Saccharin salts of biologically active hydrazone derivatives

2015 ◽  
Vol 39 (11) ◽  
pp. 8614-8622 ◽  
Author(s):  
Artem O. Surov ◽  
Alexander P. Voronin ◽  
Anna A. Simagina ◽  
Andrei V. Churakov ◽  
Sophia Y. Skachilova ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Biologically Active ◽  
Formation Thermodynamics

Crystal structures, solubility and formation thermodynamics of saccharin salts with biologically active hydrazone derivatives were investigated.

scholarly journals Novel drug–drug cocrystals of carbamazepine with para-aminosalicylic acid: screening, crystal structures and comparative study of carbamazepine cocrystal formation thermodynamics

CrystEngComm ◽  
2017 ◽  
Vol 19 (30) ◽  
pp. 4273-4286 ◽  
Author(s):  
Ksenia V. Drozd ◽  
Alex N. Manin ◽  
Andrei V. Churakov ◽  
German L. Perlovich
Keyword(s):  
Comparative Study ◽  
Crystal Structures ◽  
Anticonvulsant Drug ◽  
Aminosalicylic Acid ◽  
Antituberculous Drug ◽  
Novel Drug ◽  
Formation Thermodynamics

The cocrystal formation of the anticonvulsant drug carbamazepine (CBZ) with para-aminosalicylic acid (PASA, antituberculous drug) has been studied by varying methods.

scholarly journals A Simple and Mild Microwave-Based Synthesis of Novel Functionalized Benzofulvenes

SynOpen ◽  
2018 ◽  
Vol 02 (03) ◽  
pp. 0256-0262
Author(s):  
Adam Glass ◽  
Katherine Caspary ◽  
Cole Fisher ◽  
Connor Whyte ◽  
James Okubo ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Microwave Heating ◽  
Good Yield ◽  
Optoelectronic Devices ◽  
Biologically Active ◽  
Synthetic Method ◽  
Polymer Precursors ◽  
Coupling Techniques

Benzofulvenes and their derivatives are useful molecular entities having applications as biologically active molecules, polymer precursors, and optoelectronic devices. We have developed a simple and mild synthetic method for the formulation of a variety of these interesting compounds. Using carbonyl coupling techniques combined with microwave heating, a wide variety of functionalized benzofulvenes can be accessed rapidly in good yield. Furthermore, we have obtained five crystal structures further expanding a limited number of benzofulvene structures available.

Conformational study of the 3,6-dihydro-2H-1,4-oxazin-2-one fragment in 8-tert-butyl-7-methoxy-8-methyl-9-oxa-6-azaspiro[4.5]decane-2,10-dione stereoisomers

2017 ◽  
Vol 73 (7) ◽  
pp. 556-562
Author(s):  
Ewa Żesławska ◽  
Anna Jakubowska ◽  
Wojciech Nitek
Keyword(s):  
Amino Acids ◽  
Crystal Structures ◽  
Stereoselective Synthesis ◽  
Biologically Active ◽  
Asymmetric Unit ◽  
Conformational Study ◽  
X Ray Diffraction ◽  
X Ray ◽  
Natural Amino Acids ◽  
Heterocyclic Moiety

Unnatural cyclic α-amino acids play an important role in the search for biologically active compounds and macromolecules. Enantiomers of natural amino acids with a D configuration are not naturally encoded, but can be chemically synthesized. The crystal structures of two enantiomers obtained by a method of stereoselective synthesis, namely (5R,8S)-8-tert-butyl-7-methoxy-8-methyl-9-oxa-6-azaspiro[4.5]decane-2,10-dione, (1), and (5S,8R)-8-tert-butyl-7-methoxy-8-methyl-9-oxa-6-azaspiro[4.5]decane-2,10-dione, (2), both C14H21NO4, were determined by X-ray diffraction. Both enantiomers crystallize isostructurally in the space group P21, with one molecule in the asymmetric unit and with the same packing motif. The crystal structures are stabilized by C—H...O hydrogen bonds, resulting in the formation of chains along the [100] and [010] directions. The conformation of the 3,6-dihydro-2H-1,4-oxazin-2-one fragment was compared with other crystal structures possessing this heterocyclic moiety. The comparison showed that the title compounds are not exceptional among structures containing the 3,6-dihydro-2H-1,4-oxazin-2-one fragment. The planar moiety was more frequently observed in derivatives in which this fragment was not condensed with other rings.

