TAN-931, a novel nonsteroidal aromatase inhibitor produced by Penicillium funiculosum No. 8974. II. Structure elucidation, chemical modification and biological activity.
The structure of TAN-931, a novel nonsteroidal aromatase inhibitor, was determined by chemical reactions and spectral analyses including 2D NMR experiments to be 4-(2,6-dihydroxybenzoyl)-3-formyl-5-hydroxybenzoic acid. Several derivatives of TAN-931 were prepared, and it was found that the 3-formyl and 2'- and/or 6'-hydroxyl groups play an important role in its inhibitory activity. Among the compounds synthesized, 4-(2,6-dihydroxybenzoyl)-3-formyl-5-methoxy-N,N-dimethyl-benzamide was found to be more effective than TAN-931 when administered orally.
Hida
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Microbiology Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Ishii
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Kanamaru
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Muroi
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D000284:Administration, Oral; D000818:Animals; D047072:Aromatase Inhibitors; D005260:Female; D006801:Humans; D062385:Hydroxybenzoates / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects*; D010407:Penicillium / Q000378:metabolism; D010920:Placenta / Q000187:drug effects*; D051381:Rats; D013055:Spectrophotometry, Infrared; D014599:Uterus / Q000187:drug effects*
C069914:4-(2,6-dihydroxybenzoyl)-3-formyl-5-hydroxybenzoic acid; D047072:Aromatase Inhibitors; D062385:Hydroxybenzoates