There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles.

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Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine's Tool Box.

Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Heterocyclic compounds and uses thereof

Nitrogen‐, and/or Sulfur-Containing Heterocyclic Rings Poulomi Majumdar,†,‡ Anita Pati,†,§ Manabendra Patra, Rajani Kanta Behera,† and Ajaya Kumar Behera*,† †Organic Synthesis Laboratory, School of Chemistry, Sambalpur University, Jyoti Vihar, Burla 768019, Orissa, India ‡State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, P.R. China School of Applied Sciences (Chemistry), KIIT University, Bhubaneswar 751024, India National Institute of Science & Technology, Palur Hill, Berhampur 761068, Orissa, India

Acid hydrazides, potent reagents for synthesis of oxygen-, nitrogen-, and/or sulfur-containing heterocyclic rings.

Pyrazole, pyrazolone and enaminonitrile pyrazole derivatives: Synthesis, characterization and potential in corrosion inhibition and antimicrobial applications

Aiming for the synthesis of new heterocyclic compounds containing a sulfonamido moiety suitable for use as antibacterial agents, the precursor ethyl {[4-N-(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenylazo}cyanoacetate was reacted with a variety of active methylene compounds producing pyran, pyridine and pyridazine derivatives. Also, the reactivity of the precursor hydrazone towards hydrazine derivatives to give pyrazole and oxazole derivatives was studied. On the other hand, treatment of the same precursor with urea, thiourea and/or guanidine hydrochloride furnished pyrimidine and thiazine derivatives, respectively. The newly synthesized compounds were tested for antibacterial activity, whereby eight compounds were found to have high activities.

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Synthesis and antibacterial evaluation of novel heterocyclic compounds containing a sulfonamido moiety.

5-(p-Anisyl)-2-methyl-7-(p-tolyl)-4H-pyrido[2,3-d][1,3]oxazin-4-one (III) was prepared. The reactivity of III towards nucleophilic reagents was investigated. 5-(p-Anisyl)-2-methyl-7-(p-tolyl)-4H-pyrido[2,3-d] pyrimidin-4-one(VI) was synthesised from III by the action of ammonium acetate and zinc chloride. The structure of VI was chemically confirmed by reactions with acetic anhydride, benzoyl chloride, chloroacetic acid, methyl iodide, dimethyl sulphate and ethyl bromoacetate. Compound (VI) reacted with secondary and primary amines under Mannich conditions to afford 5-(p-anisyl)-2-methyl-3-methylene substituted amino-7-(p-tolyl)- 4H-pyrido[2,3-d]pyrimidin-4-ones (XIV) and (XV), respectively. Thiation of VI gave the thione 5-(p-anisyl)-2-methyl-7-(p-tolyl)-4H-pyrido [2,3-d]pyrimidin-4-thione (XIX)

Reactions of 5-(p-Anisyl)-2-methyl-7-(p-tolyl)-4H-pyrido[2,3-d][1,3]oxazin-4-one

A new series of 5-(3,5-dinitrophenyl)-1,3,4-thiadiazole derivatives were prepared and evaluated for their in vitro antimicrobial, antitumor, and DHFR inhibition activity. Compounds 9, 10, 13, and 16 showed strong and broad-spectrum antimicrobial activity comparable to Amoxicillin and Fluconazole as positive antibiotic and antifungal controls, respectively. Compounds 6, 14, and 15 exhibited antitumor activity against four human cancer cell lines, CCRF-CEM leukemia, HCT-15 colon, PC-3 prostate, and UACC-257 melanoma cell lines using Doxorubicin as a reference drug. Compounds 10, 13, 14, and 15 proved to be the most active DHFR inhibitors with an IC50 range of 0.04 ± 0.82–1.00 ± 0.85 µM, in comparison with Methotrexate (IC50 = 0.14 ± 1.38 µM). The highly potent DHFR inhibitors shared a similar molecular docking mode and made a critical hydrogen bond and arene‒arene interactions via Ser59 and Phe31 amino acid residues, respectively.

https://www.mdpi.com/1420-3049/24/6/1066/pdf

Design, Synthesis, and Molecular Docking Study of Novel Heterocycles Incorporating 1,3,4-Thiadiazole Moiety as Potential Antimicrobial and Anticancer Agents

Benzoxazinones and quinazolinones have a wide spectrum of biological activity. In this paper we focused on studying the antimicrobial and anti-inflammatory activities of some newly synthesized benzoxazinone and quinazolinone derivatives. Thus we prepared 2-[α-benzoylaminostyryl]-6,8-dibromo-3,1-benzoxazin-4(H)-one 2 which underwent a reaction with primary and secondary amines, and hydrazine hydrate to give compounds 3, 4 and 5, respectively. Treatment of 2 with hydroxylamine hydrochloride, formamide and/or NaN3/AcOH afforded compounds 7, 8, 11 and 12, respectively. Also, compound 2 reacted with maleic anhydride, aromatic hydrocarbons and/or active methylene compounds to produce compounds 13, 15a-c and 16, respectively. Most of the newly synthesized compounds showed significant antimicrobial and anti-inflammatory activities comparable to ampicillin, mycostatine and indomethacin positive controls.

Mohammad E. Azab

Papers

Pyrazole, pyrazolone and enaminonitrile pyrazole derivatives: Synthesis, characterization and potential in corrosion inhibition and antimicrobial applications

Synthesis and antibacterial evaluation of novel heterocyclic compounds containing a sulfonamido moiety.

Reactions of 5-(p-Anisyl)-2-methyl-7-(p-tolyl)-4H-pyrido[2,3-d][1,3]oxazin-4-one

Design, Synthesis, and Molecular Docking Study of Novel Heterocycles Incorporating 1,3,4-Thiadiazole Moiety as Potential Antimicrobial and Anticancer Agents

Synthesis, Antimicrobial and Anti-inflammatory Activity of Some New Benzoxazinone and Quinazolinone Candidates.