N-(5-SUBSTITUTED-[(1,3,4-THIADIAZOLYL) OR (THIAZOLYL)])(SUBSTITUT ED)CARBOXAMIDE COMPOUNDS AND USE THEREOF FOR INHIBITING HUMAN POLYMERASE THETA

• Main Authors: SOW Boubacar, PERRYMAN Alexander, BUBENIK Monica, DIETRICH Evelyne, MOCHIRIAN Philippe, BENDAHAN David, LIU Bingcan, GALLANT Michel, SURPRENANT Simon, SZYCHOWSKI Janek
• Format: Patent
• Language: English; Spanish
• Published: 03.06.2024
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Disclosed are compounds of formula (I), wherein V is N or CR; W is optionally substituted alkylene, alkenylene, alkynylene, cycloalkylene, or arylene; X is optionally substituted heterocyclylene, heteroarylene, arylene, wherein X may be substituted with -L1- Rx, wherein L1 is -O-, - NRX1-, optionally substituted heterocyclylene, heteroarylene, or cycloalkylene, Rx is optionally substituted alkyl, heteroalkyl, heterocyclyl, heteroaryl, cycloalkyl C1-6 alkyl, or heteroaryl C1-6alkyl, and RX1 is hydrogen or optionally substituted alkyl; Y is optionally substituted heterocyclyl, heteroaryl, or aryl; Z is a H, optionally substituted alkyl, alkynyl, alkoxy, cycloalkyl, heterocyclyl, heteroaryl, or aryl; and R is hydrogen, halogen, optionally substituted alkyl, CN, cycloalkyl, alkoxy, cycloalkoxy, N(R1)2, or C(O)NHz, wherein each R1 is hydrogen alkyl, or cycloalkyl. The compounds of formula (I) are useful for inhibiting human Polymerase Theta (Polθ) and for treating cancers, such as carcinoma, sarcoma, adenocarcinoma, leukemia, lymphoma, and melanoma. Se describen compuestos de la fórmula (I), en donde V es N o CR; W es alquileno opcionalmente sustituido, alquenileno, alquinileno, cicloalquileno o arileno; X es heterociclileno opcionalmente sustituido, heteroarileno, arileno, en donde X puede estar sustituido con -L1-Rx, en donde L1 es -O-NRX1-, heterociclileno opcionalmente sustituido, heteroarileno o cicloalquileno, Rx es alquilo opcionalmente sustituido, heteroalquilo, heterociclilo, heteroarilo, cicloalquilo C1-6 alquilo o heteroarilo C1-6 alquilo , y Rx1 es hidrógeno o alquilo opcionalmente sustituido; Y es heterociclilo opcionalmente sustituido, heteroarilo o arilo; Z es un H, alquilo opcionalmente sustituido, alquinilo, alcoxi, cicloalquilo, heterociclilo, heteroarilo o arilo; y R es hidrógeno, halógeno, alquilo opcionalmente sustituido, CN, cicloalquilo, alcoxi, cicloalcoxi, N(R1)2 o C(O)NHz, en donde cada R1 es hidrógeno, alquilo o cicloalquilo. Los compuestos de la fórmula (I) son útiles para inhibir la Polimerasa Theta (Pol?) humana y para tratar cánceres, como carcinoma, sarcoma, adenocarcinoma, leucemia, linfoma y melanoma.