发明名称 BIOCONJUGATES OF CYANINE DYES
摘要 Compounds are disclosed that are useful for noninvasive imaging in the near-infrared spectral range. Bioconjugate cyanine compounds of Formula II are presented:;;wherein Q is a portion of a polymethine bridge selected from the group consisting of:;
申请公布号 US2015119553(A1) 申请公布日期 2015.04.30
申请号 US201414552396 申请日期 2014.11.24
申请人 LI-COR, INC. 发明人 Xu Xinshe;Draney Daniel R.;Cheung Lael
分类号 A61K49/00;G01N33/58;C08B37/08;C07F9/6561;C07D471/04;C07K19/00 主分类号 A61K49/00
代理机构 代理人
主权项 1. A bioconjugate compound of Formula II: wherein QL is a portion of a polymethine bridge selected from the group consisting of: wherein QL is the central portion of either a five- or a seven-polymethine-carbon polymethine bridge; each R1 is a member independently selected from the group consisting of -L-Y—Z and alkyl that is additionally substituted with from 0 to 1 R13 and from 0 to 1 RL; wherein the alkyl is optionally interrupted by at least one heteroatom; each R2a and R2b is a member independently selected from the group consisting of alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, amidoalkyl, alkylthioalkyl, carboxyalkyl, alkoxycarbonylalkyl, and sulfonatoalkyl; wherein a carbon of the member is additionally substituted with from 0 to 1 RL; or, alternatively, a R2a and R2b pair, together with the ring carbon to which the R2a and R2b are bonded, join to form a spirocycloalkyl ring, wherein the spirocycloalkyl ring is additionally substituted with from 0 to 6 R14 and from 0 to 1 RL, or an exocyclic alkene, wherein the exocyclic alkene is additionally substituted with from 0 to 2 R14 and from 0 to 1 RL; each R3, R4a, R4b, R5a, R5b, R6a, and R6b is a member independently selected from the group consisting of hydrogen, alkyl, alkenyl, halo, hydroxyl, alkoxy, amino, cyano, carboxyl, alkoxycarbonyl, amido, sulfonato, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, and sulfonatoalkyl; wherein a carbon of the member is additionally substituted with from 0 to 1 RL; or, alternatively, a pair of said members that is selected from the group consisting of R3 and R4a, an R4a and R5a, and an R5a and R6a, together with the pair of atoms to which the pair of said members is bonded, joins to form an aryl ring, wherein the aryl ring is additionally substituted with from 0 to 2 R14 and from 0 to 1 RL; each R7 is a member independently selected from the group consisting of hydrogen and alkyl; wherein the alkyl is additionally substituted with from 0 to 3 R14 and from 0 to 1 RL; or, alternatively, both R7, together with the intervening segment of the polyene to which both R7 are bonded, join to form a ring, wherein said ring is selected from the group consisting of a cycloalkyl and a heterocyclyl ring; wherein the ring is additionally substituted with from 0 to 3 R14 and from 0 to 1 RL; R8, R9, R10, R11, and R12 are each a member independently selected from the group consisting of hydrogen, alkyl, alkenyl, halo, alkoxy, sulfonato, hydroxyl, amino, carboxyl, alkoxycarbonyl, cyano, amido, thioacetyl, and -L-Y—Z; wherein, if present, at least one member selected from the group consisting of R8, R9, and R10 is -L-Y—Z; each R13 is a member independently selected from the group consisting of hydroxyl, amino, carboxyl, alkoxycarbonyl, cyano, amido, sulfonato, and thioacetyl; each R14 is a member independently selected from the group consisting of alkyl, alkenyl, halo, hydroxyl, alkoxy, amino, cyano, carboxyl, alkoxycarbonyl, amido, sulfonato, alkoxycarbonylalkyl, and alkoxyalkyl; wherein the alkyl or alkenyl is additionally substituted with from 0 to 1 R13 and from 0 to 1 RL; each L is an optional member independently selected from the group consisting of a bond, a C1-C20 alkylene, and a C1-C20 alkenylene; wherein the alkylene or alkenylene is optionally interrupted by at least one heteroatom; each Y is an optional member independently selected from the group consisting of a bond, —O—, —S—, —NH—, —NHC(O)—, —C(O)NH—, —NR15—, —NR15C(O)—, —C(O)NR15—, —N(Z)—, —N(Z)C(O)—, and —C(O)N(Z)—; each Z is independently selected from the group consisting of -L-R13 and -L-RL; alternatively, —Y—Z is a member selected from the group consisting of —N(Z)2, —N(Z)C(O)Z, and —C(O)N(Z)2, and the two Z groups may optionally be linked to form a cycloalkynyl group; each R15 is a member independently selected from the group consisting of alkyl and alkoxycarbonylalkyl, wherein the alkyl is optionally interrupted by at least one heteroatom; each RL comprises a linking group and a biomolecule connected thereby, wherein the compound comprises at least one RL; wherein the biomolecule is selected from the group consisting of hyaluronan, a tetracycline derivative, avidin, biotin, streptavidin, a peptide, and a protein; and wherein said compound has a balanced charge.
地址 Lincoln NE US