TY - JOUR
T1 - Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety
AU - Obata, Rika
AU - Sunazuka, Toshiaki
AU - Tian, Zhiming
AU - Tomoda, Hiroshi
AU - Harigaya, Yoshihiro
AU - Omura, Satoshi
PY - 1997/3
Y1 - 1997/3
N2 - Structure-activity relationships of the pyridine-pyrone moiety in pyripyropene A (1), a potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor of fungal origin, were studied. Several kinds of aromatic or hetero ring substituents for the pyridine moiety were synthesized using unique degradation reaction, following by γ-acylation. All the six synthesized analogs decreased the inhibitory activity with 20 to 200 times larger IC50 values than that of 1. Furthermore, the pyridine-pyrone substituent also dramatically decrease the inhibitory activity. Thus, the pyridine-pyrone moiety is important for eliciting potent ACAT inhibition.
AB - Structure-activity relationships of the pyridine-pyrone moiety in pyripyropene A (1), a potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor of fungal origin, were studied. Several kinds of aromatic or hetero ring substituents for the pyridine moiety were synthesized using unique degradation reaction, following by γ-acylation. All the six synthesized analogs decreased the inhibitory activity with 20 to 200 times larger IC50 values than that of 1. Furthermore, the pyridine-pyrone substituent also dramatically decrease the inhibitory activity. Thus, the pyridine-pyrone moiety is important for eliciting potent ACAT inhibition.
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U2 - 10.7164/antibiotics.50.229
DO - 10.7164/antibiotics.50.229
M3 - Article
C2 - 9127194
AN - SCOPUS:0030895419
SN - 0021-8820
VL - 50
SP - 229
EP - 236
JO - Journal of Antibiotics
JF - Journal of Antibiotics
IS - 3
ER -