Designing rapid onset selective serotonin re-uptake inhibitors. Part 3: Site-directed metabolism as a strategy to avoid active circulating metabolites: Structure-activity relationships of (thioalkyl)phenoxy benzylamines

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 19, 2008, Pages 5303-5306

  Middleton, Donald S ^a   Andrews, Mark ^a   Glossop, Paul ^a   Gymer, Geoffrey ^a   Hepworth, David ^a   Jessiman, Alan ^a   Johnson, Patrick S ^a   MacKenny, Malcolm ^a   Stobie, Alan ^a   Tang, Kim ^a   Morgan, Paul ^a   Jones, Barry ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

Site directed metabolism; SSRI; Volume of distribution

Indexed keywords

ALKYL GROUP; BENZYLAMINE DERIVATIVE; DIPHENYL ETHER; DRUG METABOLITE; SEROTONIN UPTAKE INHIBITOR; SULFONAMIDE;

ANIMAL CELL; ARTICLE; DEMETHYLATION; DISTRIBUTION VOLUME; DRUG DESIGN; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; HYDROGEN BOND; IC 50; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

BENZYLAMINES; COMBINATORIAL CHEMISTRY TECHNIQUES; HUMANS; MOLECULAR STRUCTURE; PHENYL ETHERS; SEROTONIN UPTAKE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 52249122619     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.08.040     Document Type: Article

References (15)

1. Middleton D.S., Andrews M.D., Glossop P., Gymer G., Jessiman A., Johnson P.J., MacKenny M., Pitcher M.J., Rooker T., Stobie A., Tang K., and Morgan P. Bioorg. Med. Chem. Lett. 16 (2006) 1434
2. Middleton D.S., Andrews M., Glossop P., Gymer G., Hepworth D., Jessiman A., Johnson P.S., MacKenny M., Pitcher M.J., Rooker T., Stobie A., Tang K., and Morgan P. Bioorg. Med. Chem. Lett. 18 (2008) 4018
3. Andrews, M. D.; Hepworth, D.; Middleton, D. S.; Stobie, A. US 6 448 293.
4. Adam, M. D.; Andrews, M. D.; Gymer, G. E.; Hepworth, D.; Howard, H. R., Jr.; Middleton, D. S.; Stobie, A. WO2002083643.
5. Whitlock G.A., Fish P.V., and Blagg J. Bioorg. Med. Chem. Lett. 18 (2008) 596
6. Ruigt, G. S. F.; Leysen, D.; Wieringa, J. H. US 5190965.
7. Vercouillie J., Deuther-Conrad W., Scheunemann M., Emond P., Fischer S., Funke U., Steinbach J., Guilloteau D., and Brust P. Bioorg. Med. Chem. Lett. 17 (2007) 4991 and references cited therein
8. Ly K.S., Letavic M.A., Keith J.M., Miller J.M., Stocking E.M., Barbier A.J., Bonaventure P., Lord B., Jiang X., Boggs J.D., Dvorak L., Miller K., Nepomuceno D., Wilson S.J., and Carruthers N.I. Bioorg. Med. Chem. Lett. 18 (2008) 39 and references cited therein
9. Walker D.K., Humphrey M.J., and Smith D.A. Xenobiotica 24 (1994) 243 and references cited therein
10. Part of this work has been described previously, Middleton D. S. In 230th ACS National Meeting Washington, DC, Aug 2005; Paper 228.
11. Krueger S.K., and Williams D.E. Pharmacol. Ther. 106 (2005) 357
12. de Groot M.J., Ackland M.J., Horne V.A., Alex A.A., and Jones B.C. J. Med. Chem. 42 (1999) 4062
13. de Groot M.J., Ackland M.J., Horne V.A., Alex A.A., and Jones B.C. J. Med. Chem. 42 (1999) 1515
14. Rendic S., and Di Carlo F.J. Drug Metab. Rev. 19 (1997) 413
15. Coutts R.T., Su P., and Baker G.B. J. Pharmacol. Toxicol. Methods 31 (1994) 177