CPC C07D 495/14 (2013.01) [A61K 45/06 (2013.01); A61P 15/08 (2018.01); A61P 35/00 (2018.01); C07D 498/14 (2013.01); C07B 2200/05 (2013.01)] | 24 Claims |
1. A compound of Formula I:
or a pharmaceutically acceptable salt or solvate or N-oxide thereof, wherein
ring A is a 4-9-membered cycloalkyl or heterocycloalkyl ring;
ring B is a 5-membered heteroaryl selected from:
Z is O, S, NRb, NORb or N—CN,
m is 0, 1 or 2;
n is 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9;
s is 0, 1, 2 or 3;
t is 0, 1, 2 or 3;
q is 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9;
each R1, when present, is independently H, D, halogen, —OH, —CN, —NO2, oxo, —C1-C6alkyl, C1-6alkoxide, —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)(═NR)Rb, —SF5, —P(O)RbRb, —P(O)(ORb)(ORb), —B(ORc)(ORd) or —S(O)2Rb;
or two R1 together with the carbon atom(s) to which they are both attached at same carbon or different carbons, form a carbocyclic or heterocyclic group;
each R2 is independently H, D, halogen, C1-C8 alkoxide, C1-C8 alkyl, haloalkoxide, SF5, or CN, wherein the C1-8alkyl may be optionally substituted with D, halogen, —OH, —CN, or cycloalkyl;
each R4 is independently H, D, halogen, CN, —C2-C6alkenyl, —C2-C6alkynyl, C1-C8 alkoxide, C1-C8 alkyl, haloalkyl, C1-C8 hydroxylalkyl, or C3-C8 cycloalkyl or C3-C8 heteroycloalkyl;
each Ra is independently H, D, —C(O)Rb, —C(O)ORc, —C(O)NRcRd, —C(═NR)NRbRc, —C(═NORb)NRbRc, —C(═NCN)NRbRc, —P(ORc)2, —P(O)ORcRb, —S(O)2Rb, —S(O)2NRcRd, SiR3, —C1-C10alkyl, —C2-C10 alkenyl, —C2-C10 alkynyl, C0-C1alk-aryl, cycloalkyl, cycloalkenyl, C0-C1alk-heteroaryl, heterocycloalkyl, or heterocycloalkenyl;
each Rb, is independently H, D, —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, C0-C1alk-aryl, cycloalkyl, cycloalkenyl, C0-C1alk-heteroaryl, heterocycloalkyl, or heterocycloalkenyl;
each Rc is independently H, D, —C1-C10 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OC1-C6alkyl, —O-cycloalkyl, aryl, C1alk-aryl, heteroaryl, cycloalkyl, cycloalkenyl, C1alk-heteroaryl, heterocycloalkyl, or heterocycloalkenyl;
each Rd is independently H, D, —C1-C10 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OC1-C6alkyl, —O-cycloalkyl, aryl, C1alk-aryl, heteroaryl, cycloalkyl, cycloalkenyl, C1alk-heteroaryl, heterocycloalkyl, or heterocycloalkenyl;
or Rc and Rd, together with the atoms to which they are both attached, form a monocyclic or multicyclic heterocycloalkyl, or a monocyclic or multicyclic heterocyclo-alkenyl group;
R5 is H, ORb, C1-4alkyl, wherein the C1-4alkyl may be optionally substituted with at least one of D, halogen, —OH, —CN or an amine, cycloalkyl, heterocycloalkyl; and
each R6, when present, 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)OR, —C(O)NRcRd, —S(O)Rb, —S(O)2NRcRd, —S(O)(═NR)Rb, —SF5, —P(O)RaRb, —P(O)(ORb)(ORb), —B(ORc)(ORd) or —S(O)2Rb; wherein said that —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl is optionally substituted by 1-6 R groups selected from H, D, halogen, —OH, —CN, —ORa, —SRa, —NRcRd, —NRaRc, —C(O)Rb, —OC(O)Rb, —C(O)OR, —C(O)NRcRd, —S(O)Rb, —S(O)2NRcRd, —S(O)(═NR)Rb, —SF5, —P(O)RbRb, —P(O)(ORb)(ORb), —B(ORc)(ORd) or —S(O)2Rb;
or two R6 groups together with the atom(s) to which they attached (same atom or different atoms) can form a spirocyclic group, multicyclic heterocycloalkyl, or a multicyclic cycloalkyl group;
X is O or NR5; and
R10 is H, D, —NRcRd, —NRaRc, C1-6alkyl, C3-7cycloalkyl, C4-7heterocycloalkyl, C3-7cycloalkylalkyl, C4-7heterocycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, or haloalkyl; wherein said that C1-6alkyl, C3-7cycloalkyl, C4-7heterocycloalkyl, C3-7cycloalkylalkyl, C4-7heterocycloalkylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted by 1-6 R selected from H, D, halogen, —OH, —CN, —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.
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