Discovery, total synthesis, HRV 3C-protease inhibitory activity, and structure–activity relationships of 2-methoxystypandrone and its analogues

2-Methoxystypandrone, a naphthoquinone, was isolated from a Chinese herb Polygonum cuspidatum by bioassay guided fractionation using HRV 3C-protease assay. It showed an IC 50 value of 4.6 μM and is moderately selective. A new 10-step, total synthesis of 2-methoxystypandrone was accomplished in 45% o...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2001-12, Vol.11 (24), p.3143-3146
Hauptverfasser:	Singh, Sheo B, Graham, Pia L, Reamer, Robert A, Cordingley, Michael G
Format:	Artikel
Sprache:	eng
Schlagworte:	3C Viral Proteases Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Cysteine Endopeptidases Medical sciences Naphthoquinones - chemical synthesis Naphthoquinones - chemistry Naphthoquinones - isolation & purification Pharmacology. Drug treatments Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Structure-Activity Relationship Viral Proteins - antagonists & inhibitors
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container_title	Bioorganic & medicinal chemistry letters
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creator	Singh, Sheo B Graham, Pia L Reamer, Robert A Cordingley, Michael G
description	2-Methoxystypandrone, a naphthoquinone, was isolated from a Chinese herb Polygonum cuspidatum by bioassay guided fractionation using HRV 3C-protease assay. It showed an IC 50 value of 4.6 μM and is moderately selective. A new 10-step, total synthesis of 2-methoxystypandrone was accomplished in 45% overall yield using a Diels–Alder approach. Several analogues of this compound were prepared. Isolation, synthesis and HRV 3C-protease structure–activity relationships of these compounds have been described. Discovery, a new total synthesis employing Diels–Alder method, HRV 3C-protease inhibitory activity, and SAR of methoxystypandrone has been described.
doi_str_mv	10.1016/S0960-894X(01)00648-5
format	Article
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subjects	3C Viral Proteases Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Biological and medical sciences Cysteine Endopeptidases Medical sciences Naphthoquinones - chemical synthesis Naphthoquinones - chemistry Naphthoquinones - isolation & purification Pharmacology. Drug treatments Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Structure-Activity Relationship Viral Proteins - antagonists & inhibitors
title	Discovery, total synthesis, HRV 3C-protease inhibitory activity, and structure–activity relationships of 2-methoxystypandrone and its analogues
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