Document Detail

Structure determination of metabolites isolated from urine and bile after administration of AY4166, a novel D-phenylalanine-derivative hypoglycemic agent.
MedLine Citation:
PMID:  8931947     Owner:  NLM     Status:  MEDLINE    
Molecular structures of 10 metabolites, which were isolated from urine (M1-M8) or bile (M9 and M10) after administration of AY4166 (N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine), a novel amino acid derivative with hypoglycemic activity, have been elucidated by mass spectrometry and nuclear magnetic resonance. Four of these (M1, M2, M3 and M8) were determined to be hydroxyl derivatives of AY4166, two (M9 and M10) were carboxylate derivatives via oxidization of M2 and M3, three (M4, M5 and M6) were glucronic acid conjugates and the other (M7) was a dehydro derivative. The estimated structures for M1, M2, M3, M7, M8, M9 and M10 were confirmed by the coincidence of the retention time of HPLC, MS and 1H NMR spectra between the isolated metabolites and authentic synthesized substances. For three glucronic acid conjugates, M4, M5 and M6, structural confirmation was performed by a selective enzymatic digestion with beta-glucronidase. M1 and M2/3 were about 5-6 and 3 times less potent than AY4166, respectively, and M7 was almost as potent as AY4166.
H Takesada; K Matsuda; R Ohtake; R Mihara; I Ono; K Tanaka; M Naito; M Yatagai; E Suzuki
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  4     ISSN:  0968-0896     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1997-03-03     Completed Date:  1997-03-03     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1771-81     Citation Subset:  IM    
Central Research Laboratories, Ajinomoto Co., Inc, Kawasaki, Japan.
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MeSH Terms
Bile / chemistry*
Cyclohexanes / administration & dosage,  pharmacokinetics*,  urine
Glucuronidase / metabolism
Hypoglycemic Agents / administration & dosage,  pharmacokinetics*
Magnetic Resonance Spectroscopy
Models, Molecular
Phenylalanine / administration & dosage,  analogs & derivatives*,  pharmacokinetics,  urine
Reg. No./Substance:
0/Cyclohexanes; 0/Hypoglycemic Agents; 105816-04-4/nateglinide; 63-91-2/Phenylalanine; EC
Erratum In:
Bioorg Med Chem 1997 Mar;5(3):637

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