This study investigated the relative contribution of ion-trapping, microsomal binding, and distribution of unbound drug as determinants in the hepatic retention of basic drugs in the isolated perfused rat liver. The ionophore monensin was used to abolish the vesicular proton gradient and thus allow an estimation of ion-trapping by acidic hepatic vesicles of cationic drugs. In vitro microsomal s...

Lipophilicity, as one of the most important physicochemical parameters of bioactive molecules, was investigated for twenty-two thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azoles. The determination was carried out by reversed-phase thin-layer chromatography, using a binary isopropanol-water mobile phase. Chromatographically obtained lipophilicity parameters were correlated with calculate...

Lipophilicity (logP) represents one of the most studied and most frequently used fundamental physicochemical properties. At present there are several possibilities for its quantitative expression and many of them stems from chromatographic experiments. Numerous attempts have been made to compare different computational methods, chromatographic methods vs. computational approaches, as well as ch...

In order to investigate structure-activity relationships between antimycobacterial activities and basic substituents at the C-10 position of levofloxacin (LVFX), we synthesized a series of pyridobenzoxazine derivatives by replacement of the N-methylpiperazinyl group of LVFX with various basic substituents. A compound with a 3-aminopyrrolidinyl group had one-half the activity of LVFX against Myc...

In this study, the existence of biological potential of selected N-(substituted phenyl)-2-chloroacetamides was examined none empirically, as was the possibility of applying simpleexperimental technique in predicting essential properties which affect the biological activityof the compounds. By applying the Lipinski and Ghose’s rules, it has been revealed that theexamined chloroacetamides fulfill...

In this assay, the evaluation of lipophilicity of four ACE-inhibitors and hydrochlorothiazide (HCTZ) with RP-TLC on cellulose layers was described using three binary solvent systems. The selected ACE inhibitors had sufficiently different structures which can indicate the method suitability for their lipophilicity evaluation as the model substances in comparison with HCTZ. In addition, the linea...

Abstract Antipsychotic drugs are commonly prescribed for different mental disorders and can be classified into two main groups: the first which contain originally developed antipsychotics of generation or typical other group with newly atypical second generation. In this study, eleven antipsychotic (chlorpromazine, flupentixol, haloperidol, zuclopenthixol, aripiprazole, clozapine, olanzapine, q...

Two series of phthalimides--one possessing an N-phenoxyalkyl moiety substituted at position 3 or 4 of the phenyl ring (1-9) and the other of N-alkenyl or alkinyl phthalimides (10-18)--were synthesized, evaluated for anticonvulsant activity and had their in silico lipophilicity estimated using computer programs. The anticonvulsant activity of phthalimides containing an unsaturated substituent at...

O-GlcNAcase (OGA) has received increasing attention as an attractive therapeutic target for tau-mediated neurodegenerative disorders; however, its role in these pathologies remains unclear. Therefore, potent chemical tools with favorable pharmacokinetic profiles are desirable to characterize this enzyme. Herein, we report the discovery of a and novel OGA inhibitor, compound 5i, comprising amino...

The replacement of oxygenated functionality (hydroxy and alkoxy) with a fluorine atom is commonly used bioisosteric in medicinal chemistry. In this paper, we use molecular matched-pair analysis to better understand the effects on lipophilicity. It seems that reduced log P compound normally dominant determining size difference. We observe presence additional electron-donating groups an aromatic ...