US 12,403,144 B2
HECT E3 ligase inhibitors and uses thereof
Sebastiano Pasqualato, Milan (IT); Maurizio Pasi, Torre d'Isola (IT); Raffaella Amici, Codogno (IT); Mario Varasi, Milan (IT); Ciro Mercurio, Legnano (IT); Luca Sartori, Milan (IT); Simona Polo, Milan (IT); Elena Maspero, Milan (IT); and Giovanni Faga', Milan (IT)
Assigned to IFOM —FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE, Milan (IT); and IEO—ISTITUTO EUROPEO DI ONCOLOGIA S.R.L., Milan (IT)
Appl. No. 17/616,070
Filed by IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE, Milan (IT); and IEO—ISTITUTO EUROPEO DI ONCOLOGIA S.R.L., Milan (IT)
PCT Filed Jun. 3, 2020, PCT No. PCT/EP2020/065372
§ 371(c)(1), (2) Date Dec. 2, 2021,
PCT Pub. No. WO2020/245213, PCT Pub. Date Dec. 10, 2020.
Claims priority of application No. 19177953 (EP), filed on Jun. 3, 2019.
Prior Publication US 2022/0339163 A1, Oct. 27, 2022
Int. Cl. A61K 31/5517 (2006.01); A61K 31/55 (2006.01); A61K 31/5513 (2006.01); A61K 31/553 (2006.01); A61P 35/00 (2006.01); C07D 223/28 (2006.01); C07D 243/38 (2006.01); C07D 267/20 (2006.01); C07D 487/04 (2006.01); C07D 495/04 (2006.01)
CPC A61K 31/5517 (2013.01) [A61K 31/55 (2013.01); A61K 31/5513 (2013.01); A61K 31/553 (2013.01); A61P 35/00 (2018.01); C07D 223/28 (2013.01); C07D 243/38 (2013.01); C07D 267/20 (2013.01); C07D 487/04 (2013.01); C07D 495/04 (2013.01)] 19 Claims
 
1. A compound of general formula (I):

OG Complex Work Unit Chemistry
wherein:
Z is CH2 or CO;
R1 is hydrogen or C1-C6 alkyl;
R2 is COOR4, CO—R5, CN or CONR6R7;
R3 is H or OH;
n is an integer from 1 to 3;
m is 1 or 2;
W is aryl or heteroaryl;
A-B is CH2—CH2, O—CH2, CH2—O, NR8-CO or CO—NR8;
X, X′, Y are each independently selected from the group consisting of: hydrogen, C1-C6 alkyl, OH, NH2, C1-C6-alkoxy, C1-C6-alkylamino, C1-C6-dialkylamino, CONR6R7, halogen, CF3, NO2 and CN, said C1-C6 alkyl or C1-C6 alkoxy being optionally substituted with a substituent selected from the group consisting of: R9, OH, NH2, C1-C6-alkoxy, (C1-C6-alkoxy)C1-C6-alkoxy, C2-C6-alkynyloxy, C2-C6-alkynyl, C1-C6-alkylamino, C1-C6-dialkylamino, aryl and heteroaryl;
R4 is hydrogen or C1-C6 alkyl, said C1-C6 alkyl being optionally substituted with a substituent selected from the group consisting of: R9, C2-C6-alkynyl, C1-C6-alkoxy, C2-C6-alkynyloxy and (C1-C6-alkoxy)C1-C6-alkoxy;
R5 is C3-6 cycloalkyl, C1-C6 alkyl, aryl, heteroaryl,

OG Complex Work Unit Chemistry
 said C1-C6 alkyl being optionally substituted by aryl or heteroaryl;
R6, R7 are each independently selected from the group consisting of: hydrogen, aryl, C1-C6 alkyl, C1-C6-alkoxy, O-aryl and O-heterocycloalkyl, said C1-C6 alkyl, C1-C6-alkoxy, O-aryl or O-heterocycloalkyl being optionally substituted with a substituent selected from the group consisting of: OH, NH2, C1-C6-alkoxy, C1-C6-alkylamino, C1-C6-dialkylamino, aryl, heteroaryl and C2-C6-alkynyl;
R8 is hydrogen or C1-C6 alkyl, said C1-C6 alkyl being optionally substituted with a substituent selected from the group consisting of: OH, NH2, C1-C6-alkoxy, C1-C6-alkylamino, C1-C6-dialkylamino, aryl, heteroaryl, (C1-C6-alkoxy)C1-C6-alkoxy, [(C1-C6-alkoxy)C1-C6-alkoxy]C1-C6-alkoxy and C2-C6-alkynyloxy;
R9 is k or

OG Complex Work Unit Chemistry
k is an integer from 1 to 10;
or a stereoisomer, solvate, tautomer or pharmaceutically acceptable salt thereof.