Derivatisation of biological molecules

摘要

The present disclosure relates to a new polymerisation process in which ethylenically unsaturated monomers are polymerised by a living radical polymerisation process in the presence of an initiator and a catalyst. Polymers produced by this new process are also thought to be novel and may be used to derivatise biological molecules to improve their efficacy as therapeutic treatments. A preferred polymer is of formula;
The polymers are particularly suitable for derivatising proteins, such as interferon-α.

主权项

1. A compound of general formula XII or XIII wherein Groups M are the same or different and are residues of ethylenically unsaturated monomers; f is 1 to 500; x is 1 or 2; p is 1-5; R1 is an electron-withdrawing group selected from the group consisting of a keto group, an ester group, and a sulphone group; R2 is selected from C═O, C(═O)NR9 or a bond; wherein R9 is H or C1-4 alkyl; R3 is selected from the group consisting of C1-C20 alkylene, C3-C8 cycloalkylene, C(═O)R10, C(═O)NR11, C1-C20 alkoxy, C2-C20 alkenylene, C2-C20 alkenyl oxiranylene, arylene, heterocyclene and aralkylene; in which 0 to all of the hydrogen atoms are replaced with halogen, C1-C6 alkyl optionally substituted with 1 to 2 substituents selected from the group consisting of C1-C4 alkoxy, aryl, heterocyclyl, C(═O)R13, C(═O)NR11R12, oxiranyl and glycidyl; R10 is alkylene of from 1 to 20 carbon atoms, alkoxy from 1 to 20 carbon atoms, oligo(alkoxy) in which each alkoxy group has from 1 to 3 carbon atoms, aryloxy or heterocyclyloxy; any of which groups may have substituents selected from optionally substituted alkoxy, oligoalkoxy, amino (including mono- and di-alkyl amino and trialkyl ammonium, which alkyl groups, in turn, may have substituents selected from acyl, alkoxycarbonyl, alkenoxycarbonyl, aryl and hydroxy) and hydroxyl groups; R11 and R12 are independently H or alkyl of from 1 to 20 carbon atoms, or R11 and R12 may be joined together to form an alkanediyl group of from 2 to 5 carbon atoms, thus forming a 3- to 6-membered ring; R4 and R5 are each independently selected from H, Z, halogen, C1-20 alkyl, C3-C8 cycloalkyl, OH, CN, C2-C20 alkenyl, C2-C20 alkenyl oxiranyl, C(═O)R13, glycidyl, aryl, heterocyclyl, arylkyl, aralkenyl, in which 0 to all of the hydrogen atoms are replaced with halogen, C1-C6 alkyl optionally substituted with 1 to 2 substituents selected from the group consisting of C1-C4 alkoxy, aryl, heterocyclyl, C(═O)R13, C(═O)NR11R12, oxiranyl and glycidyl; where R13 is alkyl of from 1 to 20 carbon atoms, alkoxy of from 1 to 20 carbon atoms, oligo(alkoxy) in which each alkoxy group has 1 to 3 carbon atoms, aryloxy or heterocyclyloxy any of which groups may have substituents selected from optionally substituted alkoxy, oligoalkoxy, amino (including mono- and di-alkyl amino and trialkyl ammonium, which alkyl groups, in turn may have substituents selected from acyl, alkoxycarbonyl, alkenoxycarbonyl, aryl and hydroxy) and hydroxyl groups; and L is a linking group; Z is selected from the group consisting of Cl, Br, I, OR14, SR15, SeR15, OP(═O)R15, OP(═O)(═OR15)2, O—N(R15)2 and S—C(═S)N(R15)2, where R14 is alkyl of from 1 to 20 carbon atoms in which each of the hydrogen atoms may be independently replaced by halide, R15 is aryl or a straight or branched C1-C20 alkyl group, and where an N(R15)2 group is present, the two R15 groups may be joined to form a 5- or 6-membered heterocyclic ring; T is a conjugated biological molecule, the biological molecule being selected from the group consisting of a peptide, a protein and a lipoprotein; and D is S, NH or O.