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 microM 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.
Singh
S B
SB
Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. sheo_singh@merck.com
Graham
P L
PL
Reamer
R A
RA
Cordingley
M G
MG
D000086042:3C Viral Proteases; D003546:Cysteine Endopeptidases; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
C447630:2-Methoxystypandrone; D009285:Naphthoquinones; D011480:Protease Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases