Enantiomers distomer

Although it might seem that adrninistration of enantiomericaHy pure substances would always be preferred, the diuretic indacrinone (3), is an example of a dmg for which one enantiomer mediates the harmful effects of the other enantiomer (4). (+)-Indacrinone, the diureticaHy active enantiomer or eutomer causes uric acid retention. Fortunately, the other enantiomer distomer) causes uric acid elimination. Thus, adrninistration of a mixture of the two enantiomers, although not necessarily racemic, may have therapeutic value. 

Dobutamine is structurally similar to dopamine but does not bind to dopamine receptors and is not associated with norepinephrine release from neurons. The drug exists as a racemic mixture, both isomers possesses p adrenergic effects, with the (+) enantiomer (eutomer) being 10 times more potent than the (-) enantiomer (distomer). Furthermore, the eutomer is a potent a adrenergic antagonist while the distomer is a potent... 

In the second scenario, target products and impurities are present in similar amounts. The separation of racemic mixtures exemplifies this scenario. The problem of racemic mixture formation often occurs during chemical synthesis, where 50% of the mixture consists of the wanted enantiomer (eutomer) and 50% is the unwanted enantiomer (distomer). In this case competitive adsorption and the elution order of the enantiomers are of special interest (Section 4.3.4). 

Stereoselectivity was defined by Rauws as follows Stereoselectivity is the extent to which an enzyme or other macromolecule, or macromolecular structure (antibody or receptor) exhibits affinity towards one molecule of a pair of isomers in comparison with and in contrast to the other isomer. . Lehmann has expressed this in a mathematical form the ratio of activity of the better fitting enantiomer (eutomer greek, eu = good), to that of the less fitting enantiomer (distomer greek, dys = bad) is defined eud-ismic ratio. From this an eudismic affinity quotient can be derived (Table 26.3). 

Members of the 2-APA class of NSAIDs have the potential for in vivo enantiomeric inversion, whereby the R-enantiomer (distomer) may be inverted to the active antipode, the S-enantiomer (eutomer). The S-enantiomer... 

MIP-CNTs nanocomposites are also proposed as innovative drug dehveiy devices (Yin et al., 2010). MIP nanotubes were fabricated by atom transfer radical polymerization (ATRP) and applied in enantioselective drug delivery and controlled release. Authors found that S-propranolol imprinted nanotubes provided differential release of enantiomers, whereby the release of the more therapeutically active S-propranolol (eutomer) is greatly promoted whilst the release of the less active R-enantiomer (distomer) is retarded. 

The two most important enzymatic approaches are enzymatic kinetic resolution by lipases or esterases (whole cells or purified enzymes) [9-18] and enzymatic asymmetrical synthesis by R- or 5-hydroxynitrile lyases (NHLs). Disadvantages of kinetic resolution are the need of separating the hydrolyzed product from its ester and the maximum theoretical yield of only 50%. In some cases it is possible to racemize the unwanted enantiomer (distomer) and recycle the racemate [19]. 

It is common to call the most active enantiomer eutomer and the less active one distomer. The ratio of the pharmacological activity of these are called the eudismic ratio (ER) and Pfeiffer s mle states that the lower the effective dose of a drug the greater the difference in the pharmacological effect of the optical isomers . When two enantiometic... 

Lehman et al. (1986) stated the definitions of stereoselectivity in the following manner the better fitting enantiomer (the one with higher affinity for the receptor) is called the eutomer, whereas the one with the lower affinity is called the distomer. The ratio of... 

In a series of agonists and antagonists (for definitions, see section 2.4), the eudismic affinity quotient can also he defined as a measure of stereoselectivity. Because of widespread misconceptions, the distomer of a racemate is often considered inactive and of no consequence to pharmacological activity, an idea reinforced by the fact that resolution (i.e., separation) of racemates is economically disadvantageous. In the 1980s, Ariens and his associates (Ariens et al., 1983 Ariens, 1984, 1986) published a series of influential books and papers that showed the fallacy of this concept and pointed out the necessity of using pure enantiomers in therapy and research thankfully, this message has now been learned. 

However, there are instances in which the use of a racemate has advantages sometimes it is more potent than either of the enantiomers used separately (e.g., the antihistamine isothipendyl), or the distomer is converted into the eutomer in vivo (the anti-inflammatory... 

The more active isomer (where activity refers to binding affinity at a defined receptor) is designated the eutomer, the less active is the distomer. The ratio of activities is the eudismic ratio, and its logarithm, the eudismic index, is then proportional to the difference in binding free energy between the enantiomers. The eudismic index is a quantitative measure of chiral discrimination. 

Enantiomeric purity, measured as the enantiomeric excess (ee) of an isomer, is determined by the formula (% major isomer)—(% minor isomer). Thus, if a chiral drag is said to be or 50% ee, the composite mixture contains 75% of one enantiomer and 25% of the other. Enantioselectivity refers to the greater activity of one enantiomer over its minor image. Enantiospecificily is rarely observed and implies that one enantiomer possesses 100% of the observed activity in most cases it is more accurate to use the term highly enantioselective. The pharmacologically more active enantiomer is termed the eulomei and the less active enantiomer is referred to as tire distomer. 

As can be seen from Figure 2, the (/ )-enantiomers (eutomers) of the silanols 3 and 7 show a significantly higher affinity for muscarinic M2 and M3 receptors than the corresponding (S)-antipodes (distomers). To the best of our knowledge, this is the first example of a biological discrimination between enantiomeric silicon compounds, with the silicon atom as the center of chirality. The stereoselectivity indices SI [SI = Kn S)/Kd(R) for sila-procyclidine (3) are 1.8 (M2) and 4.1 (M3), respectively. For sila-tricyclamol iodide... 

In a nonchiral environment, the enantiomers of a racemate possess the same physical and chemical properties. But in the early 1930s, Easson and Stedman introduced a three-point attachment model that laid the basis for the initial understanding of stereochemical differences in pharmacological activity [13]. The authors described the differences in the bioaffinity of the enantiomers to a common site on an enzyme or receptor surface, with the receptor or enzyme needing to possess three nonequivalent binding sites to discriminate between the enantiomers. The enantiomer that interacts simultaneously with all three sites is called the eutomer (active enantiomer), whereas the other, which binds to fewer than three sites at the same time, is called the distomer (inactive enantiomer) [14]. 

Atropine is the racemic mixture of R- and S-hyoscyamine produced during the pharmaceutical plant extraction process. R-hyoscyamine is nearly inactive on MR (distomer) whereas S-hyoscyamine exhibits high affinity (eutomer). Nevertheless, due to economic reasons atropine is typically administered even though only half of the applied dose (S-hyoscyamine) is pharmacologically active on MR. Surprisingly, there is still little information about different pharmacokinetic behaviour of both enantiomers anyhow [46,47],... 

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