Pentacyclic Triterpenoids with Nitrogen-Containing Heterocyclic Moiety,Privileged Hybrids in Anticancer Drug Discovery

Pentacyclic triterpenoids are well-known phytochemicals with various biological activities commonly found in plants as secondary metabolites. The wide range of biological activities exhibited by triterpenoids has made them the most valuable sources of pharmacological agents. A number of novel triterpenoid derivatives with many skeletal modifications have been developed. The most important modifications are the formation of analogues or derivatives with nitrogen-containing heterocyclic scaffolds. The derivatives with nitrogen-containing heterocyclic compounds are among the most promising candidate for the development of novel therapeutic drugs. About 75% of FDA-approved drugs are nitrogen-containing heterocyclic moieties. The unique properties of heterocyclic compounds have encouraged many researchers to develop new triterpenoid analogous with pharmacological activities. In this review, we discuss recent advances of nitrogen-containing heterocyclic triterpenoids as potential therapeutic agents. This comprehensive review will assist medicinal chemists to understand new strategies that can result in the development of compounds with potential therapeutic efficacy.     

Allobetulin and its derivatives: synthesis and biological activity

This review covers the chemistry of allobetulin analogs, including their formation by rearrangement from betulin derivatives, their further derivatisation, their fusion with heterocyclic rings, and any further rearrangements of allobetulin compounds including ring opening, ring contraction and ring expansion reactions. In the last part, the most important biological activities of allobetulin derivatives are listed. One hundred and fifteen references are cited and the relevant literature is covered, starting in 1922 up to the end of 2010.     

3D-QSAR study on heterocyclic topoisomerase II inhibitors using CoMSIA

Selective topoisomerase II (Topo II) inhibitors have interested to a great extent for the design of new antitumoral compounds in recent years. Comparative molecular similarity indices analysis (CoMSIA) was performed on a series of previously synthesized benzoxazole, benzimidazole, and oxazolo(4,5-b)pyridine derivatives as eukaryotic Topo II inhibitors. A training set of 16 heterocyclic compounds was used to establish the CoMSIA model. They were constructed and geometrically optimized using SYBYL v7.0. The predictive ability of the model was assessed using a test set of 7 compounds. The best model has demonstrated a good fit having r2 value of 0.968 and cross-validated coefficient q2 value as 0.562 including steric and hydrophobic fields. The hydrophobic interactions showed a dominant role for increasing Topo II inhibitor activity and hydrophilic substituent was found more important than hydrophobic one on the 5 or 6 position of benzazole moiety. The model obtained from the present study can be useful for the modification and/or evaluation of the development of new Topo II inhibitors as potential antitumor compounds.     

Cyanoamino compounds in synthesis syntheses of some heterocycles

Transformations of some heterocyclic cyanoamino compounds leading to various heterocyclic systems are described.s-Triazolo (1,5-α)azines are obtained either in a direct synthetic approach or via the substituted aminotetrazoles, substituted 3-amino-5-oxo-1,2,4-oxadiazolines, and fromN-ethoxycarbonylN′-heteroaryl thioureas orN-heteroarylN′-hydroxyguanidine. The cyanoamino group reacts also witho-difunctional benzenes to give the corresponding substituted derivatives of benzimidazole, benzoxazole or benzothiazole.     

Pyridine Scaffolds,Phenols and Derivatives of Azo Moiety: Current Therapeutic Perspectives

Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure–activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years.     

Synthesis of heterocyclic compounds from cyclohexane-1,3-diones (review)

The literature data on the synthesis of partially hydrogenated heterocyclic compounds containing a 3-oxocyclohexene structural fragment condensed with five-, six-, or seven-membered oxygen-, nitrogen-, and sulfur-containing heterorings from cyclohexane-1,3-diones and their derivatives are examined in this review.     

The Chemistry of Acetylpyrazoles and Its Utility in Heterocyclic Synthesis

A literature survey revealed that a great deal of interest has been focused on the synthesis of functionalized pyrazole derivatives due to their synthetic and biological potentialities. The pharmacological activities that have been found for some pyrazole derivatives include selective enzyme inhibition, antiviral, estrogen receptor agonist, anti‐inflammatory, anticancer, antiobesity, and antitumor properties. Other activities such as potential inhibitors of HIV‐1, pesticides, fungicides, and antihypertensive agents were reported for other pyrazole derivatives. This review summarizes the synthetic methods and reactions of 3‐acetyl‐pyrazoles, 4‐acetyl‐pyrazoles, and 3,4‐di‐acetyl‐pyrazoles. Most reaction types have been successfully applied and used in the production of biologically active compounds. The aim of this review is to focus mainly on the utility of acetylpyrazole derivatives in the synthesis of heterocyclic compounds during the period 1990–2018.     

