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PDBsum entry 4tww
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Hydrolase/hydrolase inhibitor
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PDB id
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4tww
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References listed in PDB file
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Key reference
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Title
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Fused-Ring structure of decahydroisoquinolin as a novel scaffold for sars 3cl protease inhibitors.
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Authors
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Y.Shimamoto,
Y.Hattori,
K.Kobayashi,
K.Teruya,
A.Sanjoh,
A.Nakagawa,
E.Yamashita,
K.Akaji.
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Ref.
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Bioorg Med Chem Lett, 2015,
23,
876-890.
[DOI no: ]
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PubMed id
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Abstract
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The design and evaluation of a novel decahydroisoquinolin scaffold as an
inhibitor for severe acute respiratory syndrome (SARS) chymotrypsin-like
protease (3CL(pro)) are described. Focusing on hydrophobic interactions at the
S2 site, the decahydroisoquinolin scaffold was designed by connecting the P2
site cyclohexyl group of the substrate-based inhibitor to the main-chain at the
α-nitrogen atom of the P2 position via a methylene linker. Starting from a
cyclohexene enantiomer obtained by salt resolution, trans-decahydroisoquinolin
derivatives were synthesized. All decahydroisoquinolin inhibitors synthesized
showed moderate but clear inhibitory activities for SARS 3CL(pro), which
confirmed the fused ring structure of the decahydroisoquinolin functions as a
novel scaffold for SARS 3CL(pro) inhibitor. X-ray crystallographic analyses of
the SARS 3CL(pro) in a complex with the decahydroisoquinolin inhibitor revealed
the expected interactions at the S1 and S2 sites, as well as additional
interactions at the N-substituent of the inhibitor.
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