scholarly journals Synthesis, Characterization, and Antibacterial and Anti-Inflammatory Activities of New Pyrimidine and Thiophene Derivatives

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Siham Lahsasni ◽  
Dunya A. M. Al-Hemyari ◽  
Hazem A. Ghabbour ◽  
Yahia Nasser Mabkhoot ◽  
Fadilah S. Aleanizy ◽  
...  
Keyword(s):  
Nucleophilic Substitution ◽  
Phenyl Isothiocyanate ◽  
Standard Drug ◽  
Thiourea Derivatives ◽  
X Ray ◽  
X Ray Crystallography ◽  
Lead Compounds ◽  
Antimicrobial Studies ◽  
Thiophene Derivatives ◽  
Anti Inflammatory

Substituted[4,5]thieno[2,3-d]thiazolo[3,2-a]pyrimidin-5-one (3a–b) and pyrimidin-5(6H)-imine (3c–e) were synthesized via reaction of the starting compounds, ethyl 2-amino-substituted[b]thiophene-3-carboxylate (2a–c) and 2-amino-substituted [b]thiophene-3-carbonitrile (2d–f), respectively, with 2-bromothiazole. Synthesis of (bromo-substituted[b]thiophen-2-yl)alkanamide derivatives (4a–e) and thieno[2,3-d][1,3]oxazin-4-imine derivative (5) was accomplished via reaction of the starting compounds with bromoalkyl chloride through nucleophilic substitution; however, for the synthesis of compound 5, nucleophilic substitution was followed by nucleophilic addition to a nitrile group to form the oxazinimine ring. 1-(3-cyano-substituted[b]thiophen-2-yl)-3-(4-(trifluoromethyl)phenyl)thiourea derivatives (6a–c) were obtained via reaction of the starting compounds (2d–f) and 4-(trifluoromethyl phenyl)isothiocyanate. The lead compounds (2d–f) rapidly reacted with 4-(trifluoromethyl)benzaldehyde or 4-(2-pyridyl)benzaldehyde in acidic medium to yield compounds (7a–f) in large quantities. X-ray crystallography of compounds 4c and 7e confirmed their structures. Antimicrobial studies revealed that compound 6a was equally potent to ampicillin against Bacillus strains. Moreover, compounds 3e, 4d, and 6a possessed greater anti-inflammatory potency than that of the standard drug.

scholarly journals Neue Synthesewege zu neutralen gemischtsubstituierten Eisen-Schwefel-Clustern / Novel Synthetic Pathways to Neutral Mixed-Ligand Iron-Sulfur Clusters

1996 ◽  
Vol 51 (7) ◽  
pp. 1040-1048 ◽  
Author(s):  
M. Harmjanz ◽  
C. Junghans ◽  
U.-A. Opitz ◽  
B. Bahlmann ◽  
S. Pohl
Keyword(s):  
Elemental Sulfur ◽  
Large Excess ◽  
Iron Sulfur Clusters ◽  
Thiourea Derivatives ◽  
X Ray ◽  
X Ray Crystallography ◽  
Iron Sulfur ◽  
Neutral Ligands ◽  
High Yields ◽  
Sulfur Donor

The reaction of [Fe(NiSiMe3)2)2] with thiols RSH, elemental sulfur, and neutral ligands L (with sulfur donor atoms, e. g. thiourea derivatives) gives [Fe4S4(SR)2L2] clusters in high yields. The structure of [Fe4S4(2.4.6-(C3H7)3C6H2-S)2(dpdmi)2] (dpdmi: diisopropyldimethyl- imidazolthion) was determined by X-ray crystallography.When [Fe4S4I4]2- is reacted with a large excess of PMePh2 or PMe2Ph [F6S6I2(PMePh2)4] and [Fe6S6l2(PMe2Ph)4]. respectively, are obtained in nearly quantitative yield. Basket-like structures of the [Fe6S6]2+ cores were detected by X-ray structure analysis. While [Fe4S4(SR)4]2- clusters do not react with phosphanes at ambient temperature 2:2 functional­ized species like [Fe4S4(SR)2(tmtu)2] lead to basket-type clusters [Fe6S6(SR)2(PR3)4].

scholarly journals Parallel Screening of Low Molecular Weight Fragment Libraries

2012 ◽  
Vol 18 (2) ◽  
pp. 147-159 ◽  
Author(s):  
Jerome Wielens ◽  
Stephen J. Headey ◽  
David I. Rhodes ◽  
Roger J. Mulder ◽  
Olan Dolezal ◽  
...  
Keyword(s):  
Screening Methods ◽  
Resonance Spectroscopy ◽  
Lead Discovery ◽  
X Ray ◽  
X Ray Crystallography ◽  
Fragment Screening ◽  
Lead Compounds ◽  
Preliminary Identification ◽  
Std Nmr ◽  
Fragment Libraries

