JAK2 Inhibitors And Their Use As Pharmaceuticals

A compound of Formula (I)

• or a pharmaceutically acceptable salt or solvate or N-oxide thereof, wherein
• each of W1, W2, and W3 is independently N or CR8;
• each Z is independently O, S, SO2, NR4, NR9 or C(R8)2, wherein at least 3 Z are C(R8)2 and wherein at least one Z is NR4;
• each R8 is independently H, D, halogen, —OH, —CN, —NO2, —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, —ORa, —SRa, —NRcRd, —NRaRc, —C(O)Rb, —OC(O)Rb, —C(O)ORb, —C(O)NRcRd, —S(O)Rb, —S(O)2NRcRd, —S(O)(═NRb)Rb, —SF5, —P(O)RbRb, —P(O)(ORb)(ORb), —B(ORc)(ORd) or —S(O)2Rb;
• or any two R8 groups attached to the same carbon form ═O;
• or any two R8 groups attached to the same carbon form a 3-6 membered spirocycloalkyl or spiroheterocycloalkyl ring;
• or any two R8 groups attached to adjacent carbon atoms form a 3-6 membered cycloalkyl or heterocycloalkyl ring;
• each R4 is independently -L1-L2-L3;
• each R9 is independently H, —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spirocycloalkyl, spiroheterocycloalkyl, spirocycloalkenyl, spiroheterocycloalkenyl, —C(O)Rb, —C(O)ORb, —C(O)NRcRd, —S(O)Rb, —S(O)2NRcRd, —S(O)(═NRb)Rb, —SF5, —P(O)RbRb, —P(O)(ORb)(ORb), —B(ORc)(ORd) or —S(O)2Rb;
• wherein each of —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spirocycloalkyl, spiroheterocycloalkyl, spirocycloalkenyl, spiroheterocycloalkenyl can be optionally substituted by 1-6 Rf groups;
• each L1 is independently absent, or is independently —(CRcRd)p—, —(CRaRc)pO—, —S(O)—, —S(O)2—, —C(═O)—, —C(═O)O—, —C(═O)NRa—, —S(═O)NRa—, —S(═O)2NRa—, or aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;
• each L2 is independently absent, or is independently aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;
• each L3 is independently absent, or is independently H, D, halogen, —OH, —CN, —NO2, —C1-C6alkyl, C1-C8 alkoxide, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, —ORa, —SRa, —NRcRd, —NRaRc, —C(O)Rb, —OC(O)Rb, —C(O)ORb, —C(O)NRcRd, —S(O)Rb, —S(O)2NRcRd, —S(O)(═NRb)Rb, —SF5, —P(O)RbRb, —P(O)(ORb)(ORb), —B(ORc)(ORd) or —S(O)2Rb;
• p is 1, 2, 3 or 4;
• each X1, X2, X3, X4, and X6 is independently N or CR10;
• each R10 is independently H, D, halogen, —OH, —CN, —NO2, —C1-C6alkyl, C1-C8 alkoxide, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, —ORa, —SRa, —NRcRd, —C(O)Rb, —OC(O)Rb, —C(O)ORb, —C(O)NRcRd, —S(O)Rb, —S(O)2NRcRd, —S(O)(═NRb)Rb, —SF5, —P(O)RbRb, —P(O)(ORb)(ORb), —B(ORc)(ORd) or —S(O)2Rb;
• R1 is H, D, —C1-C6alkyl, —C1-C6haloalkyl, C1-C8 alkoxide, —C2-C6alkenyl, —C2-C6alkynyl, —NHR5;
• R5 is H, —C1-C6alkyl, C1-C8 alkoxide, —C2-C6alkenyl, —C2-C6alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;
• R6 is H, D, —OH, —C1-C6alkyl, C1-C8 alkoxide, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spirocycloalkyl, spiroheterocycloalkyl or spiroheterocycloalkenyl;
• R7 is H, —C1-C6alkyl, —C1-C6haloalkyl, —C2-C6alkenyl, or cycloalkyl;
• each Ra is independently H, —C1-C10alkyl, —C2-C10 alkenyl, —C2-C10 alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, or heterocycloalkenyl;
• each Rb, is independently H, D, —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycloalkyl, or heterocycloalkenyl;
• each Rc or Rd is independently H, D, —C1-C10 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OC1-C6alkyl, —O-cycloalkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl;
• or Rc and Rd, together with the atom to which they are both attached, form a monocyclic or multicyclic heterocycloalkyl, or a monocyclic or multicyclic heterocyclo-alkenyl group;
• wherein any of the —C1-C6alkyl, C1-C8 alkoxide, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, spirocycloalkyl, spiroheterocycloalkyl and spiroheterocycloalkenyl groups in any of R1-R10 and L1-L3 is optionally substituted by 1-6 Rf groups;
• and
• each Rf is independently H, D, oxo, halogen, C1-C8 alkoxy, C1-C8 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, —OH, —CN, —NO2, —C2-6 alkenyl, —C2-6 alkynyl, C6-10 aryl, C5-12 heteroaryl, C3-8 cycloalkyl, C3-8 cycloalkenyl, C3-8 heterocycloalkyl, C3-8 heterocycloalkenyl, —ORa, —SRa, —NRcRd, —NRaRc, —C(O)Rb, —OC(O)Rb, —C(O)ORb, —C(O)NRcRd, —S(O)Rb, —S(O)2NRcRd, —S(O)(═NRb)Rb, —SF5, —P(O)RbRb, —P(O)RcRd, —P(O)(ORb)(ORb), —B(ORc)(ORd), —S(O)2Rb, —C(O)NRbORb, —S(O)2ORb, —OS(O)2ORb, or —OPO(ORb)(ORb);
• wherein said C1-C8 alkyl is optionally substituted by 1-6 groups selected from D, halogen, —OH, —CN, —ORa, —SRa, —NRaRd or NRcRd.