation.
Project
Synthesis of new amino acid derivatives. Evaluation of their ability to inhibit bacterial LpxC, human MMP, and parasitic HDAC. In vivo application for positron emission tomography.