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

A lipophilicity constrained library of 5-carboxamido 1-benzyl-3-(3-dimethylaminopropyloxy)-1H-pyrazoles was prepared by solution-phase parallel synthesis with removal of acidic by-products using the strongly basic MP-carbonate resin. Compounds show both activation of soluble guanylate cyclase and inhibition of platelet aggregation. Compound 12 also shows 22% oral bioavailability in rats.