发明名称 BENZOPYRYLIUM COMPOUNDS
摘要 Compounds used as labels with properties comparable to known fluorescent compounds. The compounds are conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.
申请公布号 US2015322078(A1) 申请公布日期 2015.11.12
申请号 US201314411447 申请日期 2013.08.20
申请人 Hermanson Greg;Czerney Peter T.;Desai Surbhi;Wenzel Matthias S.;Lehmann Frank G.;Nlend Marie Christine 发明人 Hermanson Greg;Czerney Peter T.;Desai Surbhi;Wenzel Matthias S.;Lehmann Frank G.;Nlend Marie Christine
分类号 C07D491/147;G01N33/58;C07D491/052;A61K49/00;C07D405/06;C07D405/14 主分类号 C07D491/147
代理机构 代理人
主权项 1. A compound according to any of general formula Iawherein each of R1, R2, R3, R4, R5, R6, R11, and R12 is the same or different and is independently selected from H, SO3, Z, L-Z, a PEG group P-L-Z where P is an ethylene glycol group, a diethylene glycol group, or a polyethylene glycol group, where the polyethylene glycol group is (CH2CH2O)s, where s is an integer from 3-6 inclusive, a sulfonamide group -L-SO2NH—P-L-Z, a caboxamide group -L-CONH—P-L-Z, hydrogen, alkyl-, tert-alkyl, aryl-, carboxyaryl-, dicarboxyaryl, heteroaryl-, cycloalkyl-, heterocycloalkyl-, alkyloxy-, alkylmercapto- with alkyl and cycloalkyl including olefin linkage residues, aryloxy-, arylmercapto-, heteroaryloxy-, heteroarylmercapto-, hydroxy-, nitro-, a carboxylic acid, an amino group, or cyano residues; where L is a divalent linear (—(CH2)t—, t=0 to 15), branched, or cyclic alkane group that can be substituted by at least one atom of oxygen, nitrogen, substituted nitrogen, and/or sulfur; where Z is H, CH3, alkyl group, sulfoalkyl, heteroalkyl group, NH2, —COO−, —COOH, —COSH, CO—NH—NH2, —COF, —COCl, —COBr, —COI, —COO-Su (succinimidyl/sulfosuccinimidyl), —COO-STP (4-sulfo-2,3,5,6-tetrafluorophenyl), —COO-TFP (2,3,5,6-tetrafluorophenyl), —COO-benzotriazole, —CO-benzotriazole, —CONR′—CO—CH2—I, —CONR′R″, —CONR′-biomolecule, —CONR′-L-COO−, —CONR′-L-COOH, —CONR′-L-COO-Su, —CONR′-L-COO-STP, —CONR′-L-COO-TFP, —CONR′-L-CONR″2, —CONR′-L-CO-biomolecule, —CONR′-L-CO—NH—NH2, —CONR′-L-OH, —CONR′-L-O-phosphoramidite, —CONR′-L-CHO, —CONR′-L-maleimide, or —CONR′-L-NH—CO—CH2—I; each of R′ and R″ is selected from H, aliphatic group, or heteroaliphatic group, and the biomolecule is a protein, peptide, antibody, nucleotide, oligonucleotide, biotin, or hapten; X is selected from —OH, —SH, —NH2, —NH—NH2, —F, —Cl, —Br, I, —NHS (hydroxysuccinimidyl/sulfosuccinimidyl), —O-TFP (2,3,5,6-tetrafluorophenoxy), —O-STP (4-sulfo-2,3,5,6-tetrafluorophenoxy), —O-benzotriazole, -benzotriazole, —NR-L-OH, —NR-L-O-phosphoramidite, —NR-L-SH, —NR-L-NH2, —NR-L-NH—NH2, —NR-L-CO2H, —NR-L-CO—NHS, —NR-L-CO-STP, —NR-L-CO-TFP, —NR-L-CO-benzotriazole, —NR-L-CHO, —NR-L-maleimide, or —NR-L-NH—CO—CH2-I, where R is —H or an aliphatic or heteroaliphatic group; each of R10, R13, and R14 is the same or different and is independently selected from aliphatic, heteroaliphatic, sulfoalkyl group, carboxyalkyl group, heteroaliphatic with terminal SO3, Z, L-Z, PEG group P-L-Z where P is an ethylene glycol group, a diethylene glycol group, or a polyethylene glycol group where the polyethylene glycol group is (CH2CH2O)s, where s is an integer from 3-6 inclusive, a sulfonamide group -L-SO2NH—P-L-Z, or a caboxamide group -L-CONH—P-L-Z; each of R7 and R9 is the same or different and is independently hydrogen, aliphatic group, heteroaliphatic group, or PEG group P-L-Z where P is selected from an ethylene glycol group, a diethylene glycol group, or a polyethylene glycol group where the polyethylene glycol group is (CH2CH2O)s, where s is an integer from 3-6 inclusive; or R7 and R9 together form a cyclic structure where R3 and R4 are joined using a divalent structural element selected from —(CH2)q—, —(CH2)qO(CH2)q′—, —(CH2)qS(CH2)q′—, —(CH2)qCH═CH—, —OCH═CH— where each of q and q′ is the same or different and is a integer from 1 to 6 inclusive; and R8 is selected from hydrogen, alkyl, sulfoalkyl, fluorine, chlorine, bromine, and PEG group P-L-Z where P is selected from an ethylene glycol group, a diethylene glycol group, or a polyethylene glycol group, where the polyethylene glycol group is (CH2CH2O)s, where s is an integer from 3-6 inclusive; each of R1 and R2, R2 and R3, R3 and R4, R5 and R6, R5 and R8, R9 and R10, R11 and R12, or R12 and R13 may form one or more aliphatic, heteroaliphatic or aromatic rings, and where the resultant ring(s) is optionally substituted by at least one alkyl-, sulfoalkyl, tert-alkyl, aryl-, carboxyaryl-, dicarboxyaryl, heteroaryl-, cycloalkyl-, heterocycloalkyl-, alkyloxy-, alkylmercapto- with alkyl and cycloalkyl including olefin linkage residues, aryloxy-, arylmercapto-, heteroaryloxy-, heteroarylmercapto-, hydroxy-, nitro-, sulfonic acid, a carboxylic acid, an amino group, or cyano residues; at least one of R1-R14 optionally contains in addition to at least one PEG an additional solubilizing, ionizing, or ionized substituent selected from SO3−, PO32−, CO2H, OH, NR3+, cyclodextrins or sugars providing hydrophilic characteristics; the substituents optionally linked to chromophore by an aliphatic or heteroaliphatic or cyclical spacer; Kat is a number of Na+, K+, Ca2+, ammonia, or other cation(s) needed to compensate the negative charge(s); n is 0, 1, 2, or 3; o is an integer from 0 to 12 inclusive; and p is an integer from 1 to 6 inclusive.
地址 Loves Park IL US