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.

New Derivatives of the Multi-Stage Active Malaria Box Compound MMV030666 and Their Antiplasmodial Potencies.

MMV's Malaria Box compound MMV030666 shows multi-stage activity against various strains of and lacks resistance development. To evaluate the importance of its diarylether partial structure, diarylthioethers and diphenylamines with varying substitution patterns were prepared. A number of evident structure-activity relationships were revealed.

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 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).

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.

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.

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.

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

Some antimalarial agents in use typically bear basic side chains as ligands. Such ligands were attached to the amino substituent of a bridgehead atom of already antiprotozoal active 3-azabicyclo[3.2.

3β-Hydroxy-28-norolea-12,17-dien-11-one.

The title compound, C29H44O2, was formed by treatment of 11-oxooleanolic acid under strong alkaline conditions. The absolute structure of the chiral mol-ecules could not be determined reliably from the diffraction data, but is known from other triterpenes. The asymmetric unit consists of two mol-ecules, 1 and 2.

1,2-substituted 4-(1H)-quinolones: synthesis, antimalarial and antitrypanosomal activities in vitro.

A diverse array of 4-(1H)-quinolone derivatives bearing substituents at positions 1 and 2 were synthesized and evaluated for antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense, and cytotoxicity against L-6 cells in vitro. Furthermore, selectivity indices were also determined for both parasites. All compounds tested showed antimalarial activity at low micromolar concentrations, with varied degrees of selectivity against L-6 cells.

Antiprotozoal activity of bicyclic diamines with a N-methylpiperazinyl group at the bridgehead atom.

ω-Aminoacyl and -alkyl derivatives of 4-(4-methylpiperazin-1-yl)bicyclo[2.2.2]octan-2-amines and of 5-(4-methylpiperazin-1-yl)-2-azabicyclo[3.

New N-methylpiperazinyl derivatives of bicyclic antiprotozoal compounds.

The 4-methylpiperazinyl group was inserted as substituent at the bridgehead of bicyclic compounds or as terminal group of their aminoacyl and aminoalkyl side chains. The new compounds were tested in vitro for their activities against the multidrug-resistant K(1) strain of Plasmodium falciparum and Trypanosoma brucei rhodesiense (STIB 900). The results were compared to those of formerly prepared analogues and of drugs in use.

Dialkylaminoalkyl derivatives of bicyclic compounds with antiplasmodial activity.

Dialkylaminoalkyl derivatives of 2-azabicyclo[3.2.2]nonanes and of bicyclo[2.

1,3-Diphenyl-3,4-dihydro-benzo[b][1,6]naphthyridine.

The title compound, C(24)H(18)N(2), is the first structural example containing the 3,4-dihydro-benzo[b][1,6]naphthyridine fragment. It was synthesized from 2,4,6,8-tetra-phenyl-3,7-diaza-bicyclo-[3.3.