Rapid assessment of a novel series of selective CB2 agonists using parallel synthesis protocols: A Lipophilic Efficiency (LipE) analysis

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 15, 2009, Pages 4406-4409

  Ryckmans, Thomas ^a   Edwards, Martin P ^b   Horne, Val A ^a   Correia, Ana Monica ^a   Owen, Dafydd R ^a   Thompson, Lisa R ^a   Tran, Isabelle ^a   Tutt, Michelle F ^a   Young, Tim ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

^b PFIZER INC   (United States)

Author keywords

Agonist; CB2; LiPE; Lipophilicity; Parallel synthesis

Indexed keywords

AMIDE; CANNABINOID 2 RECEPTOR AGONIST; CANNABINOID RECEPTOR AGONIST; CARBAMIC ACID; PYRIDINE DERIVATIVE; SULFONAMIDE; UNCLASSIFIED DRUG; UREA;

ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; LIPOPHILICITY; MOLECULAR WEIGHT; TEMPERATURE MEASUREMENT;

ANIMALS; BINDING SITES; CHEMISTRY, PHARMACEUTICAL; COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG DESIGN; INHIBITORY CONCENTRATION 50; LIGANDS; MICROSOMES, LIVER; MODELS, CHEMICAL; MOLECULAR STRUCTURE; NITROGEN; RATS; RECEPTOR, CANNABINOID, CB2; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 67649962669     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.05.062     Document Type: Article

References (16)

1. Grotenhermen F. Curr. Drug Targets CNS Neurol. Disord. 4 (2005) 507
2. Yao B.B., Hsieh G.C., Frost J.M., Fan Y., Garrison T.R., Daza A.V., Grayson G.K., Zhu C.Z., Pai M., Chandran P., Salyers A.K., Wensink E.J., Honore P., Sullivan J.P., Dart M.J., and Meyer M.D. Br. J. Pharmacol. 153 (2008) 367
3. Hosking R.D., and Zajicek J.P. Br. J. Anaesth. 101 (2008) 59
4. Malan T.P., Ibrahim M.M., Lai J., Vanderah T.W., Makriyannis A., and Porreca F. Curr. Opin. Pharmacol. 3 (2003) 62
5. Whiteside G.T., Lee G.P., and Valenzano K.J. Curr. Med. Chem. 14 (2007) 917
6. Ando, K.; Kawai, M.; Masuda, T.; Omura, H. WO07102059, 2006.
7. Kelley J.L., Koble C.S., Davis R.G., McLean E.W., Soroko F.E., and Cooper B.R. J. Med. Chem. 38 (1995) 4131
8. Leeson P.D., and Springthorpe B. Nat. Rev. Drug Disc. 6 (2007) 881
9. Di Marzo V. Rev. Physiol. Biochem. Pharmacol. 160 (2006) 1
10. Uetrecht J. Curr. Opin. Drug Disc. Devel. 4 (2001) 55
11. Uetrecht J. Chem. Res. Toxicol. 21 (2008) 84
12. Edwards, M. P., unpublished results. See also reference 8 for a very similar approach named LLE.
13. Kania R.S. In: Stafford J.A., and Li R. (Eds). Kinase Inhibitor Drugs (2009), John Wiley and Sons Chapter 7
14. Hughes J.D., Blagg J., Price D.A., Bailey S., DeCrescenzo G.A., Devraj R.V., Ellsworth E., Fobian Y.M., Gibbs M.E., Gilles R.W., Greene N., Huang E., Krieger-Burke T., Loesel J., Wager T., Whiteley L., and Zhang Y. Bioorg. Med. Chem. Lett. 18 (2008) 4872
15. 50 was determined via a sigmodal plot of the cAMP response versus log compound concentration.
16. See Supplementary data.