Formation of 5-Aminomethyl-2,3-dihydropyridine-4(1)-ones from 4-Amino-tetrahydropyridinylidene Salts.

Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in an alkaline medium. Their conversion to 5-substituted β-hydroxyketones in a one-step reaction succeeded only with an aliphatic aldehyde. Instead, aromatic aldehydes gave 5-substituted β-aminoketones or a single δ-diketone.

Structure-Activity Relationships and Antiplasmodial Potencies of Novel 3,4-Disubstituted 1,2,5-Oxadiazoles.

The 4-substituted 3-amino-1,2,5-oxadiazole from the Malaria Box Project of the Medicines for Malaria Venture foundation shows very promising selectivity and in vitro activity against . Within the first series of new compounds, various 3-acylamino analogs were prepared. This paper now focuses on the investigation of the importance of the aromatic substituent in ring position 4.

Synthesis and Antiprotozoal Activity of Azabicyclo-Nonane Pyrimidine Hybrids.

2,4-Diaminopyrimidines and (dialkylamino)azabicyclo-nonanes possess activity against protozoan parasites. A series of fused hybrids were synthesized and tested in vitro against pathogens of malaria tropica and sleeping sickness. The activities and selectivities of compounds strongly depended on the substitution pattern of both ring systems as well as on the position of the nitrogen atom in the bicycles.

Antiprotozoal Activity of Azabicyclo-Nonanes Linked to Tetrazole or Sulfonamide Cores.

-(Aminoalkyl)azabicyclo[3.2.2]nonanes possess antiplasmodial and antitrypanosomal activity.

Synthesis and Structure-Activity Relationships of New 2-Phenoxybenzamides with Antiplasmodial Activity.

The 2-phenoxybenzamide from the Medicines for Malaria Venture Malaria Box Project has shown promising multi-stage activity against different strains of . It was successfully synthesized via a retrosynthetic approach. Subsequently, twenty-one new derivatives were prepared and tested for their in vitro activity against blood stages of the NF54 strain of .

8-Amino-6-Methoxyquinoline-Tetrazole Hybrids: Impact of Linkers on Antiplasmodial Activity.

A new series of compounds was prepared from 6-methoxyquinolin-8-amine or its -(2-aminoethyl) analogue via Ugi-azide reaction. Their linkers between the quinoline and the -butyltetrazole moieties differ in chain length, basicity and substitution. Compounds were tested for their antiplasmodial activity against NF54 as well as their cytotoxicity against L-6-cells.

New Acyl Derivatives of 3-Aminofurazanes and Their Antiplasmodial Activities.

An -acylated furazan-3-amine of a Medicines for Malaria Venture (MMV) project has shown activity against different strains of . Seventeen new derivatives were prepared and tested in vitro for their activities against blood stages of two strains of . Several structure-activity relationships were revealed.

Preparation of new 1,3-dibenzyl tetrahydropyridinylidene ammonium salts and their antimicrobial and anticellular activities.

New 1,3 dibenzyl -tetrahydropyridinylidene ammonium salts have been prepared from unsubstituted or N-benzylated tetrahydropyridinylidene ammonium salts. The antiplasmodial and antitrypanosomal activities as well as their cytotoxic effects were determined using microplate assays. In addition, their activities against two gram positive and two gram negative bacteria strains and a yeast strain were examined.

Synthesis and characterization of zinc di(-2,2-dimethylpentan-3-yl dithiocarbonates) bearing pyridine or tetramethylethylenediamine coligands and investigation of their thermal conversion mechanisms towards nanocrystalline zinc sulfide.

Metal xanthates are versatile single source precursors for the preparation of various metal sulfides. In this study, we present the synthesis of the two novel zinc xanthate complexes bis(O-2,2-dimethylpentan-3-yl-dithiocarbonato)(N,N,N',N'-tetramethylethylenediamine)zinc(ii) and bis(O-2,2-dimethylpentan-3-yl-dithiocarbonato)(pyridine)zinc(ii). A thorough investigation of these compounds revealed distinct differences in their structural and thermal properties.

Palladium-catalysed synthesis of arylnaphthoquinones as antiprotozoal and antimycobacterial agents.

Malaria and tuberculosis are still among the leading causes of death in low-income countries. The 1,4-naphthoquinone (NQ) scaffold can be found in a variety of anti-infective agents. Herein, we report an optimised, high yield process for the preparation of various 2-arylnaphthoquinones by a palladium-catalysed Suzuki reaction.

Synthesis and structure-activity relationships for new 6-fluoroquinoline derivatives with antiplasmodial activity.

The substitution of 6-fluoroquinolines was modified in ring positions 2 and 4. The new compounds were tested in vitro for their activities against a sensitive and a multidrug resistant strain of Plasmodium falciparum. Some physicochemical parametres were calculated (log P, log D, ligand efficiency) or determined experimentally (permeability).

Synthesis of Jacaranone-Derived Nitrogenous Cyclohexadienones and Their Antiproliferative and Antiprotozoal Activities.

