Search results for "lääkekemia"
showing 9 items of 9 documents
Liquid chromatography in pharmaceutical analytics
2017
Tutkielmassa perehdytään nestekromatografian käyttöön lääkeaineanalytiikassa. Korkean erotuskyvyn nestekromatografia (HPLC) on suosittu menetelmä lääkeaineiden analysoinneissa, esimerkiksi pitoisuuksien tai epäpuhtauksien määrityksissä. HPLC-menetelmät voidaan luokitella useisiin alalajeihin ja käänteisfaasinestekromatografia (RP-HPLC) on niistä suosituin lääkeaineanalytiikassa. Tässä kirjallisuuskatsauksessa käsitellään erityisesti nopeaa nestekromatografiaa. Analyysimenetelmiä voidaan nopeuttaa sopivan kolonnin avulla. Tavanomainen HPLC-ajo on mahdollista toteuttaa lyhyemmässä ajassa käyttämällä lyhyttä kolonnia tai kolonnia, jossa partikkelikoko on pieni. Kuitenkin tehokkain tapa on käyt…
Development of new Coumarin-based profluorescent substrates for human cytochrome P450 enzymes
2018
Cytochrome P450 (CYP) enzymes constitute an essential xenobiotic metabolizing system that regulates the elimination of lipophilic compounds from the body. Convenient and affordable assays for CYP enzymes are important for assessing these metabolic pathways.In this study, 10 novel profluorescent coumarin derivatives with various substitutions at carbons 3, 6 and 7 were developed. Molecular modeling indicated that 3-phenylcoumarin offers an excellent scaffold for the development of selective substrate compounds for various human CYP forms, as they could be metabolized to fluorescent 7-hydroxycoumarin derivatives. Oxidation of profluorescent coumarin derivatives to fluorescent metabolites by 1…
Azulene as a biphenyl mimetic in orexin/hypocretin receptor agonists
2023
Azulene is a rare ring structure in drugs, and we investigated whether it could be used as a biphenyl mimetic in known orexin receptor agonist Nag 26, which is binding to both orexin receptors OX1 and OX2 with preference towards OX2. The most potent azulene-based compound was identified as an OX1 orexin receptor agonist (pEC50 = 5.79 +/- 0.07, maximum response = 81 +/- 8% (s.e.m. of five independent experiments) of the maximum response to orexin-A in Ca2+ elevation assay). However, the azulene ring and the biphenyl scaffold are not identical in their spatial shape and electron distribution, and their derivatives may adopt different binding modes in the binding site. Peer reviewed
A New Benzopyranyl Cadenane Sesquiterpene and Other Antiplasmodial and Cytotoxic Metabolites from Cleistochlamys kirkii
2019
Phytochemical investigations of ethanol root bark and stem bark extracts of Cleistochlamys kirkii (Benth.) Oliv. (Annonaceae) yielded a new benzopyranyl cadinane-type sesquiterpene (cleistonol, 1) alongside 12 known compounds (2&ndash
The azulene scaffold from a medicinal chemist's perspective: Physicochemical and in vitro parameters relevant for drug discovery.
2022
Azulene is a bicyclic scaffold rarely applied in medicinal chemistry. Here we report physicochemical and in vitro parameters relevant for drug discovery for a series of diversely substituted azulenes. We synthesized and characterized several scaffold hopping series of analogously substituted azulenes, indoles and naphthalenes. This enabled a comparison of azulene with the more common scaffolds indole and naphthalene. Our data indicates that undesirably low photostability of azulenes is restricted to certain substitution patterns. Generally, we conclude that azulene is an underused lipophilic bicycle and should be considered as a valuable complement to the collection of medicinal chemistry s…
Acetic Acid Mediated for One-Pot Synthesis of Novel Pyrazolyl s-Triazine Derivatives for the Targeted Therapy of Triple-Negative Breast Tumor Cells (…
2022
Here, we described the synthesis of novel pyrazole-s-triazine derivatives via an easy one-pot procedure for the reaction of β-dicarbonyl compounds (ethylacetoacetate, 5,5-dimethyl-1,3-cyclohexadione or 1,3-cyclohexadionone) with N,N-dimethylformamide dimethylacetal, followed by addition of 2-hydrazinyl-4,6-disubstituted-s-triazine either in ethanol-acetic acid or neat acetic acid to afford a novel pyrazole and pyrazole-fused cycloalkanone systems. The synthetic protocol proved to be efficient, with a shorter reaction time and high chemical yield with broad substrates. The new pyrazolyl-s-triazine derivatives were tested against the following cell lines: MCF-7 (breast cancer); MDA-MB-231 (tr…
Synthesis of N‐Monosubstituted Sulfondiimines by Metal‐free Iminations of Sulfiliminium Salts
2023
Sulfondiimines are marginalized entities among nitrogencontaining organosulfur compounds, despite offering promising properties for applications in various fields including medicinal and agrochemical. Herein, we present a metal-free and rapid synthetic procedure for the synthesis of N-monosubstituted sulfondiimines that overcomes current limitations in their synthetic accessibility. Particularly, S,S-dialkyl substrates, which are commonly difficult to convert by existing methods, react well with a combination of iodine, 1,8-diazabicyclo[5.4.0]undec-7-en (DBU), and iminoiodanes (PhINR) in acetonitrile (MeCN) to furnish the corresponding sulfondiimines in yields up to 85% (25 examples). Valua…
Pharmaceuticals in processing of municipal sewage sludge studied by grab and passive sampling
2018
Abstract Concentrations of pharmaceuticals, consisting of four anti-inflammatory and one antiepileptic drug, were studied in the aqueous and solid phase of municipal sewage sludge, collected from a wastewater treatment plant (WWTP) in central Finland. The samples included untreated municipal sludge from the biological wastewater treatment, digested sludge and sludge before and after composting. First, samples were taken as grab samples to study the bioavailable part in aqueous phase but also the part in solid fraction. Later, the long-term concentrations were studied by passive sampling with styrene divinylbenzene-reverse phase sulfonated (SDB-RPS) disks. In the untreated solid sludge, the …