发明名称 Quinolone analogs and methods related thereto
摘要 The present invention provides novel quinolone compounds and pharmaceutical composition thereof which may inhibit cell proliferation and/or induce cell apoptosis. The present invention also provides methods of preparing such compounds and compositions, and methods of making and using the same.
申请公布号 US8853234(B2) 申请公布日期 2014.10.07
申请号 US201113043956 申请日期 2011.03.09
申请人 Senhwa Biosciences, Inc. 发明人 Nagasawa Johnny Yasuo;Pierre Fabrice;Haddach Mustapha;Schwaebe Michael;Darjania Levan;Whitten Jeffrey P.
分类号 C07D498/06;C07D498/16;C07D471/14;C07D513/14 主分类号 C07D498/06
代理机构 Cooley LLP 代理人 Cooley LLP
主权项 1. A compound of Formula (I), or a pharmaceutically acceptable salt or ester thereof; wherein indicates an optionally unsaturated bond; each of B, X, A or V is absent if Z1, Z2, Z3 and Z4, respectively, is N; and each of B, X, A and V is independently H, halo, azido, —CN, —CF3, —CONR1R2, —NR1R2, —SR2, —OR2, —R3, —W, -L-W, —W0, -L-N(R)—W0, A2 or A3, when each of Z1, Z2, Z3 and Z4, respectively, is C; Z is O, S, CR42, CR4NR4, or CR4; each of Z1, Z2, Z3 and Z4 is independently C or N, provided any three N are non-adjacent; Z5 is C; or Z5 may be N when Z is N; Y is an optionally substituted 5-6 membered carbocyclic or heterocyclic ring; U1 is —C(=T)N(R)—, —C(=T)N(R)O—, or —C(=T)-, where T is O, S, or NH; or U1 may be a bond when Z5 is N or U2 is H; U2 is H, or C3-C7 cycloalkyl, C1-C10 alkyl, C1-C10 heteroalkyl, C2-C10 alkenyl or C2-C10 heteroalkenyl group, each of which may be optionally substituted with one or more halogens, ═O, or an optionally substituted 3-7 membered carbocyclic; or U2 is -L-W, -L-N(R)—W0, or A2; in each —NR1R2, R1 and R2 together with N may form an optionally substituted azacyclic ring, optionally containing an additional heteroatom selected from N, O and S as a ring member; R1 is H or C1-C6 alkyl, optionally substituted with one or more halogens, or ═O; R2 is H, or C1-C10 alkyl, C1-C10 heteroalkyl, C2-C10 alkenyl, or C2-C10 heteroalkenyl, each of which may be optionally substituted with one or more halogens, ═O, or an optionally substituted 3-7 membered carbocyclic or heterocyclic ring; R3 is an optionally substituted C1-C10 alkyl, C2-C10 alkenyl, C5-C10 aryl, or C6-C12 arylalkyl, or a heteroform of one of these, each of which may be optionally substituted with one or more halogens, ═O, or an optionally substituted 3-6 membered carbocyclic or heterocyclic ring; each R4 is independently H, or C1-C6 alkyl; or R4 may be —W, -L-W or -L-N(R)—W0; each R and R0 is independently H or C1-C6 alkyl; L is a C1-C10 alkylene, C1-C10 heteroalkylene, C2-C10 alkenylene or C2-C10 heteroalkenylene linker, each of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, oxo (═O), or C1-C6 alkyl; W is an optionally substituted 4-7 membered azacyclic ring, optionally containing an additional heteroatom selected from N, O and S as a ring member; W0 is an optionally substituted 3-4 membered carbocyclic ring, or a C1-C6 alkyl group substituted with from 1 to 4 fluorine atoms; provided one of V, A, X and B is a secondary amine A2 or a tertiary amine A3, wherein the secondary amine A2 is —NH—W0, and the tertiary amine A3 is a fully saturated and optionally substituted six-membered or seven-membered azacyclic ring optionally containing an additional heteroatom selected from N, O or S as a ring member, or the tertiary amine A3 is a partially unsaturated or aromatic optionally substituted five-membered azacyclic ring, optionally containing an additional heteroatom selected from N, O or S as a ring member; with the proviso that when Z1 is N, Z2 and Z4 are C, Z5 is C, U1 is —C(O)NH—, U2 is -L-W, and L is an ethylene linker, one of V, A, and X is independently an optionally substituted aryl, heteroaryl, or 7-membered azacyclic ring, optionally containing an additional heteroatom selected from N, O and S as a ring member, if W is pyrrolidin-1-yl, N-methyl-pyrrolidin-2-yl, piperidin-1-yl or morpholin-1-yl.
地址 New Taipei TW