Beta-turn mimic in tripeptide with Phe(1)-Aib(2) as corner residues and beta-strand structure in an isomeric tripeptide: an X-ray diffraction study

A single crystal X-ray diffraction study of the tripeptide Boc-Phe-Aib-Leu-OMe (Aib = alpha-aminoisobutyric acid) reveals that it forms structurally one of the best type II beta-turns so far reported in tripeptides, stabilized by 10 atom intramolecular hydrogen bonding. In contrast, the isomeric tripeptide Boc-Phe-Leu-Aib-OMe adopts a beta-strand like conformation. Interestingly, a previously reported structure of another isomeric tripeptide, Boc-Leu-Aib-Phe-OMe, shows a double bend conformation without any intramolecular hydrogen bonding. These results demonstrate an example of the creation of structural diversities in the backbone of small peptides depending upon the co-operative steric interactions amongst the amino acid residues.     

LC–MS Simultaneous Determination of Itopride Hydrochloride and Domperidone in Human Plasma

A rapid, simple, sensitive and specific liquid chromatography–tandem mass spectrometry method was developed and validated for simultaneous quantification of itopride hydrochloride and domperidone in human plasma. Both drugs were extracted by liquid–liquid extraction with ethyl acetate and saturated borax solution. The chromatographic separation was performed on a reversed-phase C18 column with a mobile phase of water–methanol (2:98, v/v) containing 0.5% formic acid. The protonated analyte was quantitated in positive ionization by multiple reaction monitoring with a mass spectrometer. The assay exhibited linearity over the concentration range of 3.33–500 ng mL⁻¹ for itopride hydrochloride and 3.33–100 ng mL⁻¹ for domperidone in human plasma. The precursor to product ion transitions of m/z 359.1–72.3 and 426.0–147.2 were used to measure itopride hydrochloride and domperidone respectively. The method was found suitable for the analysis of plasma samples collected during phase 1 pharmacokinetics study of itopride HCl 50 mg and domperidone 20 mg in 12 healthy volunteers after single oral doses of the combination drug.

     

Synthesis of different isoindolone embedded heterocycles with phenolic subunits from a common intermediate, 3-(2′-hydroxyaroyl)-2,3-dihydroisoindol-1-ones

A series of biologically important isoindolone embedded heterocycles such as tetracyclic 2,4-diamino-5-aryl-10-oxo-10H-1,10a-diazaindeno[2,1-a]indene-3-carbonitriles and tricyclic 1-aryl-3,5-dioxo-1H-imidazo-[3,4-b]isoindoles have been synthesized from an easily derived common intermediate, 3-(2′-hydroxyaroyl)-2,3-dihydroisoindol-1-ones. The significant advantages of the present methodologies are the use of simple and easily available starting materials and reagents, operational simplicity, and good yields of the products with high atom-economy.