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Volumn 46, Issue 48, 2007, Pages 9312-9315

The 1,2,3-triazole ring as a peptido- and olefinomimetic element: Discovery of click yanilloids and cannabinoids

Author keywords

Cannabinoids; Cycloaddition; Drug design; Triazoles; Vanilloids

Indexed keywords

CANNABINOIDS; DRUG DESIGN; TRIAZOLES; VANILLOIDS;

EID: 37349065872     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200703590     Document Type: Article
Times cited : (62)

References (29)
  • 1
    • 34547272503 scopus 로고    scopus 로고
    • For recent reviews, see: a
    • For recent reviews, see: a) J. E. Moses, A. D. Moorhouse, Chem. Soc. Rev. 2007, 36, 1249-1262;
    • (2007) Chem. Soc. Rev , vol.36 , pp. 1249-1262
    • Moses, J.E.1    Moorhouse, A.D.2
  • 4
    • 35348874833 scopus 로고    scopus 로고
    • d) J. F. Lutz, Angew. Chem. 2007, 119, 1036-1043;
    • (2007) Angew. Chem , vol.119 , pp. 1036-1043
    • Lutz, J.F.1
  • 5
    • 34247237682 scopus 로고    scopus 로고
    • Angew. Chem. Int. Ed. 2007, 46, 1018-1025;
    • (2007) Chem. Int. Ed , vol.46 , pp. 1018-1025
    • Angew1
  • 7
    • 0348109450 scopus 로고    scopus 로고
    • In 1,4-substituted triazoles, the carbon atom at the 4-position and the C-H bond can act as an electrophilic site and a hydrogen-bond donor, respectively, whereas the pyridine-type lone pair of electrons on the nitrogen atom at the 3-position serves as a hydrogen-bond-acceptor element. The overall dipolar moment of the triazole system is larger than that of the amide bond, and its hydrogen-bond donor and acceptor properties are therefore more marked that those of an amide bond. The larger dipole moment may compensate for the increased distance between the substituents relative to the distance between substituents on a Z amide bond 3.9 versus 5.0 Å, 1d] Although this geometrical mismatch does not exist in 1,5-substituted derivatives, the degree to which they mimic an E amide bond is undermined somewhat by the poor electrophilicity of the pyrrole-like nitrogen atom relative to that of a carbonyl carbon atom. For a discussion, see, H. C. Kolb, K. B. Sharp
    • [1d] Although this geometrical mismatch does not exist in 1,5-substituted derivatives, the degree to which they mimic an E amide bond is undermined somewhat by the poor electrophilicity of the pyrrole-like nitrogen atom relative to that of a carbonyl carbon atom. For a discussion, see : H. C. Kolb, K. B. Sharpless, Drug Discovery Today 2003, 24, 1128-1137. (Chemical Equation Presented)
  • 10
    • 34447515534 scopus 로고    scopus 로고
    • for a related study involving a cellular endpoint induction of apoptosis, see
    • for a related study involving a cellular endpoint (induction of apoptosis), see: S. Kim, M. Cho, T. Lee, S. Lee, H.-Y. Min, S. Kook, Bioorg. Med. Chem. Lett. 2007, 17, 4584-4587.
    • (2007) Bioorg. Med. Chem. Lett , vol.17 , pp. 4584-4587
    • Kim, S.1    Cho, M.2    Lee, T.3    Lee, S.4    Min, H.-Y.5    Kook, S.6
  • 11
    • 37349096869 scopus 로고    scopus 로고
    • For a recent review on the structure-activity relationships of capsaicinoids, see:, Eds, E. Fattorusso, O. Taglialatela-Scafati, Wiley-VCH, Weinheim
    • For a recent review on the structure-activity relationships of capsaicinoids, see: G. Appendino in Modern Alkaloids: Structure, Isolation, Synthesis and Biology (Eds.: E. Fattorusso, O. Taglialatela-Scafati), Wiley-VCH, Weinheim, 2007, pp. 75-112.
    • (2007) Modern Alkaloids: Structure, Isolation, Synthesis and Biology , pp. 75-112
    • Appendino, G.1
  • 17
    • 0029619205 scopus 로고    scopus 로고
    • [5]
    • [5]
  • 20
    • 2442642767 scopus 로고    scopus 로고
    • TRP channels are sensitive to metal inhibition, and the dye ruthenium red is a general inhibitor of this type of channel (A. Szallasi, G. Appendino, J. Med. Chem. 2004, 47, 2717-2723).
    • TRP channels are sensitive to metal inhibition, and the dye ruthenium red is a general inhibitor of this type of channel (A. Szallasi, G. Appendino, J. Med. Chem. 2004, 47, 2717-2723).
  • 21
    • 33846551684 scopus 로고    scopus 로고
    • In previous studies involving metathesis reactions, we observed that capsaicinoids strongly retain metal impurities.[19] The final products were therefore purified carefully by crystallization and preparative HPLC, and examined for inorganic contaminants by atomic spectroscopy. A copper or ruthenium content of less than 3 ppm was found. Furthermore. 4a showed the same activity against the three endpoints investigated (TRPV1, CB1, and CB2) regardless of whether it had been obtained under Cu I or RuII catalysis. Despite the presence of the same potential copper impurity, iodine-induced reversal of activity was observed, as expected, for 4b. Taken together, these observations make it unlikely that transition-metal contaminants have affected the bioactivity data. For recent examples of the mediation of the activity of proteins within the endocannabinoid system by spurious metal impurities, see: S. Vandevoorde, K. O. Jonsson, G. Labar
    • II catalysis. Despite the presence of the same potential copper impurity, iodine-induced reversal of activity was observed, as expected, for 4b. Taken together, these observations make it unlikely that transition-metal contaminants have affected the bioactivity data. For recent examples of the mediation of the activity of proteins within the endocannabinoid system by spurious metal impurities, see: S. Vandevoorde, K. O. Jonsson, G. Labar, E. Persson, D. M. Lambert, C. J. Fowler, Br. J. Pharmacol. 2007, 150, 186-191;
  • 23
    • 0033584439 scopus 로고    scopus 로고
    • 1: D. Melck, T. Bisogno, L. De Petrocellis, H. Chuang, D. Julius, M. Bifulco, V. Di Marzo, Biochem. Biophys. Res. Commun, 1999, 262, 275-284.
    • 1: D. Melck, T. Bisogno, L. De Petrocellis, H. Chuang, D. Julius, M. Bifulco, V. Di Marzo, Biochem. Biophys. Res. Commun, 1999, 262, 275-284.
  • 29
    • 33846638747 scopus 로고    scopus 로고
    • A similar observation was made for a series of phosphatidylcholine- derived bolaamphiphiles, whereby the presence of a 1,4-triazole moiety in the lipid linker was detrimental to vesicle formation: E. J. O'Neil, K. M. DiVittorio, B. D. Smith, Org. Lett. 2007, 9, 199-202.
    • A similar observation was made for a series of phosphatidylcholine- derived bolaamphiphiles, whereby the presence of a 1,4-triazole moiety in the lipid linker was detrimental to vesicle formation: E. J. O'Neil, K. M. DiVittorio, B. D. Smith, Org. Lett. 2007, 9, 199-202.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.