The cytotoxic and antiprotozoal activities of the phytoquinoide, jacaranone, and related compounds have been an ongoing topic in recent drug discovery. Starting from the natural product-derived cyclohexadienone scaffold, a series of nitrogen-containing derivatives were synthesized and subsequently evaluated for their antiproliferative and antiprotozoal activity. Anticancer potency was analyzed using different types of cancer cell lines: MDA-MB-231 breast cancer, CCRF-CEM leukemia, HCT-116 colon cancer, U251 glioblastoma, and, in addition, non-tumorigenic MRC-5 lung fibroblasts.

Antiprotozoal Activities of Tetrazole-quinolines with Aminopiperidine Linker.

Background: Human African Trypanosomiasis (HAT, sleeping sickness) and Malaria both are insect vectored tropical diseases. Only a couple of drugs is able to cure HAT, but all of them are toxic, prone to resistance and require parenteral administration. Malaria is responsible for high morbidity and mortality in humans.

Synthesis of new 1-benzyl tetrahydropyridinylidene ammonium salts and their antimicrobial and anticellular activities.

A series of N-benzyl tetrahydropiperidinylidene pyrrolidinium salts have been synthesized and investigated for their antiplasmodial and antitrypanosomal activities as well as for their cytotoxic effects. The antibacterial, antimycobacterial and anticancer potencies of selected compounds were examined, too. Physicochemical parameters were calculated and structure-activity-relationships are discussed.

New derivatives of quinoline-4-carboxylic acid with antiplasmodial activity.

New analogues of the recently published compound DDD107498 were prepared. Their activities were examined in vitro against the chloroquine-sensitive NF54 strain. The most active were also tested against the multiresistant K strain of Plasmodium falciparum.

New derivatives of 7-chloroquinolin-4-amine with antiprotozoal activity.

Novel ω-aminoacyl and -alkyl derivatives of 7-chloroquinolin-4-amine were prepared and their structures confirmed by NMR spectroscopy. Their antiprotozoal activities were examined in vitro against the sensitive NF54 strain as well as against the multiresistant K strain of Plasmodium falciparum and against Trypanosoma brucei rhodesiense (STIB 900). The results were compared with the activities of clinically used drugs.

From secondary alcohols to tertiary fluoro substituents: A simple route to hydroxymethyl branched sugars with a fluorine substituent at the branching point.

From a secondary hydroxyl group, by the simple sequence of oxidation, Wittig reaction of the obtained ulose with methoxymethylene triphenyl phosphorane, exposure of the resulting exocyclic enol ether to Selectfluor and subsequent reduction of the α-fluoro aldehyde thus obtained, tertiary fluoro substituents can be introduced into carbohydrate and carbohydrate-related scaffolds at a branching point now bearing a new hydroxymethyl group.

A trifunctional linker suitable for conducting three orthogonal click chemistries in one pot.

The feasibility of a one pot approach for conducting mutually orthogonal thiol-Michael addition, copper catalyzed azide-alkyne and inverse electron demand Diels-Alder click chemistry on a tri-functional substrate was demonstrated.

The antiprotozoal potencies of newly prepared 3-azabicyclo[3.2.2]nonanes.

3-Azabicyclo[3.2.2]nonanes are already reported as antiprotozoal agents.

Antiprotozoal activity of bicycles featuring a dimethylamino group at their bridgehead.

Several dimethylamino-derivatives of the new compound-class 3-azabicyclo[3.2.2]nonanes were prepared.

5-Fluoro derivatives of 4-epi-isofagomine as D-galactosidase inhibitors and potential pharmacological chaperones for GM1-gangliosidosis as well as Fabry's disease.

Electrophilic fluorination of an exocyclic methoxymethylene enol ether derived from N-tert-butyloxycarbonyl-1,5-dideoxy-1,5-imino-3,4-O-isopropylidene-D-erythro-pent-2-ulose (11) provided the 5-fluoro derivative of the powerful β-galactosidase inhibitor 4-epi-isofagomine (8). This structural alteration, in combination with N-alkylation, led to considerably improved α-galactosidase selectivity. New compounds may serve as leads en route to new pharmacological chaperones for Fabry's disease.

Synthesis of new 4-phenylpyrimidine-2(1H)-thiones and their potency to inhibit COX-1 and COX-2.

Several new 4-phenylpyrimidine-2(1H)-thiones have been prepared and investigated for their potencies to inhibit COX-1 and COX-2 enzymes, and COX-2 expression in THP-1 cells. Structure-activity-relationships and physicochemical parameters are discussed. Pharmacophore screening and docking studies were carried out for the most active compound.

Synthesis of 3-azabicyclo[3.2.2]nonanes and their antiprotozoal activities.

Several bicyclic compounds, 3-azabicyclo[3.2.2]nonanes, have been prepared.

Covalent adduct formation between the plasmalogen-derived modification product 2-chlorohexadecanal and phloretin.

Hypochlorous acid added as reagent or generated by the myeloperoxidase (MPO)-H2O2-Cl(-) system oxidatively modifies brain ether-phospholipids (plasmalogens). This reaction generates a sn2-acyl-lysophospholipid and chlorinated fatty aldehydes. 2-Chlorohexadecanal (2-ClHDA), a prototypic member of chlorinated long-chain fatty aldehydes, has potent neurotoxic potential by inflicting blood-brain barrier (BBB) damage.