US 2023/0146483 A1 · 5-AMINO-8-(4-PYRIDYL)-[1,2,4]TRIAZOLO[4,3-C]PYRIMIDIN-3-ONE COMPOUNDS FOR USE AGAINST CANCER

Abstract

Described herein are triazalone compounds of Formula (I): and pharmaceutically acceptable salts thereof. Methods of making and using compounds of Formula (I) are also described. Compounds of Formula (I) and pharmaceutically acceptable salts thereof can be useful as adenosine receptor antagonists, for example in the treatment of diseases or conditions mediated by the adenosine receptor, such as cancer, movement disorders, or attention disorders.

A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
ring A is:
each R1 and each R2, independently, is halo, C1-3alkyl, —O—C1-3alkyl, —CO2Ra, or —NR7R8;
wherein alkyl is optionally substituted with one or more substituents independently selected from —ORa and halo;
R3 is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, aryl, heterocyclyl, heteroaryl, halo, —ORa, —NRaRb, —CO2Ra, —CONRaRb, —NRaC(O)—Ra, or —NHC(O)—ORa;
wherein heterocyclyl and heteroaryl, independently, include from 1 to 4 heteroatoms independently selected from N, O, and S(O)k;
and
wherein R3 is optionally substituted with from one to three substituents selected from halo, cyano, —Ra, and —ORa;
R4 is absent or —(CHRc)i—(NRa)j—R5;
R5 is:
(1) C3-8cycloalkyl, aryl, 3-, 4-, 6-, or 7-membered heterocyclyl, or 3-, 4-, 6-, or 7-membered heteroaryl;
wherein heterocyclyl and heteroaryl, independently, include from 1 to 4 heteroatoms independently selected from N, O, and S(O)k;
and
wherein one or two ring atoms of R5 is optionally replaced by —C(═O)—;
(2) a multicyclic, 6- to 11-membered, cycloalkyl, aryl, heterocyclyl, or heteroaryl ring system;
wherein heterocyclyl and heteroaryl, independently, include from 1 to 4 heteroatoms independently selected from N, O, and S(O)k;
and
wherein one or two ring atoms of R5 is optionally replaced by —C(═O)—;
or
(3) C1-6alkyl, —ORa, —NRaRb, cyano, —OS(O)2—C1-3alkyl, —CO2Ra, —C(O)NRaRb, —NRa—C(O)—ORa, or —O—C(O)—NRaRb;
and
wherein R5 is optionally substituted with from one to four groups —X—R6;
each X, independently, is a bond, —O—, —NRa—, —S(O)k—, —(CH2)m—, or —C(O)—;
each R6, independently, is H, halo, —ORa, C1-6alkyl, C3-8cycloalkyl, heterocyclyl, heteroaryl, aryl, —CO2Ra, —C(O)NRaRb, —(CH2)n—NRaRb, or cyano;
wherein heterocyclyl and heteroaryl, independently, include from 1 to 4 heteroatoms independently selected from N, O, and S(O)k;
wherein one or two ring atoms of each C3-8cycloalkyl, heterocyclyl, heteroaryl, or aryl, independently, is optionally replaced by —C(═O)—;
wherein each of alkyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl is optionally substituted with one or more substituents independently selected from —Ra, —ORa, —(CH2)n—NRaRb, and halo;
each R7 and each R8, independently, is Ra;
or R7 and R8 together with the atom to which they are attached form a 3- to 8-membered heterocyclyl optionally substituted with one or more substituents independently selected from —ORa and halo;
each Ra and each Rb, independently, is H, C1-6alkyl, C3-8cycloalkyl, or C4-9cycloalkylalkyl;
wherein each Ra and each Rb, independently, is optionally substituted with one or more substituents independently selected from —OH and halo;
each Rc, independently, is H, halo, C1-3alkyl, or —(CH2)n—NRaRb;
wherein alkyl is optionally substituted with one or more substituents independently selected from —ORa and halo;
a is 0 or 1;
i is 0, 1, 2, or 3;
j is 0 or 1;
each k, independently, is 0, 1, or 2;
each m, independently, is 1 or 2;
and
each n, independently, is 0 or 1.

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5-amino-8-(4-pyridyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one compounds for use against cancer

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5-amino-8-(4-pyridyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3-one compounds for use against cancer

Life of this patent

Abstract

Claims15