Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety

Rika Obata, Toshiaki Sunazuka, Zhiming Tian, Hiroshi Tomoda, Yoshihiro Harigaya, Satoshi Omura

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)229-236
Number of pages8
JournalJournal of Antibiotics
Volume50
Issue number3
Publication statusPublished - 1997 Mar
Externally publishedYes

Fingerprint

Pyrones
Structure-Activity Relationship
Sterol O-Acyltransferase
Anticholesteremic Agents
Acylation
Inhibitory Concentration 50
pyridine

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Obata, R., Sunazuka, T., Tian, Z., Tomoda, H., Harigaya, Y., & Omura, S. (1997). Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety. Journal of Antibiotics, 50(3), 229-236.

Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety. / Obata, Rika; Sunazuka, Toshiaki; Tian, Zhiming; Tomoda, Hiroshi; Harigaya, Yoshihiro; Omura, Satoshi.

In: Journal of Antibiotics, Vol. 50, No. 3, 03.1997, p. 229-236.

Research output: Contribution to journalArticle

Obata, R, Sunazuka, T, Tian, Z, Tomoda, H, Harigaya, Y & Omura, S 1997, 'Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety', Journal of Antibiotics, vol. 50, no. 3, pp. 229-236.
Obata, Rika ; Sunazuka, Toshiaki ; Tian, Zhiming ; Tomoda, Hiroshi ; Harigaya, Yoshihiro ; Omura, Satoshi. / Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety. In: Journal of Antibiotics. 1997 ; Vol. 50, No. 3. pp. 229-236.
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