A combined experimental and theoretical study of miconazole salts and cocrystals: crystal structures, DFT computations, formation thermodynamics and solubility improvement

2021 ◽  
Author(s):  
Ksenia V. Drozd ◽  
Alex N. Manin ◽  
Alexander P. Voronin ◽  
Denis Boycov ◽  
Churakov Andrei ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Theoretical Study ◽  
Molecular Crystals ◽  
Dicarboxylic Acids ◽  
Antifungal Drug ◽  
Crystal Forms ◽  
Dft Computations ◽  
Solubility Improvement ◽  
Aliphatic Dicarboxylic Acids ◽  
Formation Thermodynamics

Experimental and theoretical screening of multi-component crystal forms of miconazole (MCL), an antifungal drug, with ten aliphatic dicarboxylic acids was performed. Seven multi-component molecular crystals were isolated and identified by...

scholarly journals Supramolecular organization of complexes of aryl hydrazones with SnCl3and SnCl4

2014 ◽  
Vol 70 (a1) ◽  
pp. C657-C657
Author(s):  
Alexander Korlyukov ◽  
Anna Vologzhanina ◽  
Evgenia Voronova ◽  
Natalia Shmatkova ◽  
Inna Seifullina
Keyword(s):  
Crystal Structures ◽  
Electron Density ◽  
Intermolecular Interactions ◽  
Active Species ◽  
Biologically Active ◽  
Supramolecular Organization ◽  
Halogen Bonds ◽  
Covalent Interaction ◽  
Theoretical Approaches ◽  
Density Analysis

Chelate complexes of main group metals with N,O-chelating Schiff Base ligands have been reported as perspective models for biologically active species. The derivatives of aryl hydrazones are among the most widely used ligands of such type. In our study, crystal structures of aryl hydrazones with SnCl3and SnCl4are discussed: the presence of aromatic fragments, amine groups and chlorine atoms therein are responsible for the coexistence of strong hydrogen and halogen bonds as well as stacking and Cl...π interactions. Interplay between these types of interactions and their role in stabilization of crystal structures is the subject of particular interest. We studied all these aspects in complexes of aryl hydrazones using different theoretical approaches: those based on Stockholder partitioning, molecular electrostatic potential, non-covalent interaction index, AIM theory – together with Espinosa-Mollins-Lecomte correlation to estimate the energy of all intermolecular interactions in crystals by means of electron density analysis from periodic quantum chemical calculations (VASP code). Our results showed that the presence of intermolecular interactions led to a noticeable redistribution of electron density in crystal as compared to an isolated molecule. Although Cl...π, stacking interactions and halogen bonds are numerous in the crystals of these complexes, their contribution to the energy of their crystal lattice does not exceed 30%. The work was supported by Council of the President of the Russian Federation (grant MD-3589.2014.3).

scholarly journals Structure of Biologically Active Benzoxazoles: Crystallography and DFT Studies

2021 ◽  
Vol 68 (1) ◽  
pp. 144-150
Author(s):  
Una Glamočlija ◽  
Selma Špirtović-Halilović ◽  
Mirsada Salihović ◽  
Iztok Turel ◽  
Jakob Kljun ◽  
...  
Keyword(s):  
Single Crystal ◽  
Crystal Structures ◽  
Energy Gap ◽  
Molecular Geometry ◽  
Biologically Active ◽  
Basis Set ◽  
Single Crystal Diffraction ◽  
X Ray ◽  
Experimental Values ◽  
Homo Lumo

Using X-ray single crystal diffraction, the crystal structures of biologically active benzoxazole derivatives were determined. DFT calculation was performed with standard 6-31G*(d), 6-31G** and 6-31+G* basis set to analyze the molecular geometry and compare with experimentally obtained X-ray crystal data of compounds. The calculated HOMO-LUMO energy gap in compound 2 (2-(2-hydroxynaphtalen-1-yl)-4-methyl-7-isopropyl-1,3-benzoxazol-5-ol) is 3.80 eV and this small gap value indicates that compound 2 is chemically more reactive compared to compounds 1 (4-methyl-2-phenyl-7-isopropyl-1,3-benzoxazol-5-ol) and 3 (2-(4-chlorophenyl)-4-methyl-7-isopropyl- 1,3-benzoxazol-5-ol). The crystal structures are stabilized by both intra- and intermolecular hydrogen bonds in which an intermolecular O–H⋅⋅⋅N hydrogen bond generates N3 and O7 chain motif in compounds 1, 2, and 3, respectively. The calculated bond lengths and bond angles of all three compounds are remarkably close to the experimental values obtained by X-ray single crystal diffraction.

scholarly journals Crystal structures of the σ2 receptor template large-library docking for selective chemotypes active in vivo

2021 ◽  
Author(s):  
Assaf Alon ◽  
Jiankun Lyu ◽  
Joao M. Braz ◽  
Tia A. Tummino ◽  
Veronica Craik ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Crystal Structures ◽  
Large Scale ◽  
Protein Structures ◽  
Biologically Active ◽  
Drug Candidate ◽  
Binding Affinities ◽  
Injury Model ◽  
Selective Ligand

