Bridgehead Nitrogen Atoms Research Articles

Antioxidant Activity of New Tetrazole, Thiazolidin-4-one, and Aza-beta Lactam Linking to Secondary Imines of Imidazopyridine

In this contribution, new derivatives of bicyclic fused rings with a bridgehead nitrogen atom were synthesized from the imidazo[1,2-a]pyridine derivatives C1 by reacting two moles of 2-aminopyridine and 4-aminoacetophenone with iodine in a one-pot reaction. This compound (C1) was then condensed with 2-nitrobenzaldehyde and 2,4-dichlorobenzaldehyde to form new derivatives of Schiff bases (C2 and C3). These Schiff bases were then cyclized to synthesize thiazolidin-4-one derivatives (C4 and C5), tetrazole derivatives (C6 and C7), and aza-β-lactam derivatives (C8 and C9) through the reactions with thioglycolic acid, sodium azide, and 1-naphthylisocyanate, respectively. FT-IR, 1H NMR, and 13C NMR spectroscopy were used to characterize these new compounds. In the second part of this work, the antioxidants of these compounds were measured, and results ranged from good to medium.

Mixed Thioether/Amine‐Functionalized Expanded Calixarenes, Related Macropolycycles, and Metal Complexes thereof

AbstractA series of tetraaza‐expanded calix[4]arene analogues (2–4), in which two of the four aryl groups are ethylene‐protected thiophenol components were prepared from tetraaldehyde 1. Two of these strapped macrocycles were characterized crystallographically, as well as the dipalladium complex of 4. The same tetraaldehyde had been previously used for the synthesis of a macrotricycle (5) and a macropentacycle (6), the coordination properties of which have been investigated. In particular, ligand 6 was shown to be able to encapsulate a Cu+ or a Ag+ ion in the tetrahedral coordination pocket offered by a bridgehead nitrogen atom and the three proximal thioether sulfur atoms.

Catalytic Photoredox C-H Arylation of 4-Oxo-4H-pyrido[1,2-a]pyrimidine-3-diazonium Tetrafluoroborates and Related Heteroaryl Diazonium Salts.

Irradiation of mixtures of title diazonium salts and heteroarenes with green light (510 nm) in the presence of eosin Y disodium salt (EY-Na2) as a photocatalyst furnished the corresponding arylation products in 8-63% yields. The proposed photocatalytic cycle is analogous to that proposed previously for closely related photoredox C-H arylations with aryl diazonium salts as aryl radical sources. This method has a broad substrate scope and represents a metal-free alternative for the synthesis of 3-heteroaryl-substituted 4H-quinolizin-4-ones and azino- and azolo-fused pyrimidones with a bridgehead nitrogen atom.

طريقة جديدة في تحضير مشتقات 3- ثنائي امين من الاميدازوبنزوثايازول مع دراسة فعاليتها الحيوية

In this research, new derivatives of bicyclic fused rings containing bridgehead nitrogen atom imidazo/benzothiazole were prepared from 2-aminobenzothiazole with 2-bromo-1-(4-bromophenyl)ethan-1-one to form compound A1. Then, through the Mannich reaction, compound A2 was prepared from compound A1 with formaldehyde and 4-aminoacetophenone. Schiff bases A3-A6 were prepared from condensation reaction between compound A2 with different amines. Finally, the reduction reaction was accomplished by using NaBH4 to reduce the imine group to forming new compounds A7-A10. These compounds were characterized by FTIR, 1HNMR, and 13CNMR. The prepared compounds showed biological activity against some microorganisms.

Biological Activity of Condensed Pyridine Derivatives with a Bridgehead Nitrogen Atom

Biological Activity of Condensed Pyridine Derivatives with a Bridgehead Nitrogen Atom

Heterocyclic system containing bridgehead nitrogen atom: Substituted 1,2,3-Triazolo [3,4-b]-1,3,4-Thiadiazole derivative useful for the treatment of breast cancer and other diseases

There has been considerable interest in the development of novel compounds with anticonvulsant, analgesic, anti-inflammatory, antimicrobial, antimycobecterial, antitumour, and antitubercular activities. 1,3,4-thiadiazole constitute an important class of compound for new drug development. They have interesting pharmacophore that display a broad spectrum of Pharmacological activity. The 1,3,4-thiadiazole compound is an interesting heterocycling group that has been used to synthesize a variety of useful bioactive compounds. The stability of thiadiazole nucleus has inspired medicinal chemist to carry out various structural variation in the ring. The marketed drugs such as acetazolamide and methazolamide etc showed their therapeutic potential Therefore; many researchers have synthesized these compounds as target structures and evaluated their biological activities. This review highlights the various Pharmacological activities associated with 1,3,4-thiadiazole ring system.

