Exploiting the Power of Stereochemistry in Drugs: An Overview of Racemic and Enantiopure Drugs

Abstract

Stereochemistry is one of the essential dimensions in pharmacology as it dictates how enantiomers interact with biological systems. Chirality is very important in drug design. Enantiomers of the same chiral drug can have different pharmacodynamic and/or pharmacokinetic properties. In this context, replacing some existing racemates with single isomers has resulted in improved safety and/or efficacy profile of various racemates. Single enantiomer drug use can potentially lead to simpler and more selective pharmacologic profiles, improved therapeutic indices, simpler pharmacokinetics due to different rates of metabolism of the different enantiomers, decreased drug interactions, and drug companies are increasingly using chiral switching as a marketing strategy. Additionally, due to different pharmacological activity, enantiomers of chiral drugs can differ in toxicity. However, unpredicted toxicity has been reported in some chiral switching cases which has resulted the withdrawal of the enantiomer from the market or a halt in its development. In view of above, before switching to single enantiomer drugs, prescribers should look for evidence from well-conducted clinical trials to prove that the chiral switch is cost-effective and improves the outcomes for patients rather than patents. The U.S. Food and Drug Administration (FDA) have allowed single enantiomers of generic drugs to be patented and marketed under different name. FDA regulations require that all chiral bioactive drug molecules must be isolated and tested for the efficacy and safety, and have to be as pure as possible containing a single pure enantiomer.

Preparation and Reactions of Certain Racemic and Optically Active Cyanohydrins Derived from 2-Chlorobenzaldehyde, 4-Fluorobenzaldehyde, Benzo[d][1,3]-dioxole-5-carbaldehyde and 2,3-Dihydrobenzo[b][1,4]dioxine-6-carbaldehyde. Antimicrobial and in vitro Antitumor Evaluation of the Products

“…Co mpound (R,2S)-6a is inactive against the four bacterial species, meanwhile its diastereomeric mixtu re analog (R,2S)(S,2S)-6a showed slight activity against Bacillus subtilis (Gram +ve) and Escherichia coli (Gramve) bacterial species. This might reflect the well established relation between the stereochemistry of a g iven compound and its biological act ivity [24][25][26][27]. On the other hand, all the investigated compounds did not exert any activity against the two fungal species Aspergillus flavus and Candida albicans.…”

“…This approach is rather decisive, clean and cheap [5,[20][21][22][23]. The increasing interest in synthesizing optically pure compounds is due to the well established correlation between the biological act ivity and stereochemical aspects [24][25][26][27]. Thus, the present work aims at preparing optically act ive cyanohydrins as well as their racemic analogous derived fro m 2-chlorobenzaldehyde (1a), 4-fluorobenzaldehyde (1b), ben zo[d] [1,3] dio xo le-5-carbaldehyde (piperonal, heliotropine) (1c) and 2,3 -dihydrobenzo[b] [1,4] dio xine-6-carbaldehyde (1d) as well as studying their acid hydrolysis, reduction and derivatization with (S)-napro xen chloride (S)-5.…”

The synthesis and characterization of novel brush-type chiral stationary phase based on terpenoid selector for resolution of chiral drugs

“…The organic solvent was removed on a rotary evaporator in vacuo to give a crude product of 4′-carboxyl-1′-ursolic methyl ester-3β-yl-benzoate, which was subjected to silica gel column separation eluting with dichloromethane/acetic acid (100/1, v/v). This new terpenoid chiral selector was white solid with a yield of 82%, which was characterized by HPLC, 1 …”

“…Usually, the enantiomers of these bioactive molecules exhibit different physiological effects following different pathways in biological processes. The development of enantiopure drugs resulted in significant improvement in the remedies available for the treatment of various severe sicknesses [1]. As a result, the enantiomeric separation of chiral pharmaceuticals has become an increasingly interesting and important unit operation in the pharmaceutical industry [2].…”

Development of a UPLC method with Chiral Derivatization for the Determination of Atenolol and Metoprolol Enantiomers in Tablet Preparations

“…Liquid chromatography is now the most accepted method for chiral separations, not only in the direct way, using chiral stationary phases, but also in the indirect way, using chiral derivatizing reagents [2][3][4] . Dinitrophenyl ether β-cyclodextrin-bonded chiralstationary phase (CSP) was used for direct enantiomeric resolution of atenolol by Cheng et al (2014); Baranowska (2015) determined metoprolol isomers and its metabolites using a Chiralcel OD-RH column packed with cellulose tris-(3,5-dimethylphenylcarbamate) stationary phase 5,6 .…”