A novel series of positive modulators of the AMPA receptor: Discovery and structure based hit-to-lead studies

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 19, 2010, Pages 5753-5756

  Jamieson, Craig ^a   Basten, Stephanie ^a   Campbell, Robert A ^a   Cumming, Iain A ^a   Gillen, Kevin J ^a   Gillespie, Jonathan ^a   Kazemier, Bert ^a   Kiczun, Michael ^a   Lamont, Yvonne ^a   Lyons, Amanda J ^a   MacLean, John K F ^a   Moir, Elizabeth M ^a   Morrow, John A ^a   Papakosta, Marianthi ^a   Rankovic, Zoran ^a   Smith, Lynn ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Allosteric modulator; AMPA receptor; Hit to lead; SBDD

Indexed keywords

AMINE; AMPA RECEPTOR; AMPA RECEPTOR AGONIST; AMPA RECEPTOR ANTAGONIST; TETRAHYDROBENZOTHIOPHENE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG HALF LIFE; DRUG PENETRATION; DRUG POTENCY; DRUG SOLUBILITY; DRUG STABILITY; HUMAN; NONHUMAN; PHYSICAL CHEMISTRY; PROTEIN PROTEIN INTERACTION; RAT;

ALLOSTERIC REGULATION; ANIMALS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INDAZOLES; MICROSOMES; PROTEIN STRUCTURE, TERTIARY; RATS; RECEPTORS, AMPA; THIOPHENES;

EID: 77957605595     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.07.138     Document Type: Article

References (13)

1. J.N.C. Kew, and J.A. Kemp Psychopharmacology 179 2005 4
2. S. Marenco, and D.R. Weinberger CNS Drugs 20 2006 173
3. J. Zarate, and H.K. Manji Exp. Neurol. 211 2008 7
4. M.L. Mayer, and N. Armstrong Annu. Rev. Physiol. 66 2004 161
5. N. Armstrong, Y. Sun, G.Q. Chen, and E. Gouaux Nature 395 1998 913
6. A.I. Sobolevsky, M.P. Rosconi, and E. Gouaux Nature 462 2009 745
7. 2 and 10 mM glucose) to each well and the ensuing response was monitored on FLEXstation.
8. Crystals were grown as described in Ref. 5. Co-crystals were prepared by soaking test compound (100 mM) with crystals for 24 h prior to isolation and data collection. Coordinates and structure factors have been deposited in the Protein Data Bank for complexes of compounds 1 (3O28), 15 (3O29) and 16 (3O2A).
9. The Pymol Molecular Graphics System (DeLano Scientific, Palo Alto, CA, 2002) was used to generate Figures 1-3.
10. Maclean, J. K. F.; Kazemier, B. J. Mol. Biol., in press.
11. Y. Sun, R. Olson, M. Horning, N. Armstrong, M. Mayer, and E. Gouaux Nature 417 2002 245
12. C.P. Ptak, A.H. Ahmed, and R.E. Oswald Biochemistry 48 2009 8594
13. K. Gewald, E. Schinke, and H. Boettcher Chem. Ber. 99 1966 94