2-aminoquinazoline derivatives as P70S6 kinase inhibitors
Abstract:
The invention provides compound that inhibit or modulate the activity of p70S6 kinase, the compounds being of the formula (1): or a salt, tautomer or N-oxide thereof; wherein: one of Y and Z is R3 and the other is Ar2; Q1 is an optionally substituted C1-8 alkylene group; and wherein a carbon atom of the C1-8 alkylene group may optionally be replaced by a cyclopropane-1,1-diyl or cyclobutane-1,1-diyl group provided that the total number of carbon atoms in an alkylene group containing such a replacement does not exceed 8; Q2 is a bond or an optionally substituted C1-8 alkylene group R1 is selected from hydrogen, NRxRy and a group Cy1; Rx and Ry are each is selected from hydrogen, C1-4 hydrocarbyl or hydroxy-C1-4 hydrocarbyl; or NRxRy forms an optionally substituted 4 to 7-membered heterocyclic ring; Cy1 is an optionally substituted C-linked 3 to 7 membered monocyclic non-aromatic carbocyclic or heterocyclic; R2 and R4 are each is selected from hydrogen, fluorine, chlorine, optionally substituted C1-2 alkyl and optionally substituted C1-2 alkoxy; R3 is selected from hydrogen, fluorine, chlorine, optionally substituted C1-2 alkyl and optionally substituted C1-2 alkoxy; Ar1 is an optionally substituted monocyclic 5 or 6-membered aryl or heteroaryl ring; and Ar2 is an optionally substituted bicyclic 8 to 11-membered heteroaryl group. The compounds are useful in medicine, for example in the treatment of a disease or condition selected from cancers, neurodevelopmental diseases and neurodegenerative diseases.
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