379229-99-9

Upstream product

• 379228-29-2 7-(benzyloxy)-4-[(2-chloro-5-methoxyphenyl)amino]quinazolin-5-ol 
• 196207-16-6 4,6-bis(benzyloxy)-1H-indole-2,3-dione 
• 379228-32-7 methyl 2-amino-4,6-bis(benzyloxy)benzoate 
• 379228-31-6 2-amino-4,6-bis(benzyloxy)benzoic acid 
• 379228-33-8 5,7-bis(benzyloxy)quinazolin-4(3H)-one 
• 379230-01-0 7-(benzyloxy)-N-(2-chloro-5-methoxyphenyl)-5-isopropoxyquinazolin-4-amine 

Relevant academic research and scientific papers

N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy] -5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor

Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. AZD0530 displays excellent pharmacokinetic parameters in animal preclinically and in man (t1/2 = 40 h). AZD0530 is a potent inhibitor of tumor growth in a c-Src-transfected 3T3-fibroblast xenograft model in vivo and led to a significant increase in survival in a highly aggressive, orthotopic model of human pancreatic cancer when dosed orally once daily. AZD0530 is currently undergoing clinical evaluation in man.

QUINAZOLINE DERIVATIVES FOR THE TREATMENT OF TUMOURS

The invention concerns quinazoline derivatives of Formula (I) wherein each of Q1, Z, m, R1, R2, R3 and Q2 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing 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