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    • 5. 发明授权
    • Bifunctional boronic compound complexing reagents and complexes
    • 双功能硼酸化合物络合物络合物
    • US6156884A
    • 2000-12-05
    • US222468
    • 1998-12-29
    • Clarence N. AhlemRobert J. KaiserKevin P. LundMark L. Stolowitz
    • Clarence N. AhlemRobert J. KaiserKevin P. LundMark L. Stolowitz
    • C07C229/38C07C233/49C07C237/22C07C255/13C07C259/10C07C271/22C07C281/02G01N33/543C07F5/04
    • C07C233/49C07C229/38C07C237/22C07C255/13C07C259/10C07C271/22C07C281/02G01N33/54353Y10S530/81Y10S530/816
    • Reagents suitable for the modification of a bioactive species for the purpose of incorporating a bifunctional boronic compound complexing moiety for subsequent conjugation to a different (or the same) bioactive species having pendant phenylboronic acid moieties of General Formula 1, ##STR1## wherein group R is an electrophilic or nucleophilic moiety suitable for reaction of the putative bifunctional boronic compound complexing reagent with a bioactive species, wherein group R.sub.2 is selected from one of H and OH moieties, and wherein group R.sub.3 is selected from one of an alkyl and a methylene bearing an electronegative substituent. Group Z is a spacer selected from (CH.sub.2).sub.n and CH.sub.2 O(CH.sub.2 CH.sub.2 O).sub.n.sbsb.2, wherein n is an integer of from 1 to 5, and wherein n.sub.2 is an integer of from 1 to 4. Each of group Z.sub.2 and Z.sub.3 is a spacer selected from CH.sub.2 Ar, CH.sub.2 CONHCH.sub.2 Ar, CH.sub.2 CONH(CH.sub.2).sub.n.sbsb.3 CO--NHCH.sub.2 Ar, and (CH.sub.2).sub.n.sbsb.4 NHCO(CH.sub.2).sub.n.sbsb.5 CONHCH.sub.2 Ar, wherein the group Ar represents the aromatic ring in the reagent of General Formula I to which the spacer Z.sub.2 or Z.sub.3 is appended, wherein n.sub.3 is an integer of from 1 to 5, wherein n.sub.4 is an integer selected from one of 2 and 3, and wherein n.sub.5 is an integer of from 1 to 4. Reaction of a reagent of General Formula I with a bioactive species affords a conjugate having pendant putative bifunctional boronic compound complexing moieties. (one or more) The conjugate may be further reacted with hydroxylamine (NH.sub.2 OH) by amidation of the benzoic acid ester moiety to afford a class of bifunctional boronic compound complexing conjugate, e.g., conjugate with one or more pendant bifunctional boronic compound complexing moieties.
    • 用于修饰生物活性物质的试剂,其目的是将双功能硼化合物络合部分结合到具有通式1的苯基硼酸侧基的不同(或相同)生物活性物质中,其中基团R是亲电子的或 适用于推定的双功能硼化合物络合试剂与生物活性物质的反应的亲核部分,其中基团R2选自H和OH部分之一,并且其中基团R3选自具有电负性取代基的烷基和亚甲基之一。 基团Z是选自(CH 2)n和CH 2 O(CH 2 CH 2 O)n 2的间隔基,其中n是1至5的整数,并且其中n 2是1至4的整数。基团Z 2和Z 3是间隔基 选自CH 2 Ar,CH 2 CONHCH 2 Ar,CH 2 CONH(CH 2)n 3 CO-NHCH 2 Ar和(CH 2)n 4 NHCO(CH 2)n5CONHCH 2 Ar,其中基团Ar表示通式I的试剂中附着有间隔基Z2或Z3的芳环, n3是1至5的整数,其中n4是选自2和3之一的整数,并且其中n5是1至4的整数。通式I的试剂与生物活性物质的反应提供了共轭物 具有推荐的双官能硼化合物络合部分。 (一种或多种)缀合物可以通过苯甲酸酯部分的酰胺化与羟胺(NH 2 OH)进一步反应,得到一类双官能硼化合物络合缀合物,例如与一个或多个双官能硼化合物络合部分的偶联物。