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US 12,741,976 B2Granted
Quinoxaline derivatives and uses thereof
AssigneeBlack Diamond Therapeutics, Inc.
InventorsMatthew C. Lucas, Fernando Padilla
Life of this patent
Estimating the term…
Abstract
The present disclosure relates compounds of Formula (I′): and pharmaceutically acceptable salts and stereoisomers thereof. The present disclosure also relates to methods of preparing the compounds, compositions comprising the compounds, and methods of using the compounds, e.g., in the treatment of cancer.
Claims23
A compound of Formula (I′):
- or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
- each independently represents a single bond or a double bond;
- n is 0 or 1;
- W1 is C(RW1) when connected to one double bond and one single bond, N(RW1) when connected to two single bonds, or N when connected to one double bond and one single bond;
- RW1 is H, C1-C6 alkyl, or —S(═O)2—(C1-C6 alkyl);
- W2 is C(RW2) when connected to one double bond and one single bond, N(RW2) or O when connected to two single bonds, or N when connected to one double bond and one single bond;
- RW2 is H, C1-C6 alkyl, or —S(═O)2—(C1-C6 alkyl);
- W3 is C or N;
- W4 is C(RW4) or N;
- RW4 is H, halogen, cyano, C1-C6 alkyl, or —S(═O)2—(C1-C6 alkyl);
- W5 is C(RW5) or N;
- RW5 is H, halogen, cyano, C1-C6 alkyl, or —S(═O)2—(C1-C6 alkyl);
- W6 is C(RW6) when connected to one double bond and one single bond, N(RW6) when connected to two single bonds, or N when connected to one double bond and one single bond;
- RW6 is H, halogen, cyano, C1-C6 alkyl, C1-C6 alkoxyl, C1-C6 haloalkyl, or —S(═O)2—(C1-C6 alkyl);
- X1 is C or N;
- X2 is N, O, or C(RX2);
- RX2 is H or C1-C6 alkyl;
- X3 is N, O, or C(RX3);
- RX3 is H or C1-C6 alkyl;
- R3 is H, halogen, cyano, NH2, —NH(C1-C6 alkyl), —NHC(═O)(C1-C6 haloalkyl), —NHC(•)O(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)H, —C(═O)(C1-C6 alkyl), —C(═O)O(C1-C6 alkyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1- C6 alkoxy, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, 3- to 12-membered heterocycloalkyl, 3- to 12-membered heterocycloalkenyl, C6-C10 aryl, or 5- to 10-membered heteroaryl, wherein the —NH(C1-C6 alkyl), —NHC(═O)(C1-C6 haloalkyl), —NHC(═O)O(C1-C6 alkyl), N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)(C1-C6 alkyl), —C(═O)O(C1-C6 alkyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, 3- to 12-membered heterocycloalkyl, 3- to 12-membered heterocycloalkenyl, C6-C10 aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more R3a;
- each R3a independently is halogen, cyano, oxo, —OH, NH2, —NH(C1-C6 alkyl), —NHC(═O)O(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)(C1-C6 alkyl), —C(═O)O(C1-C6 alkyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C6-C10 aryl, or 5- to 10-membered heteroaryl, wherein the —NHC(═O)O(C1-C6 alkyl) is optionally substituted with one or more halogen;
- R5 is H, halogen, cyano, or C1-C6 alkyl;
- R6 is H, halogen, cyano, or C1-C6 alkyl;
- Y is absent, C1-C6 alkyl, C2-C6 alkenyl, or C1-C6 alkoxyl, wherein the C1-C6 alkyl, C2-C6 alkenyl, or C1-C6 alkoxyl is optionally substituted with one or more halogen, oxo, cyano, —OH, —NH2, —NH(C1-C6 alkyl)-OH, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxyl optionally substituted with —(C1-C6 alkyl) (C6-C10 aryl), or C3-C12 cycloalkyl;
- Z is absent, H, C3-C12 cycloalkyl, C3-C12 cycloalkenyl, 3- to 12-membered heterocycloalkyl, 3- to 12-membered heterocycloalkenyl, C6-C10 aryl, or 5- to 10-membered heteroaryl, wherein the C3-C12 cycloalkyl, C3-C12 cycloalkenyl, 3- to 12-membered heterocycloalkyl, 3- to 12-membered heterocycloalkenyl, C6-C10 aryl, or 5- to 10-membered heteroaryl is optionally substituted with one or more RZ;
