- TARGETED PROTEIN DEGRADATION OF PARP14 FOR USE IN THERAPY
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The present invention relates to quinazolinones and related compounds which degrade PARP14 and are useful, for example, in the treatment of cancer and inflammatory diseases.
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Page/Page column 69
(2021/01/22)
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- ANTIFUNGAL 5,6-DIHYDRO-4H-PYRROLO[1,2-A][1,4]-BENZODIAZEPINES AND 6H-PYRROLO[1,2-A][1,4]BENZODIAZEPINES SUBSTITUTED WITH PHENYL DERIVATIVES
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The present invention is concerned with novel antifungal 5,6-dihydro-4H-pyrrolo-[1,2-a][1,4]benzodiazepines and 6H-pyrrolo[1,2-a][1,4]benzodiazepines of Formula (I) wherein R1, R2, R3, R4, R5 and Rsu
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Page/Page column 43
(2012/06/15)
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- Process research and development for the kilogram manufacture of the SRC kinase inhibitor AZD0530
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Process research and development of a synthetic route towards a novel SRC kinase inhibitor is described. The Medicinal Chemistry route was very long and suffered from extensive use of chlorinated solvents and chromatography. A number of steps in the Medic
- Ford, J. Gair,Pointon, Simon M.,Powell, Lyn,Siedlecki, Paul S.,Baum, John,Chubb, Richard,Fieldhouse, Robin,Muxworthy, James,Nivlet, Alex,Stenson, Rachel,Warwick, Eleanor
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p. 1078 - 1087
(2011/04/12)
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- Pyrrolidine(thi)ones Substituted by Heterocyclic Substituents in The 3-Position
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Pyrrolidine(thi)one compounds substituted by heterocyclic substituents in the 3-position, their preparation and use in pharmaceutical compositions, in particular as immunomodulators for treatment and/or inhibition of inflammatory and autoimmune diseases and haematological-oncological diseases.
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- CHEMICAL PROCESS
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The present invention relates to chemical processes useful in the manufacture of the compound 4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]- 5-tetrahydropyran-4-yloxyquinazoline (the active entity within AZD0530), to intermed
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Page/Page column 52-53
(2008/06/13)
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- 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
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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.
- Hennequin, Laurent F.,Allen, Jack,Breed, Jason,Curwen, Jon,Fennell, Michael,Green, Tim P.,Lambert-Van Der Brempt, Christine,Morgentin, Rémy,Norman, Richard A.,Olivier, Annie,Otterbein, Ludovic,Plé, Patrick A.,Warin, Nicolas,Costello, Gerard
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p. 6465 - 6488
(2007/10/03)
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