Although Michael acceptors display a potent and broad spectrum of bioactivity, they have largely been ignored in drug discovery because of their presumed indiscriminate reactivity. As such, a dearth of information exists relevant to the thiol reactivity of natural products and their analogues possessing this moiety. In the midst of recently approved acrylamide-containing drugs, it is clear that a good understanding of the hetero-Michael addition reaction and the relative reactivities of biological thiols with Michael acceptors under physiological conditions is needed for the design and use of these compounds as biological tools and potential therapeutics. This Perspective provides information that will contribute to this understanding, such as kinetics of thiol addition reactions, bioactivities, as well as steric and electronic factors that influence the electrophilicity and reversibility of Michael acceptors. This Perspective is focused on α,β-unsaturated carbonyls given their preponderance in bioactive ...

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Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions

Cyclopropane amino acids: 2,3- and 3,4-Methanoamino acids

Publisher Summary This chapter discusses the use of pyrazole as antioxidants in motor fuels, medicine, and development of cine-film. Besides the traditional interest in pyrazole derivatives which have been the basis of numerous dyes and drugs, a number of pyrazole anesthetics have appeared. Recent studies have established that pyrazolines are intermediates in the synthesis of cyclopropanes; they act as effective chemical bleaching agents, and as a constituent of luminescent and fluorescent substances. Pyrazoles are stable compounds with relatively high boiling points. It is a colorless compound with a peculiarly penetrating sweetish smell. The introduction of substituents in the 3-, 4-, and 5-positions causes an increase in the boiling point, which is expected with increased molecular weight, but the boiling point falls sharply with substitution in the 1-position. Similarly, 1-substituted pyrazoles melt at temperatures significantly lower than the corresponding compounds with free N-H groups. Both of these anomalies are due to the particularly strong association of pyrazoles unsubstituted in position 1, as proved by cryoscopic determination, spectral studies, dipole moment measurement, and infrared spectroscopy.

Progress in Pyrazole Chemistry

This invention provides aryl and heteroaryl compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention may be antagonists, or partial antagonist of factor IX and/or factor XI and thus, may be useful for inhibiting the intrinsic pathway of blood coagulation. The compounds may be useful in a variety of applications including the management, treatment and/or control of diseases caused in part by the intrinsic clotting pathway..

Aryl and heteroaryl compounds, compositions, and methods of use

Publisher Summary This chapter reviews the chemistry of hydantoins. The hydantoins can be synthesized using amino acids, cyanate or thiocyanate salts, alkyl or aryl isocyanates and isothiocyanates, ureas, α-dicarbonyl compounds, Bucherer–Bergs and Read reactions, and cycloaddition reactions with heterocumulenes. The chapter also illustrates physicochemical studies on hydantoins. H-NMR, IR, and UV techniques are widely used to study ionization and tautomerism in hydantoins. Hydantoins are weak acids which owe their acidic character to dissociation of the proton bonded to the 3-nitrogen atom as this allows for maximum delocalization of charge in anion. The chapter also presents physicochemical studies on hydantoins using ultraviolet spectroscopy, mass spectrometry, infrared spectroscopy, nuclear magnetic resonance spectroscopy, crystal structure determinations, and quantum mechanical calculations. The reactivity of hydantoins and their derivatives are described further in the chapter. Hydantoins and thiohydantoins can react with nucleophilic and electrophilic as well as with other types of reagents. On protonation in a strongly acidic solution, hydantoin cations are formed. Hydantoins can easily be alkylated in the N-3 position by treatment with alkyl halides in an alkaline solution in protic or aprotic solvents. Other alkylating agents include dimethyl sulfate and diazomethane.

Abdel Hamid Harhash

Papers

Reactivity of unsaturated centres in heterocycles and chalkones toward diazoalkanes

Reactions with 1(2H)-phthalazinones, 4,5-dihydro-3(2H)-pyridazinones and 3-pyrazolin-5-ones

Photochemical Addition and Photochemical Dehydrogenation Reactions in Sunlight

Das Verhalten von Oxazolinonen‐(5) und Thiazolinonen‐(5) gegen N‐Phenyl‐hydroxylamin und Phenylhydrazin

Reaktionen mit Δ2-Thiazolinonen-(5), II. Umlagerung von 4-Arylazo-2-benzylmercapto-Δ2-thiazolinonen-(5) in 1.2.4-Triazol-Derivate