Biological Applications of Imidazothiazole Scaffolds: A Current Review

Due to the broad-spectrum biological activities, fused heterocyclic compounds are one of the most important systems in medicinal chemistry. Among them, the imidazothiazole which contains a bridgehead nitrogen atom has a vital role because of various applications such as anticancer, antimalarial, antiviral, etc. Designing various imidazothiazole scaffolds has become more important because of their several biological applications. The present review paper discusses the numerous biological applications of imidazothiazole scaffolds in the field of medicine. The review would be useful in future drug design for the development of more promising drug-like scaffolds.

Visible-Light-Prompted Synthesis and Binding Studies of 5,6-Dihydroimidazo[2,1-b]thiazoles with BSA and DNA Using Biophysical and Computational Methods.

Fused heterocyclic systems containing a bridgehead nitrogen atom have emerged as imperative pharmacophores in the design and development of new drugs. Among these heterocyclic moieties, the imidazothiazole scaffold has long been used in medicinal chemistry for the treatment of various diseases. In this study, we have established a simplistic and environmentally safe regioselective protocol for the synthesis of 5,6-dihydroimidazo[2,1-b]thiazole derivatives from easily available reactants. The reaction proceeds through in situ formation of the α-bromodiketones ensuing trap with imidazolidine-2-thione to provide these versatile bicyclic heterocycles in excellent yields. The synthesized compounds were screened through the molecular docking approach for the most stable complex formation with bovine serum albumin (BSA) and calf thymus deoxyribonucleic acid (ctDNA). The selected compound was further studied using ex vivo binding studies, which revealed moderate interactions with BSA and ctDNA. The binding studies were performed using biophysical approaches including UV-visible spectroscopy, steady-state fluorescence, circular dichroism (CD), and viscosity parameters.

Condensed Pyridopyrimidines and Pyridopyrazines Containing a Bridgehead Nitrogen Atom: Synthesis, Chemical Properties and Biological Activity

The investigation of effective and green synthetic routes to approach to novel fused heterocycles with pyridopyrimidine and pyridopyrazine scaffolds stirs up broad interest from scientists as they are capable of providing valuable properties such as anticancer and antimicrobial activities and they are proved γ-secretase modulators, polymers, and corrosion inhibitors. This causes a steady increase in the number of publications on titled condensed systems. The present review article summarizes recent literature data from 2010 to 2020 on the methods of synthesis, chemical transformations and biological properties of condensed bicyclic systems of pyridopyrimidine and pyridopyrazine with a bridgehead nitrogen atom to establish the current state of the art in this area.

Heterocyclic Bridgehead Nitrogen Atom System: Review on [1,2,4] Triazolo[3,4-b] [1,3,4] thiadiazole and Its Pharmacological Screening.

There has been considerable interest in the development of novel anticonvulsant compounds, , analgesic, anti-inflammatory, antimicrobial, antimycobacterial, antitumour, and antitubercular activities. 1,3,4-thiadiazole constitute Significant class of compounds for new drugs development. They Have an interesting pharmacophore displaying a wide range of pharmacological activity. The 1,3,4-thiadiazole compound is an interesting heterocycle. A group that was used to synthesise a variety of useful bioactive compounds. The stability of the thiadiazole nucleus has inspired the medicinal chemist to perform various structural variations in the ring. Marketed drugs such as acetazolamide and methazolamide have shown their therapeutic potential Therefore, many researchers have identified these compounds as target structures and evaluated their biological activities. This review highlights the different pharmacological activities associated with the 1,3,4-thiadiazole ring system.

