Science Links Japan | Studies on the Metabolic Fate of Amrubicin Hydrochloride(SM-5887), a Novel Antitumor Agent (9)-In Vivo Chiral Conversion of SM-5887 and Stereoselectivity of Reduction of the Carbonyl Group at the C-13 Position.

Studies on the Metabolic Fate of Amrubicin Hydrochloride(SM-5887), a Novel Antitumor Agent (9)-In Vivo Chiral Conversion of SM-5887 and Stereoselectivity of Reduction of the Carbonyl Group at the C-13 Position.

Accession number;99A0241105

Title;Studies on the Metabolic Fate of Amrubicin Hydrochloride(SM-5887), a Novel Antitumor Agent (9)-In Vivo Chiral Conversion of SM-5887 and Stereoselectivity of Reduction of the Carbonyl Group at the C-13 Position.

Author; NAKAI SHUNJI (Sumitomo Chemical Co., Ltd.) ITO MASAKI (Sumitomo Chemical Co., Ltd.) KANAMARU HIROSHI (Sumitomo Chemical Co., Ltd.) NAKATSUKA IWAO (Sumitomo Chemical Co., Ltd.)

Journal Title;Japanese Pharmacology & Therapeutics

Journal Code:Z0947A

ISSN:0386-3603

VOL.27;NO.Suppl.1;PAGE.S.557-S.568(1999)

Figure&Table&Reference;FIG.8, TBL.3, REF.6

Pub. Country;Japan

Language;Japanese

Abstract;In vivo chiral conversions at the C-7 and C-9 positions of the anthracycline moiety of amrubicin hydrochloride(SM-5887) were investigated. Furthermore, the stereoselectivities of the in vitro and in vivo reduction of SM-5887 to amrubicinol(SM-5887-13-OH, the major bioactive metabolite) at the C-13 position of the side-chain were studied. 1) By analyzing the SM-5887 fraction of serum obtained from rats receiving intravenous administration of SM-5887, only the stereoisomer possessing the same(7S,9S) configuiration as SM-5887 was observed, and other stereoisomers of SM-5887((7R,9S),(7S,9R) and (7R,9R)) were not distinctly observed(less than 2% of SM-5887 content) after administration of SM-5887. This result suggests that little chiral conversion at the C-7 or C-9 positions of SM-5887 occurred in vivo, if any. 2) More than 90% of SM-5887-13-OH in plasma, urine and tissues of rats and dogs receiving intravenous administration of SM-5887 had the 13S configuration. Besides, in vitro metabolic reaction using liver cytosols of rat, dog and human revealed that more than 97% of SM-5887-13-OH had the 13S configuration, which further confirmed the high stereoselectivity of the reduction of the carbonyl group at the C-13 position. (author abst.)

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