US 12,486,290 B2
Isoindolinone and indazole compounds for the degradation of EGFR
Christopher G. Nasveschuk, Stoneham, MA (US); Martin Duplessis, Somerville, MA (US); Jae Young Ahn, Somerville, MA (US); Alexander W. Hird, Belmont, MA (US); Ryan E. Michael, Erie, CO (US); Kiel Lazarski, Boston, MA (US); Yanke Liang, Belmont, MA (US); Georg Jaeschke, Basel (CH); Antonio Ricci, Biel-Benken (CH); Annick Goergler, Colmar (FR); and Daniel Rueher, Raedersdorf (FR)
Assigned to C4 THERAPEUTICS, INC., Watertown, MA (US)
Filed by C4 THERAPEUTICS, INC., Watertown, MA (US)
Filed on May 12, 2025, as Appl. No. 19/205,510.
Application 19/205,510 is a continuation of application No. 18/144,800, filed on May 8, 2023.
Application 18/144,800 is a continuation of application No. 17/843,769, filed on Jun. 17, 2022, granted, now 11,673,902, issued on Jun. 13, 2023.
Application 17/843,769 is a continuation of application No. PCT/US2020/066211, filed on Dec. 18, 2020.
Claims priority of provisional application 62/951,464, filed on Dec. 20, 2019.
Claims priority of provisional application 62/951,467, filed on Dec. 20, 2019.
Prior Publication US 2025/0270234 A1, Aug. 28, 2025
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 519/00 (2006.01); A61K 9/00 (2006.01); A61K 9/02 (2006.01); A61K 9/08 (2006.01); A61K 9/20 (2006.01); A61K 9/48 (2006.01); A61K 47/10 (2017.01); A61K 47/12 (2006.01); A61K 47/26 (2006.01); A61K 47/32 (2006.01); A61K 47/38 (2006.01); C07D 487/04 (2006.01)
CPC C07D 519/00 (2013.01) [A61K 9/009 (2013.01); A61K 9/02 (2013.01); A61K 9/08 (2013.01); A61K 9/2013 (2013.01); A61K 9/2018 (2013.01); A61K 9/2054 (2013.01); A61K 9/4825 (2013.01); A61K 9/485 (2013.01); A61K 9/4858 (2013.01); A61K 9/4866 (2013.01); A61K 47/10 (2013.01); A61K 47/12 (2013.01); A61K 47/26 (2013.01); A61K 47/32 (2013.01); A61K 47/38 (2013.01); C07D 487/04 (2013.01)] 30 Claims
 
1. A compound of formula (I)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof;
wherein:
A is

OG Complex Work Unit Chemistry
A1 is selected from the group consisting of —NH— and —O—;
A2 is selected from the group consisting of —N— and —CR52—;
R1 is selected from the group consisting of H, halogen, and C1-6-alkyl;
R52 is selected from the group consisting of H, halogen, cyano, C1-6-alkoxy, halo-C1-6-alkoxy, C1-6-alkyl, halo-C1-6-alkyl, C3-8-cycloalkyl, and halo-C3-8-cycloalkyl;
R2 is selected from the group consisting of H, halogen, C1-6-alkyl, halo-C1-6-alkyl, C3-8-cycloalkyl, and halo-C3-8-cycloalkyl;
R3 is selected from the group consisting of H, halogen, C1-6-alkyl, halo-C1-6-alkyl, C3-8-cycloalkyl, and halo-C3-8-cycloalkyl;
R4 and R5 are H;
or R4 and R5 together form —(CH2)q—;
R6 is selected from the group consisting of H, halogen, cyano, C1-6-alkoxy, halo-C1-6-alkoxy, C1-6-alkyl, halo-C1-6-alkyl, C3-8-cycloalkyl, and halo-C3-8-cycloalkyl;
R7 is selected from the group consisting of H, halogen, cyano, C1-6-alkyl, halo-C1-6-alkyl, C3-8-cycloalkyl, and halo-C3-8-cycloalkyl;
R70 is selected from the group consisting of H, halogen, cyano, C1-6-alkyl, halo-C1-6-alkyl, C3-8-cycloalkyl, and halo-C3-8-cycloalkyl;
L1

OG Complex Work Unit Chemistry
C is absent or selected from the group consisting of ring systems F, G, and H:

OG Complex Work Unit Chemistry
Y1 is selected from the group consisting of —N— and —CH—;
Y2 is selected from the group consisting of —N— and —CR16—;
R12, R13, R14 and R15 are independently selected from the group consisting of H, halogen, and hydroxy-C1-6-alkyl;
R16 is selected from the group consisting of H, hydroxy, and fluoro;
L3 is absent or selected from the group consisting of —(CH2)m—C(O)—, —C(O)—(CH2)p—, —C(O)—C(O)—, —NR10—C(O)—, —C(O)—NR10—, —C(O)O—, —CH2—CF2—CH2—, —CH2—,

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
m is 0, 1 or 2;
p is 0, 1, 2 or 3;
q is 1 or 2;
R10 is selected from the group consisting of H and C1-6-alkyl;
D is selected from the group consisting of ring systems I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, and X, all the ring systems being optionally substituted by one to three substituents selected from R80, R81 and R82:

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
R80, R81 and R82 are independently selected from the group consisting of halogen, cyano, hydroxy, hydroxy-C1-6-alkyl, C1-6-alkoxy, halo-C1-6-alkoxy, C1-6-alkyl, halo-C1-6-alkyl, C3-8-cycloalkyl, and halo-C3-8-cycloalkyl;
L4 is absent or selected from the group consisting of —CH2— and —O—;
E is selected from the group consisting of ring systems Y, Z, AA, AB, and AC:

OG Complex Work Unit Chemistry
L5 is absent or

OG Complex Work Unit Chemistry
 and
B is selected from the ring system AD and AE:

OG Complex Work Unit Chemistry