Condensation of 2-Amino-1,3-thiazole Salts and Benzo Analogs with Trifluoroacetylacetone

The condensation of 2-amino-1,3-thiazolium perchlorates and their benzo analogs with trifluoro­acetyl­acetone in acetic acid afforded the corresponding [1,3]thiazolo[3,2-a]pyrimidinium, pyrimido[2,1-b][1,3]benzothiazolium, and naphtho[2′,1′:4,5][1,3]thiazolo[3,2-a]pyrimidinium salts as a single isomer in which the trifluoromethyl group is located in the γ-position with respect to the bridgehead nitrogen atom. The structure of the synthesized compounds was confirmed by 1H NMR spectra and elemental analyses.

Synthesis of Quinone Derivatives of Benzannelated Heterocycles with Bridgehead Nitrogen

A facile synthesis of para-quinones derived from fused benzimidazoles with a bridgehead nitrogen atom was developed. The heterocyclic quinone core formed as a result of reductive cyclization of ortho-nitroarenes containing alicyclic and aromatic azaheterocycles. Functionalization of 1,2,3,4-tetrahydro- and pyrido[1,2-a]benzimidazoles via SEAr, condensation, and reduction reactions allowed synthesis of amino derivatives which were oxidized with KNO3 in H2SO4 to obtain novel heterocyclic quinones.

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli-Cushman protocol.

The Castagnoli–Cushman reaction of 3,4-dihydroisoquinolines with glutaric anhydride, its oxygen and sulfur analogues was investigated as a one-step approach to the benzo[a]quinolizidine system and its heterocyclic analogs. An extension towards the pyrrolo[2,1-a]isoquinoline system was achieved with the use of succinic anhydride. The results are evidence of an unexplored method for the access of the aforementioned tricyclic annelated systems incorporating a bridgehead nitrogen atom. The structures and relative configurations of the new compounds were established by means of 1D and 2D NMR techniques. The reactions between 1-methyldihydroisoquinoline and glutaric, diglycolic and succinic anhydrides yielded unexpected isoquinoline derivatives containing an exocyclic double bond. The compounds prepared bear the potential to become building blocks for future synthetic bioactive molecules.

Synthesis of Functionalized Bridged Bicyclic Sulfonamides with a Bridgehead Nitrogen Atom

Two approaches to the synthesis of functionalized bridged bicyclic sulfonamides with a bridgehead nitrogen atom were developed. The target compounds were obtained either by introduction of a CH2SO2 bridge into functionalized monocyclic substrates or by final‐step carboxylation of parent bicyclic cores. The described methods allowed preparation of the final products on a multigram scale.

Selenoamides as powerful scaffold to build imidazo[1,5-a]pyridines using a grinding protocol

We describe the synthetic application of a family of selenoamides [R–C(Se)NHCH2R’ (R = Fc, Aryl, Het, alkyl) tethered to N-heterocyclic motifs (R’ = 2-pyridyl and 2-thiazolyl) obtained from their corresponding Fischer ethoxy carbene complexes [R–C(Cr(CO)5)OEt] using a tandem procedure that involves an aminolysis/seleniurative demetallation. The selenoamides obtained are used as accessible building-block to easily obtain a two-ring fused system with a bridge-head nitrogen atom. This study reveals that CSe bond can be readily and speedily activated with iodine at room temperature, in grinding conditions, for obtaining a family of imidazo[1,5-a]pyridines in good to excellent yields in only 1 min of reaction time. This methodology was successfully extended to the synthesis of ferrocenyl imidazo[1,5-b]thiazole in excellent yield.

Twisting and Turning the Sulfonamide Bond: A Synthetic, Quantum Chemical, and Crystallographic Study.

Structural restriction of the sulfonamide bond was used to design sultams with abnormal geometric parameters. Based on analysis of tertiary aliphatic sulfonamides published in the Cambridge crystallographic database, Paquette's sultams (i.e., bridged bicyclic sultams with a bridgehead nitrogen atom) were outlined, and a number of these compounds (including the novel smallest representative, 2-thia-1-azabicyclo[2.1.1]hexane 2,2-dioxide) were synthesized by cyclization of the corresponding amino sulfonyl fluorides. A series of tertiary aliphatic sulfonamides was studied by crystallographic and quantum chemical methods. It was found that the s-character of the nitrogen lone pair is the most important factor defining properties of the S-N bond. Thus, going from the sp3-hybrid lone pair in common sulfonamides to the sp-like lone pair in the smallest Paquette's sultam resulted in an increase in S-N bond length by ca. 0.06 Å. The strain energy of ca. 30 kcal/mol was predicted for the latter compound, which was higher than for any existing sulfonamides studied.

