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SUBSTITUTED QUINOXALINES AND BENZOTRIAZINE P70S6 KINASE INHIBITORS
专利权人:
SENTINEL ONCOLOGY LIMITED
发明人:
BOYLE, Robert George,WALKER, David Winter
申请号:
EPEP2016/059091
公开号:
WO2016/170163A1
申请日:
2016.04.22
申请国别(地区):
WO
年份:
2016
代理人:
摘要:
The invention provides compounds that inhibit or modulate the activity of p70S6 kinase, the compounds being of the formula (0), or a salt, tautomer or N-oxide thereof wherein: X1 is N or N+(0-) X2 is N or CH Q1 is an optionally substituted C1-8 alkylene Q2 is a bond or an optionally substituted C1-8 alkylene group R1 is selected from hydrogen and a group Cy1 Cy1 is an optionally substituted 4 to 7 membered monocyclic non-aromatic carbocyclic or heterocyclic group containing 0, 1 or 2 heteroatom ring members selected from O and S and oxidised forms of S R2, R3 and R4 are the same or different and each is selected from hydrogen, fluorine, chlorine, C1-2 alkyl and C1-2 alkoxy, wherein each C1-2 alkyl and C1-2 alkoxy is optionally substituted with two or more fluorine atoms Ar1 is an optionally substituted monocyclic 5 or 6-membered aryl or heteroaryl ring containing 0, 1 or 2 heteroatom ring members selected from O, N and S, or a naphthyl ring Ar2 is an optionally substituted bicyclic 8 to 1 1 -membered heteroaryl group containing 1, 2, 3 or 4 heteroatom ring members selected from O, N and S. The compounds are useful in medicine, for example in the treatment of a disease or condition selected from cancers (e.g. triple negative breast cancer, brain tumours and brain metastases arising from non-brain cancers), neurodevelopmental diseases (e.g. Fragile X syndrome) and neurodegenerative diseases.Linvention concerne des composés qui inhibent ou modulent lactivité de la p70S6 kinase, les composés étant de formule (0) ou un sel, un tautomère ou un N-oxyde correspondant dans laquelle : X1 représente N ou N+(O-) X2 représente N ou C H Q1 représente un C1-8-alkylène éventuellement substitué Q2 représente une liaison ou un groupe C1-8-alkylène éventuellement substitué R1 est choisi parmi hydrogène et un groupe Cy1 Cy1 représente un groupe carbocyclique ou hétérocyclique, monocyclique, non aromatique, de 4 à 7 chainons, éventuellement substitué contenant 0, 1 ou 2 chaînons de
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