- AMINO-QUINOLINES AS KINASE INHIBITORS
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Disclosed are quinoline compounds having the formula: wherein R1, R2 and A are as defined herein, and methods of making and using the same.
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Paragraph 0180; 0182
(2015/09/23)
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- Facile entry to 4- and 5-hydroxybenzofuran and to their amino derivatives
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An innovative one-step procedure for the synthesis of 4-hydroxybenzofuran and an improved synthesis of 5-hydroxybenzofuran is reported. Such compounds were also transformed into their amino derivatives via Smiles rearrangement with good to high overall yields. Copyright Taylor & Francis Group, LLC.
- Bonini, Carlo,Cristiani, Graziella,Funicello, Maria,Viggiani, Licia
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p. 1983 - 1990
(2007/10/03)
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- Discovery of a New Class of Anilinoquinazoline Inhibitors with High Affinity and Specificity for the Tyrosine Kinase Domain of c-Src
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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.
- Plé, Patrick A.,Green, Tim P.,Hennequin, Laurent F.,Curwen, Jon,Fennell, Michael,Allen, Jack,Lambert-Van Der Brempt, Christine,Costello, Gerard
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p. 871 - 887
(2007/10/03)
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- Quinazoline derivatives
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The invention concerns quinazoline derivatives of Formula (I) wherein each of m, R1, n, R2 and R3 have any of the meanings defined in the description; process for the preparation, pharmaceutical compositions them and their use in the manufacture of a medicament for use as an anti-invasive agent in the containment and/or treatment of solid tumour disease.
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- 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
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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.
- Benassi, Rois,Folli, Ugo,Iarossi, Dario,Schenetti, Luisa,Taddei, Ferdinando
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p. 1479 - 1486
(2007/10/02)
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