Rizk E. Khidre

Synthesis and anti-microbial activity of some 1- substituted amino-4,6-dimethyl-2-oxo-pyridine-3-carbonitrile derivatives.

A new series of 1- substituted amino-4,6-dimethyl-2-oxo-pyridine-3-carbonitrile such as hydrazide hydrazones 3a-h; ethane-1,2-diaminopyridine 6; phthalimidopyridines 8a,b; hydrazides 10a,b; urea 11a and thiourea 11b were synthesized in a good to excellent yield in step efficient process, using 1-amino-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (1) as a key intermediate. The antibacterial and antifungal activities of the synthesized compounds were evaluated. The obtained data indicated that the majority of the tested compounds exhibited both antibacterial and antifungal activities, particularly compounds 8a and 8b showed a comparable effect to a well known antibacterial and antifungal agents.

Elaborating on efficient anti-proliferation agents of cancer cells and anti-inflammatory-based N-bisphosphonic acids.

Methylenebisphosponic acid tetraethyl ester (1) was added to 2‐azido‐7a–e and 2‐chloroquinoline‐3‐chalcones 10a–e in boiling sodium ethanolate solution to give, via Michael addition, tetrazolo[1,5‐a]quinoline‐8a–d, 13a and 2‐chloroquinoline‐based bisphosphonates 11a–d, 14a in E‐configuration. Further acid hydrolysis afforded the respective BP‐acid analogues E‐9a–d, 12a–d, 13b, and 14b in excellent yields. Anti‐tumor activity screening for the new BP‐acids at a dose of 10 µM utilizing 44 different human tumor cell lines representing breast, ovary, prostate, lung, and CNS cancer as well as leukemia and melanoma was carried out. Eight of ten tested compounds exhibited remarkable anti‐tumor activity against breast and prostate cancer, and a promising anti‐tumor sensitivity toward ovarian cancer and melanoma. Conversely, there was only scattered activity against leukemia and no noticeable action of these BP‐acids on CNS or lung cancer. Based on the prediction results (PASS program), anti‐inflammatory activity of the new acids was also determined in vivo, by the acute carrageenin induced paw edema in rats. Many of these compounds showed anti‐inflammatory properties at a dose of 50 mg/kg body weight.

Synthesis of 5‐ and 6‐N‐heterocyclic Methylenebisphosphonate Derivatives and Evaluation of their Cytogenetic Activity in Normal Human Lymphocyte Cultures

Methods for the preparation of various aminomethylene bisphosphonates were developed. The required bisphosphonates were obtained by applying tetraethyl methylenebisphosphonate reagent to different types of oxazinones and the relevant Schiff base derivatives. Based on the prediction results (Pass program), we further estimated the sister chromatid exchange frequency and proliferation rate index values of human lymphocyte cultures after the administration of four newly synthesized bisphosphonates in order to evaluate their cytotoxic/cytostatic and possible antineoplastic potency. The results showed that all four bisphosphonates cause a dose‐dependent increase in sister chromatid exchange frequency, followed by a decrease in proliferation rate index in both experiments compared to the control.

Application of Benzoylaceteonitrile in the Synthesis of Pyridines Derivatives

This review deals with synthetic potential and utility of benzoylacetonitrile in the synthesis of pyridine derivatives. The reac- tions are subdivided into groups that cover the synthetic methods of pyridine derivatives from benzoylacetonitrile e.g. self condensation, Friedlander reaction, Michael Addition reaction, addition to enaminones, reaction with enamino-nitriles or enamino-esters, and one-pot three component reactions. A brief account on the synthesis of benzoylacetonitrile was also displayed.

2-Chloroquinoline-3-carbaldehyde II: Synthesis, Reactions, and Applications

This review deals with synthesis and reactions of 2-chloroquinoline-3-carbaldehyde during the period from 1979 to 1999. The reactions are subdivided in groups that cover the reactions of chloro- and aldehyde substituent as well as reactions which involve both groups. Some of these reactions have been applied successfully to synthesis of biologically important compounds. The main purpose of this review is to present a survey of the literature on 2-chloroquinoline-3-carbaldehyde chemistry and provide useful and up-to-date data for organic and medicinal chemist since such compound has not been previously reviewed in this period.

Regioselective Condensation of Alkylidenephosphoranes to N-Methoxy- and N-Anilino-1H isoindole-1,3-(2H)-diones

Abstract Treatment of 2-methoxyisoindoline-1,3-dione with resonance-stabilized alkylidenephosphoranes afforded the corresponding monoalkenes as the sole reaction product, in ∼58–63% yields, whereas more than 80% yields of the same monoolefin products were obtained when the reactions were carried out under microwave conditions. Similarly, 2-(phenylamino)isoindoline-1,3-dione reacted under either thermal or microwave conditions to give only the corresponding monoalkene derivatives. The alkene products from both substrates were further reduced to the corresponding isoindoles using Zn-dust in EtOH. Prediction of the designed compounds and the in vivo anti-inflammation activity of the products in the rat adjuvant model were also studied. The work is the first demonstration of the anti-inflammatory activity of phthalimide derivatives. GRAPHICAL ABSTRACT

Overview of the Chemical Reactivity of Phosphonyl Carbanions Toward Some Carbon-Nitrogen Systems

This review summarizes research results concerning the reactions of phosphonyl carbanions with different carbon-nitrogen systems, amines, amides, imines, oximes, hydrazones, nitriles, diazo compounds, isocyanates, and azides, reported by us and other re- search group over the last years. It outlines the utility of such reactions in various aspects of heterocyclic chemistry. Some of these reac- tions have been applied successfully to the synthesis of biologically important compounds. A brief account on the synthesis of Horner reagents was also displayed.

New Potential Antimalarial Agents: Design, Synthesis and Biological Evaluation of Some Novel Quinoline Derivatives as Antimalarial Agents.

A novel series of dihydropyrimidines (DHPMs) 4a–j; 2-oxopyran-3-carboxylate 7a,b; 1-amino-1,2-dihydropyridine-3-carboxylate 8; and 1,3,4-oxadiazole derivatives 12 with quinolinyl residues have been synthesized in fairly good yields. The structure of the newly synthesized compounds was elucidated on the basis of analytical and spectral analyses. In vitro antimalarial evaluation of the synthesized quinoline derivatives against Plasmodium falciparum revealed them to possess moderate to high antimalarial activities, with IC50 values ranging from 0.014–5.87 μg/mL. Compounds 4b,g,i and 12 showed excellent antimalarial activity against to Plasmodium falciparum compared with the antimalarial agent chloroquine (CQ).

Production of pyrans, pyridazines, pyrimidines, pyrazines and triazine compounds using benzoylacetonitriles as a precursor

Benzoylacetonitriles are easily available and have high chemical reactivity due to the presence of three active moieties; nitrile, carbonyl, and active methylene functions. This review article represents a survey covering the synthetic strategies leading to five six-membered heterocycles; pyrans, pyridazines, pyrimidines, pyrazines, and triazine compounds; utilizing benzoylacetonitriles as starting precursor since 1985. The reactions are subdivided into groups that cover the synthetic methods of these heterocycles.

Synthetic routes to imidazothiazines

GRAPHICAL ABSTRACT Abstract This review article presents the available synthetic routes for the preparation of different types of imidazothiazines. Imidazothiazines dealt with are classified into five types based on the position of linkage between imidazole and thiazine rings. The importance of the latter compounds in pharmacology is also discussed. The main purpose of this review is to present a survey of literature on imidazothiazines and provide useful and up-to-date data to organic and medicinal chemist, since such compounds have not been reviewed before.