Spacer conformation in biologically active molecules. Part 1. Structure and conformational preferences of 2-substituted benzoxazoles (original) (raw)
Related papers
Structure of Biologically Active Benzoxazoles: Crystallography and DFT Studies
Acta Chimica Slovenica, 2021
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 valu...
Journal of Chemical Crystallography, 2011
Molecular and crystal structures of two thioamide derivatives of thiazole were analysed based on X-ray diffraction data and results obtained from quantum chemistry (QC) and molecular mechanics (MM) calculations. It was found that within the thiazole rings, the S1-C2 bond appeared to be more affected by the action of two-substituents rather than the C2-N3 bonds. The ab initio calculations showed that the C2-C6 bond connecting the thioamide group with thiazole is shortened when both the systems are coplanar, but a conjugation is relatively weak and does not enforce such conformation. The QC and MM calculations indicated that the particular parts of the thioamide group may exist in two conformations. However, relatively high energy barrier excluded the possibility of change of one conformation into the other by simple rotation around the C2-C6 or C6-N8 bonds. Moreover, the MM calculations explained that steric hindrance is not the main reason of energy barrier for suggested rotations. The observed cis-trans conformation is stabilised by intramolecular hydrogen bonds. ᭧
Crystals, 2021
Two polymorphic forms of a conformationally flexible molecule, 5-[(Diphenylphosphoryl)methyl]-4-(prop-2-en-1-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione, were obtained by crystallization and characterized by X-ray diffraction analysis and differential scanning calorimetry. The relative stability of polymorphic forms was estimated with DFT calculations of crystal structures and isolated molecules. It turns out, that in the first more dense polymorph with higher cohesion energy and crystal lattice energy, the molecule adopts an energetically unfavorable conformation, and forms dimers with lower H-bond strength, as compared to the second polymorph. On the other hand, in the second polymorph, the molecule adopts almost the lowest-energy conformation and forms infinite chains via strong H-bonds. The first form that seems to be more thermodynamically stable at room temperature transforms into the second form via two endothermic phase transitions; the apparent irreversibility of the transit...
Chemistry and Pharmacological Exploration of Benzoxazole Derivatives
https://www.ijrrjournal.com/IJRR\_Vol.9\_Issue.12\_Dec2022/IJRR-Abstract37.html, 2022
Benzoxazole is one of the most prominent heterocyclic structures and is found in an extensive range of biologically active compounds. It is one of the often occurring heterocyclic nitrogen-containing moieties that perform as the primary active elements of pharmaceutical compounds. It can be viewed as isosteres of the naturally occurring guanine and adenine nucleic bases since they interact effectively with the polymeric components of biological systems. A wide range of biological features, including analgesic, antibacterial, anti-inflammatory, anti-hyperglycemic, anticancer, antiviral, antifungal, antileishmanial, and antitubercular activities, they are significantly influenced by heterocyclic compounds with a benzoxazole nucleus.
BENZOXAZOLE: THE MOLECULE OF DIVERSE PHARMACOLOGICAL IMPORTANCE
International Journal of Pharmacy and Pharmaceutical Sciences, 2015
Benzoxazole nucleus is one of the most important heterocyclic compounds exhibiting remarkable pharmacological activities. The present review provides a broad overview of the synthesis and pharmacological activities such as antimycobacterial, anticonvulsant, anti-inflammatory, anticancer, DNA topoisomerase inhibitor, cholesterol ester transfer protein inhibitor and miscellaneous activities.
Molbank
We have previously published on a new triazolic phosphonic α-amino ester in position 4 on the triazole ring of a naphthalene ester. The aim of the present paper was to describe its crystallographic study by XRD. The crystal structure of naphthalen-2-yl 1-(benzamido(diethoxyphosphoryl)methyl)-1H-1,2,3-triazole-4-carboxylate was determined by single-crystal X-ray diffraction. This compound crystallizes in the monoclinic system, space group P21/c. The naphthalene system is almost planar and makes dihedral angles of 67.1(2)° and 63.9(2)° with the triazole ring and the phenyl cycle, respectively. The phosphorus atom is surrounded by three oxygen atoms and one carbon atom building a distorted tetrahedron. It is also noted, that one of the two ethyl groups is disordered. In the crystal, the molecules are connected through C-H…O and N-H…O hydrogen bonds to build dimers that are linked together by C-H…O hydrogen bonds, in addition to C-H…π interactions. The presence of an intramolecular hydr...