New Fluorescent Nickel(II) Complexes as a Catalyst for Biodiesel Formation: Synthesis,Structure, Spectral Properties,and DFT Calculations

Russian Journal of Organic Chemistry - Two fluorescent heterocyclic ligands were obtained by reduction of imidazo[4,5-e][2,1]benzoxazole derivatives with Fe/HCl. New fluorescent nickel(II)...     

A new method of synthesis of some 2-aryl and 2-heterocyclic benzimidazole,benzoxazole and benzothiazole derivatives

A new one-step facile method for the synthesis of some benzimidazole, benzoxazole and benzothiazole derivatives is described. The method involves the action of aromatic and heterocyclic selenoamides on some o-phenylenediamine, o-aminophenol and o-aminothiophenol and their derivatives.     

Thio-claisen rearrangement in the synthesis of sulfur-containing heterocyclic compounds (review)

The review is devoted to literature information on the mechanism of the thio-Claisen rearrangement of allyl aryl (heteryl) sulfides and their use in the synthesis of five- and six-membered sulfur-containing heterocyclic compounds, including derivatives of dihydrobenzothiophene and thiochromane.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 435–449, April, 1980.     

Aminopyrimidine derivatives as protein kinases inhibitors. Molecular design,synthesis, and biologic activity

The review compiles the strategies and methods of development of aminopyrimidine derivatives as targeted antitumor pharmaceuticals. The advances in organic and heterocyclic chemistry are considered in the targeted synthesis of aminopyrimidine derivatives whose series contains the most demanded and efficient antitrumor pharmaceuticals. The problems of preparation of compounds with multikinase activity profile and the construction of chimeric molecules are discussed.     

Synthesis of macrocyclic bis(phenylbenzoxazole) derivatives via tandem claisen rearrangement and their fluorescence behavior

Novel macrocyclic bis(phenylbenzoxazole) derivatives were easily synthesized from macrocyclic isobutenyl bis(amide‐ether)s by tandem Claisen rearrangement and subsequent intramolecular cyclization of the amide‐phenol intermediates. The position of substitution of the oligoethylene glycol moiety on the phenylamido groups of the macrocycles did not have a large effect on the yields of the bis(benzoxazole)s for the meta and para derivatives. The fluorescence quantum yields of most of the macrocyclic bis(benzoxa‐zole)s were lower than those of the corresponding nonmacrocyclic bis(benzoxazole) model compounds. The quantum yields of the para‐substituted macrocyclic bis(benzoxazole)s were clearly lower than those of the model compounds and decreased with increasing length of the oligoethylene chain.     

Enantioselective Synthesis of Spiro Heterocyclic Compounds Using a Combination of Organocatalysis and Transition-Metal Catalysis

Over the last ten years, the combination of organocatalysis with transition metal (TM) catalysis has become one of the most important toolboxes used for synthesizing optically pure compounds containing chiral quaternary centers, including spiro heterocyclic molecules. The dominant method in the enantioselective synthesis of spiro heterocyclic compounds based on synergistic catalysis includes chiral aminocatalysis and NHC catalysis, as already established covalent organocatalytic strategies. Another area of organocatalysis widely combined with TM catalysis producing enantiomerically enriched spiro heterocyclic compounds is non-covalent catalysis, dominated by chiral phosphoric acids, thiourea, and squaramide derivatives. This review article aims to summarize enantioselective methods used for constructing spirocyclic heterocycles based on a combination of organocatalysis and transition metal catalysis.     

若干杂环模型化合物的热氧化稳定性

<正> 自五十年代以来,耐热的杂环高分子取得了很多进展。曾报道聚酰亚胺、聚苯并咪唑、聚苯并噻唑、聚苯并噁唑、聚喹噁林及聚苯并噁嗪酮等都是性能较好的耐热高分子,而有些在工业上已得到应用。我们在进行芳杂环二腈聚合的工作中,曾将上述杂环结构引入二腈,以期获得性能优良的耐热高分子,所得结果已陆续报道。     

Heterocyclization of acylthiosemicarbazides

The review summarizes published data on the behavior and reactions of acylthiosemicarbazides and their derivatives, which lead to the formation of heterocyclic systems, including methods of preparation in addition to synthesis of pyrrole, thiazole, thiadiazole, thiadiazolidine, and triazole derivatives as well as fused heterocyclic compounds. J. Heterocyclic Chem., (2012).     