The Role of Hyperconjugation on the Structure and C–H Stretching Frequencies of 3,3′-Ethane-1,2-diyl- bis-1,3,5-triazabicyclo[3.2.1]octane (ETABOC): An X-Ray Structure and Vibrational Study

Structural and vibrational studies have been carried out for the most stable conformer of 3,3′-ethane-1,2-diyl-bis-1,3,5-triazabicyclo[3.2.1]octane (ETABOC) at the DFT/B3LYP/6-31G(dp) level using the Gaussian 03 software. In light of the computed vibrational parameters, the observed IR Bolhmann bands for the C2V, C2, and Ci symmetrical structures of ETABOC have been analyzed. Hyperconjugative interaction was done by Natural Bond Orbital Analysis. Interpretation of hyperconjugative interaction involving the lone pairs on the bridgehead nitrogen atoms with the neighboring C–N and C–C bonds defines the conformational preference of the title compound. The recorded X-ray diffraction bond parameters were compared with theoretical values calculated at B3LYP/6-31G(d,p) and HF/6-31G(d,p) level of theory showed that ETABOC adopts a chair conformation and possesses an inversion center.

Synergy between Experimental and Theoretical Results of Some Reactions of Annelated 1,3-Azaphospholes.

Computational calculations have been used successfully to explain the reactivity of the >C=P- functionality in pyrido-annelated 1,3-azaphospholes. Theoretical investigation at the Density Functional Theory (DFT) level shows that the lone pair of the bridgehead nitrogen atoms is involved in extended conjugation, due to which electron density increases considerably in the five-membered azaphosphole ring. The electron density in the azaphosphole is further enhanced by the presence of an ester group at the 3-position making the >C=P- functionality electron-rich. Thus, 1,3-azaphospholo[5,1-a]pyridine, i.e., 2-phosphaindolizine having ester group at the 3-position only does not undergo Diels-Alder (DA) reaction with an electron rich diene, such as 2,3-dimethyl-1,3-butadiene (DMB). However, an ester group at 1-position acts as electron-sink, due to which transfer of the electron density to the >C=P- moiety is checked and DA reaction occurs across the >C=P- functionality. The coordination of the Lewis acid to the carbonyl group at the 3-position raises the activation barrier, while it is lowered remarkably when it is coordinated to the P atom. Furthermore, the attack of 1,3-butadiene on the Si face of the P-coordinated (o-menthoxy)aluminum dichloride complex is a lower activation energy path. Fukui functions could be used to explain relative reactivities of indolizine and 2-phosphaindolizine towards electrophilic substitution reactions.

Convenient Way to the Synthesis of Polycyclic Fused Benzimidazole Derivatives with a Bridgehead Nitrogen Atom

Effective synthesis was developed for 1,2,3,4-tetrahydropyrido- and pyrido[1,2-a]benzimidazole-7,8-diamines that underlie the preparation of new polyazaheterocycles: pyrido[1,2-а]imidazo[4,5-f]-benzimidazole, 7Н-pyrido[1,2-а]imidazo[4,5-f]benzotriazole, pyrido[1,2-а]imidazo[4,5-g]quinoxaline.

Investigation on the Effects of Antimicrobial imidazo[2,1-b]thiazole Derivatives on the Genitourinary Microflora.

Fused five-membered heterocyclic rings containing bridgehead nitrogen atom are particularly versatile in the field of medicinal chemistry because of their different biological activities. Among them, the imidazo[2,1-b]thiazole is an attractive fused heterocyclic core that has been extensively studied. The aim of the current study was to study the therapeutic applications of imidazo[2,1- b]thiazole derivatives as antimicrobial agents for the treatment of genitourinary infections. A traditional synthetic methodology was involved to obtain a small series of imidazothiazole derivatives. Herein, we report the antimicrobial activity of the imidazo[2,1-b]thiazole or imidazo[2,1- b]thiazolidine derivatives against selected fungi, Gram-positive and Gram-negative bacteria. Moreover, experiments were carried out to investigate the interference towards the endogenous microbiota. The most interesting of the series are the thiocyano derivatives (19, 23) showing a good profile for the treatment of genitourinary infections: a spectrum of activity covering both bacteria and fungi together with a reduced impact versus critical lines of Lactobacillus exerting defense against pathogens.