419557-85-0Relevant academic research and scientific papers
The discovery of the potent aurora inhibitor MK-0457 (VX-680)
Bebbington, David,Binch, Hayley,Charrier, Jean-Damien,Everitt, Simon,Fraysse, Damien,Golec, Julian,Kay, David,Knegtel, Ronald,Mak, Chau,Mazzei, Francesca,Miller, Andrew,Mortimore, Michael,O'Donnell, Michael,Patel, Sanjay,Pierard, Francoise,Pinder, Joanne,Pollard, John,Ramaya, Sharn,Robinson, Daniel,Rutherford, Alistair,Studley, John,Westcott, James
scheme or table, p. 3586 - 3592 (2010/03/31)
The identification of a novel series of Aurora kinase inhibitors and exploitation of their SAR is described. Replacement of the initial quinazoline core with a pyrimidine scaffold and modification of substituents led to a series of very potent inhibitors of cellular proliferation. MK-0457 (VX-680) has been assessed in Phase II clinical trials in patients with treatment-refractory chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) containing the T315I mutation.
Discovery of potent cyclic GMP phosphodiesterase inhibitors. 2-Pyridyl- and 2-imidazolylquinazolines possessing cyclic GMP phosphodiesterase and thromboxane synthesis inhibitory activities
Lee,Konishi,Yu,Miskowski,Riviello,Macina,Frierson,Kondo,Sugitani,Sircar,Blazejewski
, p. 3547 - 3557 (2007/10/03)
Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2- phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP- PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme assay than the well-known inhibitor zaprinast. The 6-substituted derivatives of 2-(3- pyridyl)quinazoline 84 and 2-(imidazol-1-yl)quinazoline 86 exhibited more than 1000-fold selectivity for PDE V over the other four PDE isozymes. In addition, cGMP-PDE inhibitors 64, 65, and 73 were found to have an additional property of thromboxane synthesis inhibitory activity.