Fragment screening is becoming widely accepted as a technique to identify hit compounds for the development of novel lead compounds. In neighboring laboratories, we have recently, and independently, performed a fragment screening campaign on the HIV-1 integrase core domain (IN) using similar commercially purchased fragment libraries. The two campaigns used different screening methods for the preliminary identification of fragment hits; one used saturation transfer difference nuclear magnetic resonance spectroscopy (STD-NMR), and the other used surface plasmon resonance (SPR) spectroscopy. Both initial screens were followed by X-ray crystallography. Using the STD-NMR/X-ray approach, 15 IN/fragment complexes were identified, whereas the SPR/X-ray approach found 6 complexes. In this article, we compare the approaches that were taken by each group and the results obtained, and we look at what factors could potentially influence the final results. We find that despite using different approaches with little overlap of initial hits, both approaches identified binding sites on IN that provided a basis for fragment-based lead discovery and further lead development. Comparison of hits identified in the two studies highlights a key role for both the conditions under which fragment binding is measured and the criteria selected to classify hits.

Synthesis, Characterization and Crystal Structures of 1,2-Disubstituted Ferrocenyl Stibines

2012 ◽  
Vol 67 (1) ◽  
pp. 36-40
Author(s):  
Diego Pérez ◽  
Pankaj Sharma ◽  
Ana M. Ortiz ◽  
Armando Cabrera ◽  
Simon Hernández ◽  
...  
Keyword(s):  
Solid State ◽  
Acetic Anhydride ◽  
Nucleophilic Substitution ◽  
Sodium Hydroxide ◽  
Crystal Structures ◽  
Analytical Methods ◽  
Molecular Structures ◽  
X Ray ◽  
X Ray Crystallography ◽  
Pendant Arm

New 1,2-disubstituted ferrocenyl stibines containing a -CH2OR pendant arm were synthesized and characterized by various spectral and analytical methods. Nucleophilic substitution of rac-diphenyl[( 2-trimethylammoniomethylferrocen-1-yl)]stibine iodide by methanol produces compound Fc(CH2OMe)SbPh2 (1). The acetylation of diphenyl(2-dimethylaminomethylferrocen-1-yl)stibine by acetic anhydride affords compound Fc(CH2OCOCH3)SbPh2 (2), which on further reaction with sodium hydroxide affords the alcohol Fc(CH2OH)SbPh2 (3). The molecular structures of the stibines 1, 2 and 3 were determined by X-ray crystallography. None of the heterobimetallic compounds containing a -CH2OR arm shows hypervalent interactions in the solid state. By contrast, hypervalent interactions were found in ferrocenyl stibines with a -CH2NR2 pendant arm.

Modelling SN2 nucleophilic substitution at silicon by structural correlation with X-ray crystallography and NMR spectroscopy

2003 ◽  
Vol 667 (1-2) ◽  
pp. 66-72 ◽  
Author(s):  
Alan R Bassindale ◽  
David J Parker ◽  
Peter G Taylor ◽  
Norbert Auner ◽  
Bernhard Herrschaft
Keyword(s):  
Nmr Spectroscopy ◽  
Nucleophilic Substitution ◽  
X Ray ◽  
X Ray Crystallography ◽  
Structural Correlation

scholarly journals An Automated Microscale Thermophoresis Screening Approach for Fragment-Based Lead Discovery

2015 ◽  
Vol 21 (4) ◽  
pp. 414-421 ◽  
Author(s):  
Pawel Linke ◽  
Kwame Amaning ◽  
Melanie Maschberger ◽  
Francois Vallee ◽  
Valerie Steier ◽  
...  
Keyword(s):  
Protein Denaturation ◽  
Lead Discovery ◽  
X Ray ◽  
X Ray Crystallography ◽  
Fragment Screening ◽  
Lead Compounds ◽  
Microscale Thermophoresis ◽  
Biophysical Techniques ◽  
Orthogonal Methods ◽  
Induced Aggregation

Fragment-based lead discovery has proved to be an effective alternative to high-throughput screenings in identifying chemical matter that can be developed into robust lead compounds. The search for optimal combinations of biophysical techniques that can correctly and efficiently identify and quantify binding can be challenging due to the physicochemical properties of fragments. In order to minimize the time and costs of screening, optimal combinations of biophysical techniques with maximal information content, sensitivity, and robustness are needed. Here we describe an approach utilizing automated microscale thermophoresis (MST) affinity screening to identify fragments active against MEK1 kinase. MST identified multiple hits that were confirmed by X-ray crystallography but not detected by orthogonal methods. Furthermore, MST also provided information about ligand-induced aggregation and protein denaturation. The technique delivered a large number of binders while reducing experimentation time and sample consumption, demonstrating the potential of MST to execute and maximize the efficacy of fragment screening campaigns.

