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 effic...

Efficient resolution of racemates chiral molecules is great significance in the pharmaceutical, agrochemical, fragrances, and food additives industries. Emerging homochiral porous materials such as metal–organic frameworks, covalent-organic porous-organic cages, metal-organic cages with ultrahigh surface area, controllable pore chemistry ample recognition sites are promising for efficient resol...

A normal-phase enantioselective high-performance liquid chromatographic method was developed for the enantiomeric resolution of naproxcinod, the most advanced cyclooxygenase-inhibiting nitric oxide donator of anti-inflammatory drugs designed for treatment of osteoarthritis. The enantiomers of naproxcinod were resolved on a Chiralpak AD-H (250 × 4.6 mm, 5 μm) column using a mobile phase system c...

The protein binding of non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac with human serum albumin (HSA) was investigated using indirect chiral high performance liquid chromatography (HPLC) and ultrafiltration techniques. S-(-)-1-(1-naphthyl)-ethylamine (S-NEA) was utilized as chiral derivatization reagent and pre-column derivatization RP-HPLC method was established for...

The study was designed to investigate some central effects of chiral xanthone derivatives [(R,S)-2-N-(6-chloro-2-xanthonemethyl)-amino-1-propanol - MH-31, R enantiomer - MH-32 and S enantiomer - MH-33] in mice. The effects of these chiral compounds were examined in picrotoxin-induced seizures, spontaneous locomotor activity and chimney tests. The tested compounds demonstrated variable influence...

The stereoselective toxicokinetics of ethofumesate enantiomers following a single intravenous (i.v.) administration at doses of 30 mg/kg were investigated in rabbits. Plasma concentrations of (+)- and (-)-ethofumesate were analyzed by a validated chiral HPLC method that involved extraction of plasma with organic solvent followed by separation on a cellulose-Tris-(3,5-dimethylphenylcarbamate)-ba...

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a designer drug commonly misused in large segments of young populations. MDMA is usually formulated in tablets of its racemate (1:1 mixture of its enantiomers) in doses ranging from 50 to 200 mg. MDMA has an enantioselective metabolism, the (S)-enantiomer being metabolized faster than the (R)-enantiomer. Different pharmacologic properties h...

Pregnane X receptor (PXR) is an orphan nuclear receptor that regulates the expression of genes encoding drug-metabolizing enzymes and transporters. In addition to affecting drug metabolism, potent and selective PXR agonists may also have therapeutic potential by removing endogenous and exogenous toxins. In this article, we report the synthesis and identification of novel PXR agonists from a lib...

ATP-dependent K(+) channels (K(ATP) channels) are composed of pore-forming subunits Kir6.x and sulfonylurea receptors (SURs). Cyanoguanidines such as pinacidil and P1075 bind to SUR and enhance MgATP binding to and hydrolysis by SUR, thereby opening K(ATP) channels. In the vasculature, openers of K(ATP) channels produce vasorelaxation. Some novel cyanoguanidines, however, selectively reverse op...

We investigated the enzyme kinetic basis for the stereoselective disposition of R- and S-omeprazole (OME) and racemic OME in human liver microsomes. OME is primarily metabolized by the hepatic cytochrome P450 enzyme system (CYP2C19 and 3A4). The metabolism of each enantiomer and pseudoracemic OME was studied using unlabeled and (13)C(7)-labeled enantiomers. The enantiomers inhibited each other'...