PL EN


Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników
2012 | 1 | 1 |
Tytuł artykułu

Towards drugging the ‘undruggable’: enhancing the scaffold diversity of synthetic small molecule screening collections using diversity-oriented synthesis

Treść / Zawartość
Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Medicinal chemistry research has traditionally focused upon a limited set of biological targets. Many other human disease-related targets have been termed ‘undruggable’ as they have proved largely impervious to modulation by small molecules. However, it is becoming increasingly evident that such targets can indeed be modulated; they are simply being challenged with the wrong types of molecules. Traditionally, screening libraries were composed of large numbers of structurally similar compounds. However, library size is not everything; the structural diversity of the library, which is largely dictated by the range of molecular scaffolds present, is crucial. Diversity-oriented synthesis (DOS) generates small molecule libraries with high levels of scaffold, and thus structural, diversity. Such collections should provide hits against a broad range of targets with high frequency, including ‘undruggable’ targets. Examples in the area of scaffold diversity generation taken from the author’s laboratories are given.
Wydawca

Rocznik
Tom
1
Numer
1
Opis fizyczny
Daty
otrzymano
2013-01-12
zaakceptowano
2013-02-04
online
2013-02-28
Twórcy
  • Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK
  • Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK, spring@ch.cam.ac.uk
Bibliografia
  • [1] Galloway W.R.J.D., Isidro-Llobet A., Spring D. R., Nat. Commun. 2010, 1, 80.[PubMed]
  • [2] O’Connor C. J., Beckmann H. S. G., Spring D.R., Chem. Soc. Rev. 2012, 41, 4444.
  • [3] Diversity-Oriented Synthesis, O’Connell K. M. G., Galloway W. R. J. D., Ibbeson B. M., Isidro-Llobet A., O’ Connor C. J., Spring D. R. Book chapter in “Solid-Phase Organic Synthesis: Concepts, Strategies, and Applications”, ed. P. H. Toy, Y. Lam, 2012, Wiley, pp 131-150
  • [4] Galloway W. R. J. D., Bender A., Welch M.,Spring D.R., Chem. Comm. 2009, 2446.
  • [5] Walsh D. P., Chang Y. T., Chem. Rev. 2006, 106, 2476.[PubMed]
  • [6] Galloway W. R. J. D., Spring D.R., Exp. Opin. Drug Discov. 2009, 4, 467.
  • [7] Galloway W. R. J. D., Spring D. R., Nature 2011, 470, 43.
  • [8] Burke M. D., Schreiber S. L., Angew. Chem. Int. Ed. 2004, 43, 46.
  • [9] Burke M. D., Berger E. M., Schreiber S. L., Science, 2003, 302, 613-618.
  • [10] Schreiber S.L., Nature, 2009, 457, 153-154.
  • [11] Sauer W. H., Schwarz M. K., J. Chem. Inf. Comput. Sci. 2003, 43, 987.
  • [12] Dai, Wei-Min, Diversity Oriented Synthesis 2012, doi: 10.2478/dos-2012-0003.[Crossref]
  • [13] Langdon S. R., Brown N., Blagg J. J. Chem. Inf. Model. 2011, 51, 2174.
  • [14] Lipinski C., Hopkins A., Nature 2004, 432, 855.
  • [15] Basso, A., Diversity Oriented Synthesis 2012, doi: 10.2478/ dos-2012-0001.[Crossref]
  • [16] Altmann K. H., Buchner J., Kessler H., Diederich F., Krautler B., Lippard S., Liskamp R., Muller K., Nolan E.M., Samori B., Schneider G., Schreiber S. L., Schwalbe H., Toniolo C., van Boeckel C. A., Waldmann H.,Walsh C. T., ChemBioChem 2009, 10, 16.[PubMed]
  • [17] Shelat A. A., Guy R.K., Nat. Chem. Biol. 2007, 3, 442.[PubMed]
  • [18] Lipkus A. H., Yuan Q., Lucas K. A., Funk S. A., Bartelt III W.F., Schenck R. J., Trippe A. J., J. Org. Chem. 2008, 73, 4443.
