Mathias Osswald

3-substituted 6-butyl-1,2-dihydropyridin-2-ones: A new series of potent nonpeptide angiotensin II receptor antagonists

Abstract The syntheses and biological activities of a series of novel 3-substituted 6-butyl-1,2-dihydro-pyridin-2-ones are presented. A number of these compounds are shown to be potent antagonists of angiotensin II with in vitro potencies in the nanomolar or even subnanomolar range. They also have proven their suitability as effective inhibitors of angiotensin II pressor response in vivo.

On the regiochemistry of the alkylation of tert-butyl N-[6-butyl-1,2-dihydro-2-oxo-3-pyridylmethyl]carbamate: Precursor of a series of potent angiotensin II receptor antagonists

Abstract The key intermediate 5 of a large number of potent AT 1 selective angiotensin II antagonists e.g. the potent cyclopropylmethyl derivative 1 (EMD 69943) was synthesized by regioselective alkylation of carbamate 3 with the well-known 4′-(bromomethyl)biphenyl-2-carbonitrile ( 4 ) and n-butyllithium as the preferred base.

URACIL-BASED ANGIOTENSIN II RECEPTOR ANTAGONISTS

1,2,3,4-Tetrahydro-2,4-pyrimidinedione (uracil) is a valuable nucleus for the construction of potent antagonists of the AT1 angiotensin II receptor. Various synthetic routes were applied in order to introduce a wide range of different groups at the N3-nitrogen and to obtain condensed uracil derivatives as well. 121 with a N,N-dimethylacetamide residue at N3 was the most potent compound with an IC50 of 0.65 nM.