Nonpeptidic inhibitors of human leukocyte elastase. 5. Design, synthesis, and x-ray crystallography of a series of orally active 5-aminopyrimidin-6-one-containing trifluoromethyl ketones was written by Veale, Chris A.;Bernstein, Peter R.;Bryant, Craig;Ceccarelli, Christopher;Damewood, James R. Jr.;Earley, Roger;Feeney, Scott W.;Gomes, Bruce;Kosmider, Ben J.. And the article was included in Journal of Medicinal Chemistry in 1995.Name: 5-Aminopyrimidin-4(3H)-one This article mentions the following:
The effects of changes in substitution in a series of 5-amino-2-pyrimidin-6-ones on both in vitro elastase-inhibitory activity and oral activity in an acute hemorrhagic assay were explored. These compounds contained either a trifluoromethyl ketone or a boronic acid moiety to bind covalently to the serine-195 OH group of human leukocyte elastase (HLE). Boronic acid-containing inhibitors were more potent than the corresponding trifluoromethyl ketones in vitro but were less active upon oral administration. One compound (I; R1 = H; Ar = 4-fluorophenyl; R2 = trifluoromethyl ketone) offered the best combination of oral potency, duration of action, and enzyme selectivity and, as such, was selected for further biol. testing. X-ray crystallog. of a cocrystd. complex of another compound (I; R1 = CH3SO2; Ar = 4-aminophenyl; R2 = trifluoromethyl ketone) and porcine pancreatic elastase demonstrated that the inhibitor is bound to the enzyme in a manner similar to that found previously for a closely related series of pyridone-containing inhibitors of HLE. In the experiment, the researchers used many compounds, for example, 5-Aminopyrimidin-4(3H)-one (cas: 69785-94-0Name: 5-Aminopyrimidin-4(3H)-one).
5-Aminopyrimidin-4(3H)-one (cas: 69785-94-0) belongs to pyrimidine derivatives. Pyrimidine also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.Name: 5-Aminopyrimidin-4(3H)-one
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia