US 11,685,744 B2
CDK inhibitors and their use as pharmaceuticals
Andrew W. Buesking, Wilmington, DE (US); Andrew Paul Combs, Kennett Square, PA (US); Jincong Zhuo, Garnet Valley, PA (US); Ryan Holmes, Wilmington, DE (US); Sarah Pawley, Landenberg, PA (US); and Xiaowei Wu, Wilmington, DE (US)
Assigned to Prelude Therapeutics Incorporated, Wilmington, DE (US)
Filed by Prelude Therapeutics, Incorporated, Wilmington, DE (US)
Filed on Sep. 21, 2021, as Appl. No. 17/480,323.
Claims priority of provisional application 63/221,959, filed on Jul. 15, 2021.
Claims priority of provisional application 63/081,126, filed on Sep. 21, 2020.
Prior Publication US 2022/0089608 A1, Mar. 24, 2022
Int. Cl. A61K 31/4188 (2006.01); A61K 31/4196 (2006.01); A61K 31/506 (2006.01); A61K 31/5355 (2006.01); A61K 31/551 (2006.01); A61K 31/565 (2006.01); A61P 35/00 (2006.01); C07D 495/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 495/04 (2013.01) [A61K 31/4188 (2013.01); A61K 31/4196 (2013.01); A61K 31/506 (2013.01); A61K 31/5355 (2013.01); A61K 31/551 (2013.01); A61K 31/565 (2013.01); A61P 35/00 (2018.01); C07D 519/00 (2013.01)] 54 Claims
 
1. A compound of Formula (I)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or solvate or N-oxide thereof, wherein
ring A is a 5-7-membered heteroaryl;
V=CL1R1 or N
n is 1 or 2 or 3;
m is 1 or 2;
o is 1, 2, 3, 4, or 5;
each L1 is independently a bond, O, NR or C1-C6 alkylene, wherein R is H or C1-C6alkyl;
each R1 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;
each R2 is independently H, D, halogen, C1-C8 alkoxide C1-C8 alkyl, haloalkyl, or CN and
each R3 is independently H, D, halogen, oxo, —OH, —CN, —NO2, —C1-C6alkyl, —C2-C6alkenyl, —C2-C6alkynyl, C0-C1alk-aryl, C0-C1alk-heteroaryl, cycloalkyl, cycloalkenyl, heterocycloalkyl, or heterocycloalkenyl, —ORa, —ORb, —SRb, —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(ORd)(ORc) or —S(O)2Rb;
each Ra is independently H, D, —C(O)Rb, —C(O)ORc, —C(O)NRcRd, —C(═NRb)NRbRc, —C(═NORb)NRbRc, —C(═NCN)NRbRc, —P(ORc)2, —P(O)RcRb, —P(O)ORcRb, —S(O)Rb, —S(O)NRcRd, —S(O)2Rb, —S(O)2NRcRd, SiRb3, —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;
each R4 is independently H, D, halogen, C1-C8 alkoxide or C1-C8 alkyl, haloalkyl or CN.