412336-07-3Relevant articles and documents
AMINO-QUINOLINES AS KINASE INHIBITORS
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Paragraph 0180; 0182, (2015/09/23)
Disclosed are quinoline compounds having the formula: wherein R1, R2 and A are as defined herein, and methods of making and using the same.
Discovery of a New Class of Anilinoquinazoline Inhibitors with High Affinity and Specificity for the Tyrosine Kinase Domain of c-Src
Plé, Patrick A.,Green, Tim P.,Hennequin, Laurent F.,Curwen, Jon,Fennell, Michael,Allen, Jack,Lambert-Van Der Brempt, Christine,Costello, Gerard
, p. 871 - 887 (2007/10/03)
Deregulated activity of the nonreceptor tyrosine kinase c-Src is believed to result in signal transduction, cytoskeletal and adhesion changes, ultimately promoting a tumor-invasive phenotype. We report here the discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of the c-Src enzyme. Special attention was directed toward finding inhibitors selective against KDR tyrosine kinase in order to ensure that the in vivo profile of a specific Src inhibitor could be determined. The 4-aminobenzodioxole quinazoline series gave compounds with excellent potency and selectivity. The most interesting compounds were evaluated in vivo and displayed good pharmacokinetics following oral dosing. Compounds such as the aminobenzodioxoles were shown to be potent inhibitors of tumor growth in a c-Src-transformed 3T3 xenograft model in vivo, resulting in more than 90% growth inhibition at doses as low as 6 mg/kg po once daily. Src tyrosine kinase inhibitors such as these may provide a novel therapeutic modality for targeting cancer invasion and metastasis.
CONFORMATIONAL ANALYSIS OF ORGANIC CARBONYL COMPOUNDS. PART 4. A (1)H AND (13)C NUCLEAR MAGNETIC RESONANCE STUDY OF FORMYL AND ACETYL DERIVATIVES OF BENZOFURAN
Benassi, Rois,Folli, Ugo,Iarossi, Dario,Schenetti, Luisa,Taddei, Ferdinando
, p. 1479 - 1486 (2007/10/02)
A conformational study of formyl and acetyl derivatives of benzofuran provides evidence that in the case of 2- and 7-derivatives the E,Z-conformational mixture is solvent dependent, the Z-form prevailing in solvents with higher polarity.The presence of the same substituents in the 3- and 4-position gives compounds with predominantly Z-conformation and no change is caused by solvents.These results show an interestingly different behaviour by carbonyl derivatives of benzofuran with respect to the same benzothiophene derivatives.The conformational analysis was carried out by the n.m.r. method by employing (1)H and (13)C chemical shifts, long-range proton-proton coupling constants, and lanthanide-induced shifts (LIS) simulation.For the derivatives substituted in position 7, the LIS method is not a suitable approach for the determination of the conformer populations since, in solution, a chelate is formed where bonding of Eu to the oxygen atoms of the carbonyl and of the heterocyclic ring stabilizes the Z-form.A quantitative approach for determining the relative conformer populations of benzofuran-7-carbaldehyde was set up by statistical manipulation of long-range proton-proton coupling constants, proton chemical shifts, and the classical of dielectrics.
