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Synthesis of Seco ‐Analogues of the DHCR24 Inhibitor SH‐42
Author(s) -
Heerdegen Desirée,
Reuter Doreen,
Kornmayer Moritz M.,
Kriegler Kathari.,
Müller Christoph,
Mayer Peter,
Bracher Franz
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202001080
Subject(s) - chemistry , stereochemistry , linker , ring (chemistry) , enzyme , aryl , alkyl , biochemistry , organic chemistry , computer science , operating system
In a project aimed at the further development of the potent steroidal anti‐inflammatory Δ 24 ‐dehydrocholesterol reductase (DHCR24) inhibitor SH‐42 we worked out routes to ring B s eco ‐steroidal analogues. The required building blocks, bearing rings C and D of the parent steroidal structure, were synthesised starting from ergocalciferol. The novel seco ‐analogues carry aromatic residues as ring A equivalents at C‐4 position with variation of the linker length resulting in 4‐aryl‐, 4‐benzyl‐ and 4‐(arylethyl)perhydroindanes. As saturated analogues of the latter 4‐(cyclohexylethyl)perhydroindanes were prepared. Moreover, aromatic and aliphatic residues were attached to C‐5 position of the perhydroindane scaffold. Unfortunately, none of these structurally diverse seco ‐analogues of SH‐42 showed noteworthy inhibition of target enzyme DHCR24, indicating the relevance of the intact steroidal structure for the development of potent inhibitors of this enzyme.