Bifunctional compounds capable of degrading androgen receptors

Abstract

A compound of Formula (1): or a pharmaceutically acceptable salt thereof, wherein: X1 is CH or N; weight O, 1 or 2; wherein: each R1 is a substituent on any C atom and is independently selected from F, C1, C1-3 alkyl and C1-3 alkoxy, wherein said C1-3 alkyl and C1-3 alkoxy may optionally be independently substituted with one or more F; RN is selected from H and Me; n is O, 1 or 2; m is O or 1; Q1 is CH or N; when nym are both other than O, Q2 is CH or N; when nym are both O, Q2 is CH; when n is O or 1, Q3 is CH; when n is 2 and Q2 is N, Q3 is CH; when n is 2 and Q2 is CH, Q3 is CH or O; R2a and R2b are substituents on the same C atom or on different C atoms other than Q1 or Q2, each independently selected from H, F and C1-3 alkyl, or R2a and R2b together form a -(CH2)r- group where res 1, 2 or 3; Q4 is a single bond or -NR4C(=0); R4 is H or Me; O, 1 or 2 of Y1, Y2, Y3, Y4 and Y5 is / are N, and are otherwise C; each R3 is a substituent of any C atom in Y1, Y2, Y3, Y4 and Y5, and is independently selected from F, C1, CN, C1-3 alkyl and C1-3 alkoxy, wherein said C1-3 alkyl and C1-3 alkoxy may be optionally independently substituted with one or more F; q is O, 1 or 2; wherein the Linker is attached to any available C atom in Y4 and Y5; The Linker is a saturated or partially or totally unsaturated framework comprising C and H atoms and at least one heteroatom, wherein said framework has binding endpoints 'a' and 'b' and a length of 5 to 26 atoms between 'a' and 'b'; wherein said framework may include one or more linear and / or branched chains and / or rings and is optionally substituted at any available C atom(s) by one or more F; and W is a cereblon-binding unit of the E3 ubiquitin ligase.