Novel cinnoline-based inhibitors of LRRK2 kinase activity

Bioorganic and Medicinal Chemistry Letters

Volumn 23, Issue 1, 2013, Pages 71-74

  Garofalo, Albert W ^a   Adler, Marc ^a   Aubele, Danielle L ^a   Bowers, Simeon ^a   Franzini, Maurizio ^a   Goldbach, Erich ^a   Lorentzen, Colin ^a,b   Neitz, R Jeffrey ^a,c   Probst, Gary D ^a   Quinn, Kevin P ^a   Santiago, Pam ^a   Sham, Hing L ^a   Tam, Danny ^a   Truong, Anh P ^a   Ye, Xiaocong M ^a   Ren, Zhao ^a  

^a ELAN PHARMACEUTICALS   (United States)

^b NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Kinase inhibitors; Leucine rich repeat kinase 2; LRRK2; Parkinson's disease

Indexed keywords

CINNOLINE 3 CARBOXAMIDE; LEUCINE RICH REPEAT KINASE 2; PROTEIN SERINE THREONINE KINASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CELL ASSAY; CENTRAL NERVOUS SYSTEM; CHEMICAL ANALYSIS; DRUG ACTIVITY; DRUG DETERMINATION; DRUG PENETRATION; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION;

AMIDES; ANIMALS; BINDING SITES; HEK293 CELLS; HETEROCYCLIC COMPOUNDS, 2-RING; HUMANS; MICE; MOLECULAR DOCKING SIMULATION; MUTATION; PROTEIN BINDING; PROTEIN KINASE INHIBITORS; PROTEIN STRUCTURE, TERTIARY; PROTEIN-SERINE-THREONINE KINASES; TRANSFECTION;

EID: 84871000670     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.11.021     Document Type: Article

References (14)

1. M. Funayama, K. Hasegawa, and H. Kowa Ann. Neurol. 51 2002 296
2. E. Greggio, and M.R. Cookson ASN Neurochem. 1 2009 13
3. D.G. Healy, M. Falchi, and S.S. O'Sullivan Lancet Neurol. 7 2008 583
4. J.C. Latourell, M. Sun, and M.F. Lew BMC Med. 6 2008 32
5. A.B. West, D.J. Moore, and S. Biskup Proc. Nat. Acad. Sci. 102 2005 16842
6. E. Greggio, S. Jain, and A. Kingsbury Neurobiol. Dis. 23 2006 329
7. M. Jaleel, R.J. Nichols, and M. Deak Biochem. J. 405 2007 307
8. Homogeneous time-resolved fluorescence (HTRF) assay using GST-LRRK2. Detection was done using biotinylated LRRKtide, Eu(K)-Ab (p-Moesin)/SA-XL665 measured at 620 and 665 nm.
9. T.L. Smalley Jr., S.D. Chamberlain, and W.Y. Mills Bioorg. Med. Chem. Lett. 17 2007 6257
10. It has been speculated that intramolecular hydrogen bonds can account for the high permeability of compounds with non-optimal physicochemical properties. See: A. Alex, D.S. Millan, and M. Perez Med. Chem. Commun. 2 2011 669
11. D.A. Scott, L.A. Dakin, and D.J. Del Valle Bioorg. Med. Chem. Lett. 21 2011 1382
12. R.L. Hudkins, J.L. Diebold, and M. Tao J. Med. Chem. 51 2008 5680
13. T. Takimura, K. Kamata, and K. Fukasawa Acta Crystallogr. D. Biol. Crystallogr. D66 2010 577
14. N. Dzamko, M. Deak, and F. Hentati Biochem. J. 430 2010 405