Practical purification of hydrophilic fragments and lead/drug-like molecules by reverse phase flash chromatography: Tips, tricks and contemporary developments

Drug Discovery Today

Volumn 18, Issue 3-4, 2013, Pages 148-154

  Hobbs, Andrew N ^a   Young, Robert J ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BUFFER; LEAD; METHANOL; ORGANIC COMPOUND; SOLVENT; WATER;

AQUEOUS SOLUTION; CHROMATOGRAPHY; DRUG PURIFICATION; DRUG RETENTION; ELUTION; HYDROPHILICITY; MOLECULE; PH; REVERSE PHASE FLASH CHROMATOGRAPHY; REVIEW;

CHROMATOGRAPHY, REVERSE-PHASE; DRUG DISCOVERY; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; PHARMACEUTICAL PREPARATIONS;

EID: 84873091454     PISSN: 13596446     EISSN: 18785832     Source Type: Journal    
DOI: 10.1016/j.drudis.2012.09.006     Document Type: Review

References (22)

1. N.A. Meanwell Improving drug candidates by design: a focus on physicochemical properties as a means of improving compound disposition and safety Chem. Res. Toxicol. 24 2011 1420 1456
2. M. Waring Lipophilicity in drug discovery Expert Opin. Drug Discov. 5 2010 235 248
3. P.D. Leeson, and B. Springthorpe The influence of drug-like concepts on decision-making in medicinal chemistry Nat. Rev. Drug Discov. 6 2007 881 890
4. A.P. Hill, and R.J. Young Getting physical in drug discovery: a contemporary perspective on solubility and hydrophobicity Drug Discov. Today 15 2010 648 655
5. P.D. Leeson, and J.R. Empfield Reducing the risk of drug attrition associated with physicochemical properties Annu. Rep. Med. Chem. 45 2010 393 407
6. C.W. Murray, and D.C. Rees The rise of fragment-based drug discovery Nature Chem. 1 2009 187 192
7. D.A. Erlanson Fragment-based drug discovery J. Med. Chem. 47 2004 3463 3482
8. A. Nadin Lead-oriented synthesis: a new opportunity for synthetic chemistry Angew. Chem. Int. Ed. Engl. 51 2011 1114 1122
9. K. Valkó Chromatographic hydrophobicity index by fast-gradient RP-HPLC: a high-throughput alternative to log P/log D Anal. Chem. 69 1997 2022 2029
10. R.J. Young Getting physical in drug discovery II: the impact of chromatographic hydrophobicity measurements and aromaticity Drug Discov. Today 16 2011 822 830
11. M.M. Hann Molecular obesity, potency and other addictions in drug discovery MedChemComm. 2 2011 349 355
12. D.A. Wellings A Practical Handbook of Preparative HPLC 2006 Elsevier
13. W.C. Still Rapid chromatographic technique for preparative separations with moderate resolution J. Org. Chem. 43 1978 2923 2925
14. W.C. Stevens, and D.C. Hill General methods for flash chromatography using disposable columns Mol. Divers. 13 2009 247 252
15. S. Dubant, and B. Mathews Enabling facile, rapid and successful chromatographic Flash purification Chromatogr. Today 2 2009 10 12
16. Effective organic compound purification, guidelines and tactics for flash chromatography 4th edn 2010 Teledyne Isco
17. M. Rummel The Partition coefficient (log P), Distribution coefficient (log D) and acid dissociation constant (pKa): knowing your compound for solid-phase extraction method development in reversed-phase mode The Column 8 2012 2 7
18. T.H. Walter Mechanism of retention loss when C8 and C18 HPLC columns are used with highly aqueous mobile phases J. Chromatogr. A 1075 2005 177 183
19. N. Nagae The retention behaviour of reversed-phase HPLC columns with 100% aqueous mobile phase LC GC North America 20 2002 964 972
20. R.K. Henderson Expanding GSK's solvent selection guide-embedding sustainability into solvent selection starting at medicinal chemistry Green Chem. 13 2011 854 862
21. P. Appelblad T. Jonsson, A Practical Guide to HILIC 2008 Merck SeQuant AB
22. G.B. Alexander The solubility of amorphous silica in water J. Phys. Chem. 58 1954 453 455