- each RZ independently is oxo, halogen, cyano, —OH, =NRZa, —NH2, —NHRZa, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(C1-C6 alkyl), —S(═O)(═NRZa)—(C1-C6 alkyl), —S(═O)2—(C1-C6 alkyl), —S(═O)2—(C2-C6 alkenyl), —C(═O) (3- to 12-membered heterocycloalkyl), —C(═O)NH(C1-C6 alkyl), —C(═O)NRZa, —C(═O)—(C1-C6 alkyl), —C(═O)—(C2-C6 alkenyl), —C(═O)—(C1-C6 alkoxyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxyl, C3-C12 cycloalkyl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the —NH(C1-C6 alkyl), N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)—(C1-C6 alkyl), —C(═O)—(C2-C6 alkenyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxyl, C3-C12 cycloalkyl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more RZa,
- each RZa independently is H, oxo, halogen, cyano, —OH, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)—(C1-C6 alkyl), —C(═O)—(C2-C6 alkenyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxyl, C3-C12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the NH(C1-C6 alkyl), N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)—(C1-C6 alkyl), —C(═O)—(C2-C6 alkenyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxyl, C3-C12 cycloalkyl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more RZb;
- and
- each RZb independently is oxo, halogen, cyano, —OH, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)—(C1-C6 alkyl), —C(═O)—(C2-C6 alkenyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 alkoxyl.
26 more elements
A compound of Formula (I):
- or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
- each independently represents a single bond or a double bond;
- n is 0 or 1;
- W1 is C(RW1) when connected to one double bond and one single bond, N(RW1) when connected to two single bonds, or N when connected to one double bond and one single bond;
- RW1 is H, C1-C6 alkyl, or —S(═O)2—(C1-C6 alkyl);
- W2 is C(RW2) when connected to one double bond and one single bond, N(RW2) when connected to two single bonds, or N when connected to one double bond and one single bond;
- RW2 is H, C1-C6 alkyl, or —S(═O)2—(C1-C6 alkyl);
- W3 is C or N;
- X1 is C or N;
- X2 is N, O, or C(RX2);
- RX2 is H or C1-C6 alkyl;
- X3 is N, O, or C(RX3);
- RX3 is H or C1-C6 alkyl;
- R1 is H, halogen, cyano, or C1-C6 alkyl;
- R2 is H, halogen, cyano, or C1-C6 alkyl;
- R3 is H, halogen, cyano, or C1-C6 alkyl;
- R4 is H, halogen, cyano, or C1-C6 alkyl;
- Y is absent or C1-C6 alkyl optionally substituted with one or more oxo or —OH;
- Z is H, C3-C8 cycloalkyl, or 3- to 8-membered heterocycloalkyl, wherein the C3-C8 cycloalkyl or 3- to 8-membered heterocycloalkyl is optionally substituted with one or more R2;
- each RZ independently is oxo, halogen, cyano, —OH, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)—(C1-C6 alkyl), —C(═O)—(C2-C6 alkenyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxyl, C3-C8 cycloalkyl, or 3- to 8-membered heterocycloalkyl, wherein the —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)—(C1-C6 alkyl), —C(═O)—(C2-C6 alkenyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxyl, C3-C8 cycloalkyl, or 3- to 8-membered heterocycloalkyl is optionally substituted with one or more RZa,
- each RZa independently is oxo, halogen, cyano, —OH, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)—(C1-C6 alkyl), —C(═O)—(C2-C6 alkenyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxyl, C3-C8 cycloalkyl, or 3- to 8-membered heterocycloalkyl, wherein the —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)—(C1-C6 alkyl), —C(═O)—(C2-C6 alkenyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxyl, C3-C8 cycloalkyl, or 3- to 8-membered heterocycloalkyl is optionally substituted with one or more RZb;
- and
- each RZb independently is oxo, halogen, cyano, —OH, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —S(═O)2—(C1-C6 alkyl), —C(═O)—(C1-C6 alkyl), —C(═O)—(C2-C6 alkenyl), C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 alkoxyl.
20 more elements
A compound selected from;
- or a pharmecutically acceptable salt or stereoisomer thereof.
Dependencies are inferred from the claim text.