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1. A compound of Formula (I): or a pharmaceutically acceptable salt, pro-drug, biologically active metabolite, isomer, or stereoisomer thereof, wherein:
Ring A′ is a heteroaryl ring or an unsaturated or partially unsaturated heterocyclic ring, wherein:
G is S, O, CR1, C(R1)2, N, or NR1;J is C, CR1, C(R1)2, O, N, or NR1; and,L is C, CR1, C(R1)2, N, or NR1;provided that J is not O if G is O or S; and,Ring A is an optionally substituted pyrazine, optionally substituted pyridine, or optionally substituted phenyl;Ring B is a seven-membered ring optionally substituted with deuterium, wherein:
X is —C(R5)2—, —C(R5)═, —C(═O)—, —N(Ra)—, —O—, —S—, —S(O)—, or —S(O)2—; orwhen X is —C(R5)2—, both R5 substituents, together with the carbon atom to which they are attached, optionally forms a cyclopropyl ring spiro to Ring B;Y is —C(R5)2C(R5)2—, ═C(R5)C(R5)2—, —C(R5)2C(R5)═, ═C(R5)C(R5)═, —N(Ra)C(R5)2—, —C(R5)2N(Ra)—, —C(═O)C(R5)2—, —C(R5)2C(═O)—, —O—C(═O)—, —C(═O)—O—, —OC(R5)2—, or —C(R5)2—O—;
provided that X—Y does not form —N(Ra)—C(R5)2—N(Ra)—, —S—C(R5)2—N(Ra)—, —S—C(R5)2—O—, —O—C(R5)2—N(Ra)—, —C(═O)—C(═O)—C(R5)2—, —C(═O)—C(═O)—O—, —N(Ra)—C(R5)2—O—, —O—C(R5)2—O—, —S—C(═O)C(R5)2—, —S—C(═O)—O—, or —S—C(R5)2—O— bonds; andprovided that X—Y does not result in an oxygen atom adjacent to either a nitrogen atom, a sulfur atom or another oxygen atom; andprovided that X—Y does not result in two nitrogen atoms adjacent to one another;Ring C is an optionally substituted, saturated or partially unsaturated, five- or six-membered carbocyclyl or heterocyclyl ring;R1 is independently H, deuterium, —Br, —Cl, —F, —CF3, —CN, —ORb, -optionally substituted (C1-C3)alkylene-Rb, optionally substituted (C1-C3)alkyl, optionally substituted aryl, optionally substituted (C3-C6)cycloalkyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, —S(O)2Rb—, ═O, or —N(Ra)(Rb);R1a is independently H, deuterium, —Br, —Cl, —F, —CF3, —CN, optionally substituted (C1-C6)alkyl, optionally substituted (C3-C6)cycloalkyl, optionally substituted heterocyclyl, —S(O)2—Ra, or —N(Ra)2;R2 is —CD3, —CH2CD3, —CN, -allyl, —CH2NHC(═O)(C1-C3)alkyl, —CH2NHSO2(C1-C3)alkyl, —N(R)—SO2-optionally substituted alkyl; —N(R)(Rg), —N(R)-optionally substituted cycloalkyl, —N(R)-optionally substituted aryl, —N(R)-optionally substituted heteroaryl, —N(R)-optionally substituted heterocyclyl, —N(R)C(O)-optionally substituted alkyl, —N(R)2, —C(O)N(Ra)2, —CH2-optionally substituted aryl, —CH2-optionally substituted (C3-C6)cycloalkyl, optionally substituted (C1-C3)alkyl, optionally substituted (C2-C3)alkenyl, —CH2-optionally substituted heteroaryl, —(CH2)n1-optionally substituted heterocyclyl, —C(Rd)2—Re, or —C(═O)—Re, provided that when R2 is —C(Rd)2—Re, only one Rd can be OH;R3 is independently a bond, deuterium, —CD3, —CF3, —N(Ra)SO2Rc, —N(Ra)CORc, —CON(Ra)Rc, —N(Ra)COORc, —N(Ra)2, —O—C(O)NR-optionally substituted alkyl, optionally substituted (C2-C6)alkynyl, ═O, —ORa, —ORf, optionally substituted (C1-C4)alkyl, optionally substituted (C1-C4)alkyl-O—(C1-C4)alkyl, —(C(Ra)2)r-optionally substituted (C3-C6)cycloalkyl, —(C(Ra)2)r-optionally substituted aryl, —(C(Ra)2)r-optionally substituted heteroaryl, —(C(Ra)2)r—N(Ra)-optionally substituted heteroaryl, —(C(Ra)2)r—N(Ra)—(C(Ra)2)r-optionally substituted aryl, or a carbocyclic or heterocyclic spirocyclic moiety attached to ring C;R4 is a bond, H, deuterium, —CD3, —F, optionally substituted (C1-C3)alkyl, —OH or —O-optionally substituted (C1-C3)alkyl;R5 is independently H, deuterium, —CD3, —F, —CF3, —N(Ra), —ORa, or optionally substituted (C1-C3)alkyl; and,Ra is independently H, deuterium, optionally substituted (C3-C6)cycloalkyl, or optionally substituted (C1-C3)alkyl;Rb is H, optionally substituted (C1-C3)alkyl, optionally substituted aryl, optionally substituted (C3-C6)cycloalkyl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;Rc is optionally substituted (C1-C3)alkyl or optionally substituted aryl;Rd is independently H, deuterium, —OH, or optionally substituted (C1-C6) alkyl;Re is —CF3, optionally substituted aryl, optionally substituted (C1-C6)alkyl, optionally substituted (C3-C6)cycloalkyl, optionally substituted heteroaryl, or optionally substituted heterocyclyl;Rf is —H, —SO2NH2, —CH2CO2H, —CH2CONH2, —P(═O)(OH)(OH), —C(O)-optionally substituted(C1-C6) alkyl, —C(O)N(optionally substituted (C1-C6)alkyl)2, —C(O)(optionally substituted (C1-C6)alkyl)2, —C(O)-optionally substituted aryl, —C(O)-optionally substituted heterocyclyl, —C(O)-optionally substituted (C3-C6)cycloalkyl, —C(O)—CR2-optionally substituted heterocyclyl or C(O)—CR2-optionally substituted heteroarylRg is —CH2-optionally substituted (C3-C6)cycloalkyl, —CH2-optionally substituted heteroaryl, or —CH2-optionally substituted heterocyclyl;R is independently H or (C1-C3)alkyl;m is 0, 1, or 2;n1 is independently 0 or 1;p is 1, 2, 3 or 4; andr is independently 0, 1 or 2.
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