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Volumn 42, Issue 14, 1999, Pages 2633-2640

α-Functionalized phosphonylphosphinates: Synthesis and evaluation as transcarbamoylase inhibitors

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; ORNITHINE CARBAMOYLTRANSFERASE; PHOSPHONIC ACID DERIVATIVE; PHOSPHONYLPHOSPHINATE DERIVATIVE; UNCLASSIFIED DRUG;

EID: 0033566093     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm991008q     Document Type: Article
Times cited : (28)

References (73)
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    • An elegant method for the synthesis of benzyloxycarbonyl-protected α-aminoalkylphosphinic acids was recently published by Chen and Coward (Chen, S.; Coward, J. K. Tetrahedron Lett. 1996, 37, 4335-4338) involving three-component coupling of an alkylphosphonous acid, aldehyde, and benzyl carbamate with yields (for formaldehyde) between 50% and 67%. However, it is unclear whether this reaction can be adapted to phosphonylphosphinic acids or whether an amino acid side chain could be subsequently appended to the amine since the required electrophilic amino acid derivatives in the ornithine series are very unstable ( Feldman, P. L.; Chi, S. Bioorg. Med. Chem. Lett. 1996, 6, 111-114; Flohr, A. Unpublished results).
    • (1996) Tetrahedron Lett. , vol.37 , pp. 4335-4338
    • Chen, S.1    Coward, J.K.2
  • 26
    • 0030022891 scopus 로고    scopus 로고
    • An elegant method for the synthesis of benzyloxycarbonyl-protected α-aminoalkylphosphinic acids was recently published by Chen and Coward (Chen, S.; Coward, J. K. Tetrahedron Lett. 1996, 37, 4335-4338) involving three-component coupling of an alkylphosphonous acid, aldehyde, and benzyl carbamate with yields (for formaldehyde) between 50% and 67%. However, it is unclear whether this reaction can be adapted to phosphonylphosphinic acids or whether an amino acid side chain could be subsequently appended to the amine since the required electrophilic amino acid derivatives in the ornithine series are very unstable ( Feldman, P. L.; Chi, S. Bioorg. Med. Chem. Lett. 1996, 6, 111-114; Flohr, A. Unpublished results).
    • (1996) Bioorg. Med. Chem. Lett. , vol.6 , pp. 111-114
    • Feldman, P.L.1    Chi, S.2
  • 27
    • 0344237969 scopus 로고    scopus 로고
    • Unpublished results
    • An elegant method for the synthesis of benzyloxycarbonyl-protected α-aminoalkylphosphinic acids was recently published by Chen and Coward (Chen, S.; Coward, J. K. Tetrahedron Lett. 1996, 37, 4335-4338) involving three-component coupling of an alkylphosphonous acid, aldehyde, and benzyl carbamate with yields (for formaldehyde) between 50% and 67%. However, it is unclear whether this reaction can be adapted to phosphonylphosphinic acids or whether an amino acid side chain could be subsequently appended to the amine since the required electrophilic amino acid derivatives in the ornithine series are very unstable ( Feldman, P. L.; Chi, S. Bioorg. Med. Chem. Lett. 1996, 6, 111-114; Flohr, A. Unpublished results).
    • Flohr, A.1
  • 29
    • 0344669385 scopus 로고
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    • (1992)
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    • Tippett, S., Ed.; Specialist Periodical Reports: London
    • Hutchinson, D. W. In Organophosphorus Chemistry; Tippett, S., Ed.; Specialist Periodical Reports: London, 1970; Vol. 1, pp 134-140.
    • (1970) Organophosphorus Chemistry , vol.1 , pp. 134-140
    • Hutchinson, D.W.1
  • 32
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    • Sasse, K. In Methoden Org. Chem. (Houben Weyl); Müller, E., Ed.; Thieme: Stuttgart, 1964; Vol. XII/2, pp 5-82, 221.
    • (1964) Methoden Org. Chem. (Houben Weyl) , vol.2-12 , pp. 5-82
    • Sasse, K.1
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    • 29 but details of the assay conditions were not provided
    • 29 but details of the assay conditions were not provided.
  • 54
    • 0000975054 scopus 로고
    • a's, however, is complicated by the large number of ionizable groups in the different phosphonylphosphinate derivatives and the likelihood that these compounds exist in multiple, rapidly interconverting protonation states under physiological conditions, making detailed mechanistic conclusions difficult.
    • (1950) Monatsh. Chem. , vol.81 , pp. 202-212
    • Schwarzenbach, G.1    Zurc, J.2
  • 55
    • 0344237957 scopus 로고
    • a's, however, is complicated by the large number of ionizable groups in the different phosphonylphosphinate derivatives and the likelihood that these compounds exist in multiple, rapidly interconverting protonation states under physiological conditions, making detailed mechanistic conclusions difficult.
    • (1987) J. Chem. Soc., Dalton Trans. , pp. 87-92
    • Sanna, D.1    Micera, G.2    Buglyo, P.3    Kiss, T.4
  • 58
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    • The carbamoyl phosphate binding pockets of different transcarbamoylases are known to be highly conserved: Kraus, J. P.; Hodges, P. E.; Williamson, C. L.; Horwich, A. L.; Kalousek, F.; Williams, K. R.; Rosenberg, L. E. Nucleic Acids Res. 1985, 13, 943-952. Murata, L. B.; Schachman, H. K. Protein Sci. 1996, 5, 719-728.
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    • Murata, L.B.1    Schachman, H.K.2
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    • 43 UV difference spectroscopy suggests that carbamoyl phosphate and L-PALO induce similar changes in this enzyme (Goldsmith, J. O.; Kuo, L. C. J. Biol. Chem. 1993, 268, 18481-18484; 1991, 266, 18626-18634).
    • (1993) J. Biol. Chem. , vol.268 , pp. 18481-18484
    • Goldsmith, J.O.1    Kuo, L.C.2
  • 61
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    • 43 UV difference spectroscopy suggests that carbamoyl phosphate and L-PALO induce similar changes in this enzyme (Goldsmith, J. O.; Kuo, L. C. J. Biol. Chem. 1993, 268, 18481-18484; 1991, 266, 18626-18634).
    • (1991) J. Biol. Chem. , vol.266 , pp. 18626-18634
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* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.