A Concise Synthesis of 24,25-Dihydro-6-epi-Monanchosterol A

Synlett ◽  
2021 ◽  
Author(s):  
Hans-Günther Schmalz ◽  
Ömer Taspinar ◽  
Vladimir Kjartan Stojadinovic ◽  
Jörg-Martin Neudörfl
Keyword(s):  
Double Bond ◽  
Title Compound ◽  
Protecting Group ◽  
Structural Analogue ◽  
X Ray ◽  
X Ray Crystallography ◽  
Anti Inflammatory ◽  
Aldol Addition ◽  
Optimized Conditions

AbstractWe report the first synthetic entry to a steroid with an unusual bicyclo[4.3.1]dec-3-en-10-one A/B ring substructure as a close structural analogue of the anti-inflammatory monanchosterols. Under optimized conditions, regioselective cis-dihydroxylation of the Δ5-double bond of 7-dehydrocholesterol and subsequent Criegee oxidation yields the corresponding 5,6-seco-steroid as a pure Z-isomer which upon treatment with K2CO3 in MeOH diastereoselectively affords 24,25-dihydro-6-epi-monanchosterol A through intramolecular aldol addition (cyclization). The developed three-step sequence proceeds in 17% overall yield without the need of any protecting group. The title compound was characterized by X-ray crystallography.

scholarly journals Synthesis, antibacterial activity and docking studies of chloroacetamide derivatives

2019 ◽  
Vol 10 (4) ◽  
pp. 358-366 ◽  
Author(s):  
Shahzad Murtaza ◽  
Ataf Ali Altaf ◽  
Muhammad Hamayun ◽  
Kiran Iftikhar ◽  
Muhammad Nawaz Tahir ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Topoisomerase Ii ◽  
Docking Studies ◽  
Diffusion Method ◽  
Replication Process ◽  
Standard Drug ◽  
X Ray Crystallography ◽  
Lead Compounds ◽  
Drug Molecules ◽  
Comparable Activity

Structural modification of lead compounds is a great challenge in organic synthesis. Introduction of different functional groups not only modify the structure of starting material but also improve their biological activeness. Small synthetic molecules are favored in spite of the reality that majority of drug molecules derived from natural sources, are in vogue. In the present work, acetamide derivatives were synthesized using chloroacetyl chloride. After synthesizing targeted series of acetamide derivatives these compounds were further modified using different amines including 2-aminobenzene thiol, benzyl amine, benzene 1,4-diamine, 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one, 4-aminophenol, hydrazine and 4-amino-N-(5-methylisoxazol-3-yl)benzenesulfonamide. All of these synthesized compounds were characterized by FT-IR, 1H NMR, 13C NMR and X-ray crystallography. The compounds were assessed for their anti-bacterial activity using disc diffusion method against Staphylococcus aureus and Escherichia coli. The compounds were found to exhibit comparable activity to the standard drug used. This was further supported by molecular docking studies using bacterial DNA gyrase and Topoisomerase II targets causing bacterial death as they are major bacterial proteins known to be involved in transcription and replication process. Results proved that the compound 2b was the most efficacious antimicrobial compound among the synthesized set of compounds. To tackle the growing drug resistance acetamide based functionalities can be regarded as the active lead compounds to target different drug resistance microorganism.

scholarly journals Verruculosins A–B, New Oligophenalenone Dimers from the Soft Coral-Derived Fungus Talaromyces verruculosus

Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 516 ◽  
Author(s):  
Minghui Wang ◽  
Longhe Yang ◽  
Liubin Feng ◽  
Fan Hu ◽  
Fang Zhang ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Spectroscopic Data ◽  
Soft Coral ◽  
Optical Rotation ◽  
Tyrosine Phosphatase ◽  
X Ray ◽  
X Ray Crystallography ◽  
Lead Compounds ◽  
Ic50 Values ◽  
New Compounds

In an effort to discover new bioactive anti-tumor lead compounds, a specific tyrosine phosphatase CDC25B and an Erb family receptor EGFR were selected as drug screening targets. This work led to the investigation of the soft coral-derived fungus Talaromyces verruculosus and identification of two new oligophenalenone dimers, verruculosins A–B (1–2), along with three known analogues, bacillisporin F (3), duclauxin (4), and xenoclauxin (5). Compound 1 was the first structure of the oligophenalenone dimer possessing a unique octacyclic skeleton. The detailed structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic data, X-ray crystallography, optical rotation, Electronic Circular Dichroism (ECD) analysis, and nuclear magnetic resonance (NMR) calculations. Among which, compounds 1, 3, and 5 exhibited modest inhibitory activity against CDC25B with IC50 values of 0.38 ± 0.03, 0.40 ± 0.02, and 0.26 ± 0.06 µM, respectively.

Sign in / Sign up

Export Citation Format

Share Document