The σ2 receptor is a poorly understood transmembrane receptor that has attracted intense interest in many areas of biology including cancer imaging, Alzheimer's disease, schizophrenia, and neuropathic pain. However, little is known regarding the molecular details of the receptor, and few highly selective ligands are available. Here, we report the crystal structure of the σ2 receptor in complex with the clinical drug candidate roluperidone and the probe compound PB28. These structures, in turn, templated a large-scale docking screen of 490 million make-on-demand molecules. Of these, 484 compounds were synthesized and tested, prioritizing not only high-ranking docked molecules, but also those with mediocre and poor scores. Overall, 127 compounds with binding affinities superior to 1 μM were identified, all in new chemotypes, 31 of which had affinities superior to 50 nM. Intriguingly, hit rate fell smoothly and monotonically with docking score. Seeking to develop selective and biologically active probe molecules, we optimized three of the original docking hits for potency and for selectivity, achieving affinities in the 3 to 48 nM range and to up to 250-fold selectivity vs. the σ1 receptor. Crystal structures of the newly discovered ligands bound to the σ2 receptor were subsequently determined, confirming the docked poses. To investigate the contribution of the σ2 receptor in pain processing, and to distinguish it from the contribution of the σ1 receptor, two potent σ2-selective and one potent σ1/σ2 non-selective ligand were tested for efficacy in a mouse model of neuropathic pain. All three ligands demonstrated time-dependent decreases in mechanical hypersensitivity in the spared nerve injury model, supporting a role for the σ2 receptor in nociception, and a possible role for σ1/σ2 polypharmacology. This study illustrates the opportunities for rapid discovery of in vivo active and selective probes to study under-explored areas of biology using structure-based screens of diverse, ultra-large libraries following the elucidation of protein structures.

scholarly journals Serotonin in different compounds: crystallographic and computational insight

2014 ◽  
Vol 70 (a1) ◽  
pp. C918-C918
Author(s):  
Denis Rychkov ◽  
Elena Boldyreva ◽  
Viktor Kovalskii ◽  
Steven Hunter ◽  
Colin Pulham ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Molecular Conformation ◽  
Chemical Properties ◽  
Molecular Geometry ◽  
Point Of View ◽  
Biologically Active ◽  
Theoretical Point ◽  
Chemical Research ◽  
Stable Conformation ◽  
Crystalline Environment

Biologically active substances are in the focus of pharmaceutical and chemical research. Serotonin, one of the most common neurotransmitters, is widely studied in relation to its effect on humans from cellular to neurological levels. Although serotonin plays a key role in some biological processes, its chemistry and crystallography are not sufficiently understood. The aim of the present study was to crystallize serotonin adipate and creatinine sulfate monohydrate, determine their crystal structures, and analyze them in a comparison with other previously known serotonin crystal structures. Special attention was paid to the interrelation between the molecular conformation and crystalline environment. This issue was addressed using crystallographic and computational chemistry (DFT-D, MD) approaches. In our research was shown that the crystal structure of the creatinine sulfate complex significantly differs from what was previously determined. The conformation of serotonin in the new structure differs from serotonin conformations in all other known complexes, as well as from the most stable conformation, predicted by the adiabatic conformational analysis using quantum chemical calculations (DFT, MP) in different phases. This work has explicitly shown the influence of different interactions on serotonin molecular conformation in the crystalline state, described from a crystallographic and theoretical point of view. It has been previously demonstrated that salt formation in the presence of different anions produces variation in pharmacological, therapeutic and physic-chemical properties. This study has shown that alterations of the anion affects the molecular geometry of the bioactive substance and invite further investigation to rationalize the geometry changes. The work was supported by the RFBR Grants No.14-03-31866, 13-03-92704, Russian Ministry of Science and Education and RAS, Siberian Supercomputer Center SB RAS Integration Grant No.130, Edinburgh Compute and Data Facility

Novel cocrystals of the potent 1,2,4-thiadiazole-based neuroprotector with carboxylic acids: virtual screening, crystal structures and solubility performance

2021 ◽  
Vol 45 (6) ◽  
pp. 3034-3047
Author(s):  
Artem O. Surov ◽  
Alexander P. Voronin ◽  
Nikita A. Vasilev ◽  
Andrey B. Ilyukhin ◽  
German L. Perlovich
Keyword(s):  
Virtual Screening ◽  
Crystal Structures ◽  
Carboxylic Acids ◽  
Biologically Active ◽  
Thiadiazole Derivative ◽  
Hydroxybenzoic Acids ◽  
Cocrystal Screening

Five new multicomponent solid forms of the biologically active 1,2,4-thiadiazole derivative (TDZH) with dicarboxylic and hydroxybenzoic acids have been discovered by combined virtual/experimental cocrystal screening.

Sign in / Sign up

Export Citation Format

Share Document