Solution-phase parallel synthesis of 5-carboxamido 1-benzyl-3-(3-dimethylaminopropyloxy)-1H-pyrazoles as activators of soluble guanylate cyclase with improved oral bioavailability

Overcoming co‐product inhibition in the nicotinamide independent asymmetric bioreduction of activated CC‐bonds using flavin‐dependent ene‐reductases

“…A search for a suitable phenol‐adsorbing polymeric material revealed macroporous polystyrene (MP‐)carbonate as a suitable candidate (Lyon and Kercher, ; Selwood et al, ). The latter possesses positively charged triethylammonium‐groups linked to an aromatic styrene moiety, which enables ionic binding of the phenolate anion supported by π–π stacking of both aromatic systems (Fig.…”

Copper (II)-Mediated Arylation with Aryl Boronic Acids for the N-Derivatization of Pyrazole Libraries

“…Ideally, reactions should be carried out in a parallel fashion with simple workups utilizing filtration rather than liquid−liquid extractions . In connection with our studies directed toward the discovery of activators of the soluble guanylate cyclase (sGC) enzyme, , we needed to explore N -aryl substitution of a series of pyrazole derivatives.…”

“…Library Design. Our previous investigations into the evaluation of indazole and pyrazole compounds as sGC activators indicated a general lipophilicity requirement for inhibition of platelet aggregation. , To select the compounds for synthesis, a virtual product library was generated; log P values were calculated for the virtual library, eliminating potential products with clog P > 3.0 and > 5.0. Products with molecular weight >500 were eliminated, in line with Lipinski's rules for drug-like substances .…”

Antimalarial Aminothiazoles and Aminopyridines From Phenotypic Whole-Cell Screening Of A SoftFocus ® Library

“…These scaffolds have not previously been associated with antimalarial activity. However, pyrazole amides and ureas have been reported as modulators of cell signalling, either as soluble guanylate cyclase activators [27] or as inhibitors of various kinases involved in signal transduction [28]. Since the original Bio-Focus library was created based on target focus design, kinase inhibition was not surprising.…”