AIM: To characterize the structural features of quinazoline-based Aurora B inhibitors that influence its inhibitor activity. METHODS: Two geometrical methods, Method 1 and Method 2, were used to develop the 3D-QSAR models. The most active ligand was used as the template for the alignment of all the ligands in Method 1, and a conformer of the cocrystal ligand was used as the template for the alignment of all the ligands in Method 2. RESULTS: The models suggest that highly active ligands can be designed by varying the R1 substituent at position 7 of the quinazoline ring with positively charged, bulky, hydrophobic groups, while bulky and hydrophobic groups around the thiazole ring are desirable for higher activity. CONCLUSION: This study emphasizes that the bioactive conformer is rather different from the minima. The steric, electrostatic, and hydrophobic field effects contribute to its inhibitory activity.
AIM: To characterize the structural features of quinazoline-based Aurora B inhibitors that influence its inhibitor activity. METHODS: Two geometrical methods, Method 1 and Method 2, were used to develop the 3D-QSAR models. The most active ligand was used as the template for the alignment of all the ligands in Method 1, and a conformer of the cocrystal ligand was used as the template for the alignment of all the ligands in Method 2. RESULTS: The models suggest that highly active ligands can be designed by varying the R1 substituent at position 7 of the quinazoline ring with positively charged, bulky, hydrophobic groups, while bulky and hydrophobic groups around the thiazole ring are desirable for higher activity. CONCLUSION: This study emphasizes that the bioactive conformer is rather different from the minima. The steric, electrostatic, and hydrophobic field effects contribute to its inhibitory activity.
Authors: Nicola M Heron; Malcolm Anderson; David P Blowers; Jason Breed; Jonathan M Eden; Stephen Green; George B Hill; Trevor Johnson; Frederic H Jung; Helen H J McMiken; Andrew A Mortlock; Andrew D Pannifer; Richard A Pauptit; Jennifer Pink; Nicola J Roberts; Siân Rowsell Journal: Bioorg Med Chem Lett Date: 2005-12-05 Impact factor: 2.823
Authors: Andrew A Mortlock; Kevin M Foote; Nicola M Heron; Frédéric H Jung; Georges Pasquet; Jean-Jacques M Lohmann; Nicolas Warin; Fabrice Renaud; Chris De Savi; Nicola J Roberts; Trevor Johnson; Cyril B Dousson; George B Hill; David Perkins; Glenn Hatter; Robert W Wilkinson; Stephen R Wedge; Simon P Heaton; Rajesh Odedra; Nicholas J Keen; Claire Crafter; Elaine Brown; Katherine Thompson; Stephen Brightwell; Liz Khatri; Madeleine C Brady; Sarah Kearney; David McKillop; Steve Rhead; Tony Parry; Stephen Green Journal: J Med Chem Date: 2007-03-21 Impact factor: 7.446
Authors: Graham M T Cheetham; Ronald M A Knegtel; Joyce T Coll; Suzanne B Renwick; Lora Swenson; Peter Weber; Judith A Lippke; Douglas A Austen Journal: J Biol Chem Date: 2002-09-16 Impact factor: 5.157
Authors: Anjali Pandey; Deborah L Volkots; Joseph M Seroogy; Jack W Rose; Jin-Chen Yu; Joseph L Lambing; Athiwat Hutchaleelaha; Stanley J Hollenbach; Keith Abe; Neill A Giese; Robert M Scarborough Journal: J Med Chem Date: 2002-08-15 Impact factor: 7.446
Authors: Salvatore Ulisse; Jean-Guy Delcros; Enke Baldini; Matteo Toller; Francesco Curcio; Laura Giacomelli; Claude Prigent; Francesco S Ambesi-Impiombato; Massimino D'Armiento; Yannick Arlot-Bonnemains Journal: Int J Cancer Date: 2006-07-15 Impact factor: 7.396