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Steroidomimetic Aminomethyl Spiroacetals as Novel Inhibitors of the Enzyme Δ8,7‐ S terol Isomerase in Cholesterol Biosynthesis
Author(s) -
Krojer Melanie,
Müller Christoph,
Bracher Franz
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201300296
Subject(s) - hydroxymethyl , chemistry , isomerase , enzyme , ketone , stereochemistry , bicyclic molecule , moiety , biosynthesis , sterol , biochemistry , cholesterol , organic chemistry
Grundmann's ketone is converted to a spiroacetal containing a 5‐hydroxymethyl‐5‐nitro‐1,3‐dioxane moiety whose hydroxymethyl group can be esterified or directly substituted with primary and secondary amines. Among the resulting aminomethyl spiroacetals, several ones bearing diamino residues were found to be inhibitors of the enzyme Δ8,7‐isomerase in cholesterol biosynthesis. The complex bicyclic building block derived from Grundmann's ketone could be replaced by a properly substituted tetraline scaffold, without noteworthy loss in activity. This opens the opportunity to perform further structural modifications for the design of new steroidomimetic inhibitors of human Δ8,7‐isomerase.