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ChemMedChem
Volumn 4, Issue 1, 2009, Pages 49-51
Assessing the bioisosterism of the trifluoromethyl group with a protease probe
Author keywords

Barbiturates; Bioisosterism; Isopropyl group; Matrix metalloproteases; Trifluoromethyl group
Indexed keywords

BARBITURIC ACID DERIVATIVE; METHANE; PROTEINASE;
EID: 58749083531     PISSN: 18607179     EISSN: 18607187     Source Type: Journal    
DOI: 10.1002/cmdc.200800321     Document Type: Article
Times cited : (72)
References (28)
  • 1
    • 0001191318 scopus 로고
    • Eds, R. E. Banks, B. E. Smart, J.C. Tatlow, Plenum, New York
    • a) B. E. Smart in Organofluorine Chemistry (Eds.: R. E. Banks, B. E. Smart, J.C. Tatlow), Plenum, New York, 1994, pp. 57-88;
    • (1994) Organofluorine Chemistry , pp. 57-88
    • Smart, B.E.1
  • 5
    • 34848848499 scopus 로고    scopus 로고
    • K. Müller, C. Faeh, F. Diederich, Science 2007, 317, 1881-1886; Although the van der Waals of trifluoromethyl and ethyl groups are similar, the shape of the two groups are very different. The same is true for the shapes of trifluoromethyl and isopropyl groups. For a discussion about this issue, see:
    • a)K. Müller, C. Faeh, F. Diederich, Science 2007, 317, 1881-1886; Although the van der Waals volumes of trifluoromethyl and ethyl groups are similar, the shape of the two groups are very different. The same is true for the shapes of trifluoromethyl and isopropyl groups. For a discussion about this issue, see:
  • 9
    • 11244267140 scopus 로고    scopus 로고
    • c) M. Zanda, New J. Chem. 2004, 28, 1401-1411.
    • (2004) New J. Chem , vol.28 , pp. 1401-1411
    • Zanda, M.1
  • 10
    • 11844255399 scopus 로고    scopus 로고
    • Importantly, our goal was to evaluate the bioisosterism of the CF 3 group and not its size, shape, or other physicochemical properties. Bioi-sosterism can be defined as the property according to which substitu-ents or groups with similar physical or chemical properties impart similar biological properties to a chemical compound. As correctly evidenced by two of the referees of this work, a series of IC50 values for the inhibition of an enzyme could not be used to measure the steric size of the CF3 group, as it would imply a significant oversimplification, ignoring issues such as lipophilicity, hydrophobicity, influence of dipolar interactions involving fluorine, kinetics of inhibition, possible multiple or alternate binding modes, the impact of electronic interactions, and entropic contributions to steric For a review on the concept and use of bioisosterism in medicinal chemistry, see: L. Moreira, E. J. Barreiro, Curr. Med. Chem. 2005
    • 3 group, as it would imply a significant oversimplification, ignoring issues such as lipophilicity, hydrophobicity, influence of dipolar interactions involving fluorine, kinetics of inhibition, possible multiple or alternate binding modes, the impact of electronic interactions, and entropic contributions to steric volume. For a review on the concept and use of bioisosterism in medicinal chemistry, see: L. Moreira, E. J. Barreiro, Curr. Med. Chem. 2005, 12, 23-49.
  • 28
    • 58749116510 scopus 로고    scopus 로고
    • An interpretation of this strong effect of the para substituent on the 5- benzyl residue of the barbiturates, which should occupy the S2′ subsite of the enzymes, is difficult in the absence of structural data on the binding of these ligands to MMPs. Attempts to obtain the crystallo- graphic structure of CF3-barbiturates such as 1 in complex with a truncated catalytic domain of MMP-9 have been so far unsuccessful. Only a few crystallographic structures of MMP-9 complexes have been reported owing to the instability of full-length MMP-9. See also reference [6a
    • 3-barbiturates such as 1 in complex with a truncated catalytic domain of MMP-9 have been so far unsuccessful. Only a few crystallographic structures of MMP-9 complexes have been reported owing to the instability of full-length MMP-9. See also reference [6a] .

* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.