Chemistry and heterocyclization of thiosemicarbazones

The review summarizes the literatures dealing with the synthesis of thiosemicarbazone derivatives, chemical reactions and their applications in the synthesis of important heterocyclic as well as fused heterocyclic compounds J. Heterocyclic Chem., (2012).     

New benzoxazole-based sulphonamide hybrids analogs as potent inhibitors of α-amylase and α-glucosidase: Synthesis and in vitro evaluation along with in silico study

The development of drugs resistance in diabetes mellitus is a growing clinical problem, creates many challenges for patient. To overcome these problems, there is a serious deficiency of anti-diabetic agents, may be synthesized that inhibit alpha amylase and alpha glucosidase activity. Here, we have design and synthesized benzoxazole based sulphonamide derivatives and evaluated for their anti-diabetic activity. Twenty-two benzoxazole based sulphonamide derivatives were synthesized by reacting 2-aminophenol with carbon disulphide in the presence of base (Et3N) to obtained 2-marcapto benzoxazole which was further dissolved in ethanol by slow addition of different substituted phenacyl bromide in the presence of triethylamine, afforded varied S-substituted benzoxazole products. These products were dissolved in ethanol and hydrazine hydrate was added an excess in the presence of acetic acid to gives Schiff base. This Schiff base products were further dissolved in THF along with different substituted benzene sulphonyl chloride followed by addition of few drops of Et3N, yielded benzoxazole based sulphonamide derivatives (1–22). Moreover, SAR was established for the synthesized compounds and molecular docking studies were conducted for the potent moieties in order to explore the binding modalities of analogs. Among the tested series few analogues were found few folds better potential than standard drug but analog 1 (IC₅₀ = 1.10 ± 0.20 µM, 1.20 ± 0.30 µM), showed promising anti-diabetic activity against α-amylase and α-glucosidase (11.12 ± 0.15 µM and 11.29 ± 0.07 µM respectively).     

Inhibiting effects of benzamide derivatives on the corrosion of mild steel in hydrochloric acid solution

The inhibition effect of new heterocyclic compounds, namely N-(cyanomethyl)benzamide (BENZA) and N-[(1H-tetrazol-5-yl)methyl]benzamide (BENZA-TET), on mild steel corrosion 1 M HCl was investigated using electrochemical measurements. The results indicated that the inhibition efficiency depends on concentration, immersion time and temperature. The BENZA is a better inhibitor than BENZA-TET. Polarization measurements showed that the inhibitor BENZA-TET is a cathodic type, but BENZA acts as a mixed type inhibitor. In addition, the changes in impedance parameters indicated that these compounds adsorbed on the metal surface leading to the formation of a protective film. Adsorption of benzamide derivatives on the mild steel surface was investigated to consider basic information on the interaction between the inhibitors and the metal surface. It was found to obey the Langmuir adsorption isotherm. From the temperature dependence, the activation energy in the presence of (BENZA) was found to be inferior to that in uninhibited medium. In order to explain why BENZA is the most efficient inhibitor, quantum chemical calculations were applied. The relationships between quantum chemical parameters and corrosion inhibition efficiency have been discussed to see if there is any correlation between them.     

Ultrasound irradiation in heterocycle synthesis: An overview

The synthesis of heterocyclic compounds has been a hot topic for several decades. Synthetic organic chemists are always in search of new methodologies which are greener for the synthesis of heterocyclic compounds. The ultrasound-assisted reactions have contributed much to this field. This review focuses on the impact of sonochemistry in the synthesis of heterocyclic compounds and covers the literature from 2009 to 2020.     

Synthesis and Biological Activity of Some Novel O-Phosphorylated Benzoxazole Derivatives

The phosphorylation of 2-(2′-hydroxyphenyl) benzoxazole has been accomplished with phosphorus oxychloride in a 1:1, 2:1, and 3:1 molar ratio in the presence of a base to yield O-phosphorylated benzoxazole derivatives. Their structures were confirmed by elemental analyses and IR, ¹H NMR, and ³¹P NMR spectral studies. These compounds have been screened for their insecticidal activity against Periplenata americana and were found to be quite active in this respect.