Barbiturates chemical properties

Early investigators adduced various kinds of chemical evidence in support of a monohydroxy-dioxo structure for barbituric acid (112) (a) reaction with diazomethane afforded a mono-O-methyl deriva- iye,i59,i6o barbituric acid and its 5-alkyl derivatives are much stronger acids than the 5,5-dialkyl derivatives, and (c) the 5-bromo and 5,5-dibromo derivatives have different chemical properties. - The early physical evidence also appeared to substantiate the monoenol structure, this formulation having been suggested for barbituric acid in 1926 on the basis of its ultraviolet spectrum and again in 1934, In the 1940 s, ultraviolet spectroscopic studies led to the suggestion of other monohydroxy and dihydroxy structures for barbituric acid, whereas its monoanion was assigned structure 113 (a clear distinction between ionization and tautomerism was not made in these papers). 

R. Prankerd and R. McKeown, Physico-chemical properties of barbituric acid derivatives. Part 1. Solubility-temperature dependence for 5,5-disubstituted barbituric acids in aqueous solutions, Int.. Pharm., 1990,62(1), 37-52. 

Pharmacology Zolpidem is a nonbenzodiazepine hypnotic. While zolpidem is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with a GABA-BZ receptor complex and shares some of the pharmacological properties of the benzodiazepines. 

Pharmacoiogy Zaleplon is a nonbenzodiazepine hypnotic. Zaleplon has a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties. 

Nonbarbiturate sedative-hypnotics. Nonbarbiturate sedative-hypnotics are drugs with chemical or physiological properties similar to barbiturates and are considered barbiturate-like substances. These drugs include ... 

Theoretically, the purine- and pyrimidine-based nucleic acid constituents and the barbiturates have the potential to occur in several tautomeric forms of the keto/ enol and amino/imino type where the aromatic character of the six-membered pyrimidine ring is fully or, as in the barbiturates, partially retained, as illustrated in Fig. 15.4. In these molecular species, which are all feasible on the basis of organic chemical considerations, the hydrogen-bonding donor/acceptor properties of the functional amino, imino, enol and keto groups vary considerably, being donor in one form and acceptor in the other. 

When it comes to physicochemical (biological) properties the common structural formulae obscure rather than explain the problem. One of the most convincing examples may be the anaesthetic activity of chemicals. Among general anaesthetics one can identify such diverse chemical families like hydrocarbons, alcohols, ethers, barbiturates, nitrous oxide, steroids, etc. Each one must have anaesthetic activity encoded in its structure but how is it discovered using conventional chemical symbolic The planar or three-dimensional chemical notation can be an obstacle to making a breakthrough in chemistry. 

The barbitmates are the other major group of sedative-hypnotic agents. Similar to the benzodiazepines, they are a group of chemically related drugs and there are many variations in properties, particularly onset of effects and duration of action. The most recognized effects of the barbiturates are centrally mediated and include sedation, hypnosis, decreased anxiety, and, at high doses, anesthetic properties. The mechanism of... 

A large proportion of drug substances, whether neutral molecules, free adds, free bases or salts, are capable of exhibiting polymorphism or pseudopolymorphism (hydrate or solvate formation). It has been reported that 70% of barbiturates, 60% of sulfonamides and 23% of steroids exhibit polymorphism." Polymorphism often influences a range of physicochemical properties such as solubility, dissolution rate, stability and powder properties as well as bioavailability. Usually, it is possible to determine the most stable polymorph and discover recrystallization solvents that uniquely produce this form and improve the physicochemical and physicome-chanical properties and chemical stability of the drug. 

The Hammett-type correlation for the rate constants of 5-allyl-5-R-barbiturates has been reported by Carstensen et al. and suggested for use in stability predictions.569 Similar correlations were also found for the hydrolysis of 5-arylidenebarbituric acids.363,567 Linear free energy relationships have also been reported for dissociation constants,45,51 polarographic half-wave potentials,570 fluorescence70 and luminescence phenomena,71 and 13C-NMR chemical shifts129 for different classes of barbituric acid derivatives. Application of the dual substituent parameters method in LFER analysis of barbiturates, using Taft s polar and steric constants for various chemical and physicochemical properties, was also evaluated.571... 

Structural features of the barbiturate molecule which are required for its hypnotic, convulsant, and/or anticonvulsant properties have been summarized by Vida and Gerry,381 and numerous studies were devoted to physiological effects and pharmacological mechanisms of action of barbiturates in relation to chemical and stereochemical factors. Some recent articles and reviews are suggested on this fascinating and still incompletely elucidated subject.382 Clearly, the history of barbiturates383 has many paragraphs yet to be written. 

It has been observed that the sodium barbiturates , in general, exhibit extremely lipophilic property that may cause distinct and rapid chemical incompatibility reactions, such as precipitation, when such compoimds are inadvertently brought in contact with the acid salts of relatively weak basic amines. 

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