发明名称 THERAPEUTIC COMPOUNDS AND RELATED METHODS OF USE
摘要 Salinomycin analogs and pharmaceutically acceptable compositions containing salinomycin analogs. Dosage forms and kits comprising salinomycin analogs and pharmaceutically acceptable compositions containing salinomycin analogs. Methods of using salinomycin analogs, pharmaceutically acceptable compositions, dosage forms, and kits for the treatment of proliferative diseases, e.g., cancer, or microbial infections in a subject
申请公布号 US2014371285(A1) 申请公布日期 2014.12.18
申请号 US201314370415 申请日期 2013.01.07
申请人 Sprott Kevin;Lewis Michael;Choi Hyeongwook;Fang Frank;Shan Mingde;Lazarova Tsvetelina I.;Li Lin;Siddiqui M. Arshad;Larouche-Gauthier Robin;Lemire Alexandre 发明人 Sprott Kevin;Lewis Michael;Choi Hyeongwook;Fang Frank;Shan Mingde;Lazarova Tsvetelina I.;Li Lin;Siddiqui M. Arshad;Larouche-Gauthier Robin;Lemire Alexandre
分类号 C07D493/20 主分类号 C07D493/20
代理机构 代理人
主权项 1. A compound of Formula I: wherein, R1 is —OR10, —CH2OR10, —CH2NR11R12, —C(O)R10, —C(O)OR10, —C(O)NR11R12, —OC(O)R10, —OC(O)OR10, —NR11R12, —OC(O)NR11R12, oxo, C1-C8 alkyl, C1-C8 heteroalkyl, halo, haloalkyl, cyclyl, heterocyclyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, nitro, or cyano; R1, together with R3, R5, or R6, and the atoms to which they are attached, may optionally form a heterocyclyl ring; R2 is —OR10, —SR10, —OC(O)R10, —OS(O)R10, —OC(O)OR10, —OS(O)OR10, cyano, —N3, —NR11R12, —NNR11, —OC(O)NR11R12, —SC(O)NR11R12, —P(R15R16)OR10, —OP(R15R16)OR10, —SP(R15R16)OR10, or —NHP(R15R16)OR10; L-M-T together form a structure selected from —C(R3)n—C(R3)n—C(R3)n—, —CR3═CR3—C(R3)n—, and —C(R3)n—CR3═CR3—; or L-M, M-T, or L-M-T, and one to three additional —C(R3)n—, —O—, —NR11—, or —S— to which they are bound, together form a 3-6 membered cyclyl, heterocyclyl, aryl, or heteroaryl ring, wherein n is independently 1 or 2; each R3 is independently H, halo, oxo, —OR10, —SR10, —OC(O)R10, —OS(O)R10, —OC(O)OR10, —OS(O)OR10, —OS(O)2R10, cyano, —N3, —NR11R12, —NNR11, —OC(O)NR11R12, —NR11C(O)OR12, —NR11′C(O)NR11R12, —SC(O)NR11R12, —NR11′S(O2)NR11R12, —P(R15R16)OR10, —OP(R15R16)OR10, —SP(R15R16)OR10, —NHP(R15R16)OR10, C1-C8 alkyl, C1-C8 heteroalkyl, cyclyl, heterocyclyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; R5 is H, halo, oxo, —OR10, —SR10, —OC(O)R10, —OS(O)R10, —OC(O)OR10, —OS(O)OR10, cyano, —N3, —NR11R12, —NNR11, —OC(O)NR11R12, —NR11C(O)OR12, —NR11′C(O)NR11R12, —SC(O)NR11R12, —NR11′S(O2)NR11R12, —P(R15R16)OR10, —OP(R15R16)OR10, —SP(R15R16)OR10, or —NHP(R15R16)OR10; R6 is independently H, oxo, —OR10, —SR10, —COR10, —CNR11R12, —C(O)R10, —C(O)OR10, —C(O)NR11R12, —OC(O)R10, —OS(O)R10, —OC(O)OR10, —OS(O)OR10, —NR11R12, ═NR11, —OC(O)NR11R12, —SC(O)NR11R12, halo (e.g., F, Cl, Br, I), —NH2, cyano, C1-C8 alkyl, cyclylalkyl, or aryl; R5 and R6 together may optionally form a substituted or unsubstituted 5-8 membered cyclyl, heterocyclyl, aryl, or heteroaryl ring; R7 is H, halo, C1-C8 alkyl, or C1-C8 heteroalkyl; R10 is H, substituted or unsubstituted C1-C8 alkyl, C2-C8 alkenyl, C1-C8 heteroalkyl, substituted or unsubstituted C3-C8 cyclyl, C3-C8 heterocyclyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl, or an amino acid side chain; R11, R11′, and R12 are each independently H, substituted or unsubstituted C1-C8 alkyl, C1-C8 heteroalkyl, C3-C8 cyclyl, C3-C8 heterocyclyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, —OR13, —C(O)OR13, —OC(O)R13, —C(O)R13, —S(O)R13, —S(O2)R13, —NR131R14, cyano, or an amino acid side chain; R13 and R14 are each independently H, C1-C8 alkyl, C1-C8 heteroalkyl, —C(O)R10, C3-C8 cyclyl, C3-C8 heterocyclyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, or cyano; R15 and R16 are each independently ═O, —S, —OR17, —SRN, or —NR17R18, provided R15 and R16 are not both double-bonded moieties; R17 and R18 are each independently H, C1-C8 alkyl, C1-C8 heteroalkyl, C3-C8 cyclyl, C3-C8 heterocyclyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; R19 is —O—, —S—, —NR17—, —N(OH)—, or —N(OR10)—; and q is 1 or 2; provided that when R1 is —C(O)OH, n is 2, q is 1, R6 is oxo, and R7 is methyl, R2, R3, and R5 are not all hydroxy; provided that when R1 is —C(O)OH, R6 is oxo, R7 is methyl, and R3 and R5 are hydroxy, R2 is not benzoxy or benzyloxy; and provided that when R1 is —C(O)OH, R6 is oxo, R7 is methyl, and R2 is hydroxyl, R3 or R5 are not —OCH2Cl, —OCH2Br, or —OC(O)CH2Cl.
地址 Cambridge MA US