发明名称 Lactam kinase inhibitors
摘要 Compounds useful as kinase inhibitors are provided herein, as well as salts, pharmaceutical compositions, methods of medical treatment and methods of synthesis thereof.
申请公布号 US9260442(B2) 申请公布日期 2016.02.16
申请号 US201414498796 申请日期 2014.09.26
申请人 G1 Therapeutics, Inc. 发明人 Tavares Francis Xavier
分类号 A61K31/535;C07D487/14;C07D498/14 主分类号 A61K31/535
代理机构 Knowles Intellectual Property Strategies, LLC 代理人 Knowles Intellectual Property Strategies, LLC ;Bellows Brent R.
主权项 1. A compound of formula (Q):wherein R26 is H, C1-C6 alkyl, haloalkyl, cycloalkyl or heterocycloalkyl containing atoms selected from N, O, or S; each R31 is independently aryl, alkyl, cycloalkyl or haloalkyl, wherein each of said alkyl, cycloalkyl and haloalkyl groups optionally substituted with N or O heteroatoms, and two R31s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached optionally form a 3-8-membered cycle; yy is 0, 1, 2, 3 or 4; ZZ is —(CH2)xx— wherein xx is 1, 2, 3, or 4, or —O—(CH2)xx- wherein xx is 2, 3 or 4; R55 is NHRA, wherein RA is unsubstituted C1-C8 alkyl, cycloalkylalkyl, -TT-RR, C1-C8 cycloalkyl or heterocycloalkyl containing atoms selected from N, O, or S, TT is an unsubstituted or substituted C1-C8 alkyl or C3-C8 cycloalkyl linker; and RR is a hydroxyl, unsubstituted or substituted C1-C6 alkoxy, amino, unsubstituted or substituted C1-C6 alkylamino, unsubstituted or substituted di-C1-C6 alkylamino, unsubstituted or substituted C6-C10 aryl, unsubstituted or substituted heteroaryl comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O, and S, unsubstituted or substituted C3-C10 carbocycle, or unsubstituted or substituted heterocycle comprising one or two 5- or 6-member rings and 1-4 heteroatoms selected from N, O, and S; R27 is -(alkylene)m-C3-C8 cycloalkyl, -(alkylene)m-aryl, -(alkylene)m-heterocyclo, -(alkylene)m-heteroayl, -(alkylene)m-NR3R4 , -(alkylene)m—C(O)—NR3R4, -(alkylene)m-O—R5, -(alkylene)m-S(O)n—R5, or -(alkylene)m-S(O)n—NR3R4 any of which may be optionally independently substituted with one or more Rx groups as allowed by valance, and wherein two Rx groups bound to the same or adjacent atoms may optionally combine to form a ring, providing that in (Q), R27 may also be H, C1-C3 alkyl or haloalkyl; R3 and R4 at each occurrence are independently selected from: (i) hydrogen, or (ii) alkyl, cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, or heteroarylalkyl, any of which may be optionally independently substituted with one or more Rx groups as allowed by valance, and wherein two Rx groups bound to the same or adjacent atom may optionally combine to form a ring; or R3 and R4 together with the nitrogen atom to which they are attached may combine to form a heterocyclo ring optionally independently substituted with one or more Rx groups as allowed by valance, and wherein two Rx groups bound to the same or adjacent atoms may optionally combine to form a ring; Rx at each occurrence is independently selected from halo, cyano, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkyl, -(alkylene)m-OR5, -(alkylene)m-O-alkylene-OR5, -(alkylene)m-S(O)n—R5, -(alkylene)m-NR3R4, (alkylene) m-CN, -(alkylene)m-C(O)—R5, -(alkylene)m-C(S)—R5, -(alkylene)m-C(O)—OR5, -(alkylene)m-O—C(O)—R5, -(alkylene)m-C(S)—OR5, -(alkylene)m-C(O)-(alkylene)m-NR3R4, -(alkylene)m-C(S)—NR3R4, -(alkylene)m-N(R3)-C(O)—NR3R4, -(alkylene)m-N(R3)-C(S)—NR3R4, -(alkylene)m-N(R3)-C(O)—R5, -(alkylene)m-N(R3)—(S)—R5, -(alkylene)m-O—C(O)—NR3R4, -(alkylene)m-O—C(S)—NR3R4, -(alkylene)m-SO2—NR3R4, -(alkylene)m-N(R3)—SO2—R5, -(alkylene)m-N(R3)—SO2—NR3R4, -(alkylene)m-N(R3)—C(O)—OR5, -(alkylene)m-N(R3)—C(S)—OR5, or -(alkylene)m-N(R3)—SO2—R5; wherein: said alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkyl groups may be further independently substituted with one or more -(alkylene)m-CN, -(alkylene)m-OR5*, -(alkylene)m-S(O)n—R5*, -(alkylene)m-NR3*R4*, -(alkylene)m-C(O)—R5*, -(alkylene)m-C(═S)R5*, -(alkylene)m-C(═O)OR5*, -(alkylene)m-OC(═O)—R5*, -(alkylene)m-C(S)—OR5*, -(alkylene)m-C(O)—NR3*R4*, -(alkylene)m-C(S)—NR3*R4*, -(alkylene)m-N(R3*)—C(O)—NR3*R4*, -(alkylene)m-N(R3*)—C(S)—NR3*R4*, -(alkylene)m-N(R3*)—C(O)—R5*, -(alkylene)m-N(R3*)—C(S)—R5*, -(alkylene)m-O—C(O)—NR3*R4*, -(alkylene)m-O—C(S)—NR3*R4*, -(alkylene)m-SO2—NR3*R4*, -(alkylene)m-N(R3*)—SO2—R5*, -(alkylene)m-N(R3*)—SO2—NR3*R4*, -(alkylene)m-N(R3*)—C(O)—OR5*, -(alkylene)m-N(R3*)—C(S)—OR5*, or -(alkylene)m-N(R3*)—SO2—R5*, n is 0, 1 or 2, and m is 0 or 1; and R3* and R4* at each occurrence is independently selected from: (i) hydrogen or (ii) alkyl, alkenyl, alkynyl cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, or heteroarylalkyl any of which may be optionally independently substituted with one or more Rx groups as allowed by valance; or R3* and R4* together with the nitrogen atom to which they are attached may combine to form a heterocyclo ring optionally independently substituted with one or more Rx groups as allowed by valance; and R5 and R5* at each occurrence is independently selected from: (i) hydrogen or (ii) alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, or heteroarylalkyl any of which may be optionally independently substituted with one or more Rx groups as allowed by valance; or a pharmaceutically acceptable salt thereof.
地址 Research Triangle Park NC US
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