Journal of Computational Chemistry, 1993
A cbnformational study of the 2,3,6,7-tetrahydroazepine (THA) and closely related systems has been carried out using MM3 and CHARMm molecular mechanics, AM1 semiempirical, as well as Hartree-Fock and local density functional (LDF) ab initio methods. For THA, all methods give similar optimal geometries; however, only MM3 agrees with the Hartree-Fock calculations using a 6-31G* basis set and LDF in the rank order of energies and nature of the stationary points characterized. AM1 shows serious disagreements with those results. Tetrahydrobenzazepines and a D1 receptor agonist containing the THA nucleus were studied using CHARMm, MM3, and AM1 calculations. All methods provide similar descriptions of the geometries of the conformations accessible to these compounds. However, the same disparities in the rank order of energies are observed.
Crystal structure of methyl 1,3-benzoxazole-2-carboxylate
Acta Crystallographica Section E Crystallographic Communications, 2021
The title compound, C9H7NO3, crystallizes in the monoclinic (P21) space group. In the crystal, the almost planar molecules display a flattened herringbone arrangement. Stacking molecules are slipped in the lengthwise and widthwise directions and are linked by π–π interactions [d(Cg...Cg = 3.6640 (11) Å]. The structure is characterized by strong C—H...N and weak C—H...O hydrogen bonds, and further stabilized by C–O...π interactions.
Journal of the Brazilian …, 2001
Com o objetivo de elucidar e quantificar os efeitos do solvente sobre os deslocamentos químicos de 17 O de três 5-triclorometilisoxazóis [(1a) não-, (1b) 3-metil-e (1c) 4-metil-substituído] foi realizada uma análise de regressão multilinear, utilizando os parâmetros solvatocrômicos de Kamlet-Abboud-Taft (KAT). Os deslocamentos químicos do átomo de oxigênio do anel, O1, dos compostos 1a-c mostraram dependências (em ppm) em função da polaridade-polarizabilidade do solvente de-4.8π*,-3.2π*,-8.9π*, em função da acidez do solvente (HBD) de 0.9α,-0.2α,-2.7α e em função da basicidade do solvente (HBA) de-0.4β, 1.9β, 0.9β, respectivamente. Os dados de carga líquida de O1 e de momento de dipolo, obtidos por cálculos de orbitais moleculares (AM1), são comparados com os parâmetros de efeitos do solvente determinados para os compostos 1a-c. A multilinear-regression analysis using the Kamlet-Abboud-Taft (KAT) solvatochromic parameters in order to elucidate and quantify the solvent effects on the 17 O chemical shifts of three 5-trichloromethylisoxazoles [(1a) non-, (1b) 3-methyl-and (1c) 4-methyl-substituted] is reported. The chemical shifts of ring oxygen atom, O1, of compounds 1a-c show dependencies (in ppm) on the solvent polarity-polarizability of-4.8π*,-3.2π*,-8.9π*, on the solvent hydrogenbond-donor (HBD) acidities 0.9α,-0.2α,-2.7α and the solvent hydrogen-bond-acceptor (HBA) basicities-0.4β, 1.9β, 0.9β, respectively. The data of net charges of O1 and dipole moment, obtained from MO calculations (AM1), are compared with the solvent effect parameters obtained for compounds 1a-c.
Synthesis, molecular docking and antimicrobial evaluation of novel benzoxazole derivatives
Medicinal Chemistry Research, 2016
In this research, previously and newly synthesized 5-amino-2-(4-substitutedphenyl/benzyl)benzoxazoles (3a-3l) and 2-substituted-5-(4-nitro/aminophenylsulfonamido)benzoxazoles (5a-5l, 6a-6l) were evaluated for their antimicrobial activities against Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212 and Mycobacterium tuberculosis H37RV ATCC 27294 and their drug-resistant isolates Candida albicans ATCC 10231 and Candida krusei ATCC 6258. The chemical structures of the newly synthesized compounds were characterized by IR, 1 H NMR, 13 C NMR, LC-MS and elemental analysis. Microbiological results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms at the minimum inhibitory concentration (MIC) values between 256 and 8 lg/mL. Compounds 3a, 3c and 3f exhibited significant antimycobacterial activity showing MIC value of 8 lg/mL against both M. tuberculosis and its drug-resistant isolate. InhA, the enoyl-acyl carrier protein reductase from M. tuberculosis, is one of the key enzymes in the FASII system involved in mycobacterial fatty acid elongation cycle, which has been validated as an effective antimicrobial target. Molecular docking into active site of InhA was performed on 3FNE.PDB file to understand ligandprotein interactions. The compounds obtained from this research can be used as scaffolds in the design of new potent drugs.