  • [19] Pitt W. R., Parry D. M., Perry B. G., Groom C. R., J. Med. Chem. 2009, 52, 2952.
  • [20] Lee D., Sello J.K., Schreiber S.L., Org. Lett. 2000, 2, 709.[PubMed]
  • [21] Schreiber S.L., Science 2000, 287, 1964.
  • [22] Valot G., Garcia J., Duplan V., Serba C., Barluenga S., Winssinger N., Angew. Chem. Int. Ed. 2012, 51, 5391.
  • [23] Oguri H., Hiruma T., Yamagishi Y., Oikawa H., Ishiyama A., Otoguro K., Yamada H., Ōmura S., J. Am. Chem. Soc. 2011, 133, 7096.
  • [24] Oh S., Park S. B., Chem. Comm. 2011, 12754
  • [25] Wyatt E. E., Fergus S., Galloway W. R. J. D., Bender A., Fox D. J., Plowright A. T., Jessiman A. S., Welch M., Spring D.R., Chem. Comm. 2006, 3296.
  • [26] Thomas G. L., Spandl R. J., Glansdorp F. G., Welch M., Bender A., Cockfield J., Lindsay J.A., Bryant C., Brown D. F. J., Loiseleur O., Rudyk H., Ladlow M., Spring D. R., Angew. Chem. Int. Ed. 2008, 47, 2808.
  • [27] Wyatt E. E., Galloway W. R. J. D., Thomas G. L., Welch M., Loiseleur O., Plowright A. T., Spring D. R., Chem. Comm. 2008, 4962.
  • [28] O’Connell K. M., Beckmann H. S., Laraia L., Horsley H. T., Bender A., Venkitaraman A. R., Spring D. R., Org. Biomol. Chem. 2012, 10, 7545.
  • [29] Driggers E. M., Hale S. P., Lee J., Terrett N. K., Nat. Rev. 2008, 7, 608.
  • [30] Madsen C. M., Clausen M. H., Eur. J. Org. Chem. 2011, 3107.
  • [31] Wessjohann L. A., Ruijter E., Garcia-Rivera D., Brandt W., Mol. Divers. 2005, 9, 171.[PubMed]
  • [32] Wessjohann L. A., Voigt B., Rivera D. G., Angew. Chem. Int. Ed. 2005, 44, 4785.
  • [33] Marcaurelle L.A., Comer E., Dandapani S., Duvall J. R., Gerard B., Kesavan S., Lee M. D.t., Liu H., Lowe J. T., Marie J. C., Mulrooney C. A., Pandya B. A., Rowley A., Ryba T. D., Suh B. C., Wei J., Young D. W., Akella L.B., Ross N. T., Zhang Y. L., Fass D. M., Reis S. A., Zhao W. N., Haggarty S. J., Palmer M., Foley M. A., J. Am. Chem. Soc. 2010, 132, 16962.
  • [34] Kopp F., Stratton C. F., Akella L. B., Tan D. S., Nat. Chem. Biol 2012, 8, 358.
  • [35] Isidro-Llobet A., Murillo T., Bello P., Cilibrizzi A., Hodgkinson J. T., Galloway W. R. J. D., Bender A., Welch M., Spring D. R., Proc. Natl. Acad. Sci. U. S. A 2011, 108, 6793.
  • [36] Vagner J., Qu, H., Hruby, V. J., Curr. Opin. Chem. Biol. 2008, 12, 292.
  • [37] Williams R. M., Durham, C. A., Chem. Rev. 1988, 88, 511.
  • [38] Campbell J., Blackwell H. E., J. Comb. Chem. 2009, 11, 1094.
  • [39] Hamann M. T., Curr. Opin. Molec. Ther. 2004, 6, 657.
  • [40] Magauer T., Martin H. J., Mulzer J. Angew. Chem. Int. Ed. 2009, 48, 6032.
  • [41] Nahrwold M., Bogner T., Eissler S., Verma S., Sewald N., Org. Lett. 2010, 12, 1064.[PubMed]
  • [42] Nielsen T. E., Schreiber S. L., Angew, Chem. Int. Ed. 2008, 47, 48.
  • [43] Kenwright J. L., Galloway W. R. J. D., Blackwell D. T., Isidro- Llobet A., Hodgkinson J., Wortmann L., Bowden S. D., Welch M., Spring D. R., Chem. Eur. J. 2011, 17, 2981.
  • [44] Rousseau G., Tetrahedron 1995, 51, 2777.
  • [45] Grant S. M., Faulds, D., Drugs 1992, 43, 873.[PubMed]
  • [46] Kawashima K., Saraie T., Kawano Y., Ishiguro T., Chem. Pharm. Bull. 1978, 26, 942.
  • [47] Spandl R. J., Rudyk H., Spring D. R., Chem. Comm. 2008, 3001.
  • [48] Morton D., Leach S., Cordier C., Warriner S., Nelson A., Angew. Chem. Int. Ed. 2009, 48, 104.
  • [49] Galloway W. R. J. D., Diaz-Gavilan M., Isidro-Llobet A., Spring D. R., Angew. Chem. Int. Ed. 2009, 48, 1194.
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.-psjd-doi-10_2478_dos-2013-0001
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.