Vitamin B.sub.12 derivatives and methods for their preparation
AssigneeBiotch Australia Pty Limited
InventorsGregory J. Russell-Jones, John F. McEwan
Life of this patent
Estimating the term…
Abstract
This invention relates to methods for preparing vitamin B.sub.12 (VB.sub.12) derivatives suitable for linking to a polymer, nanoparticle or therapeutic agent, protein or peptide. The methods involve reacting the 5'OH group of VB.sub.12 or an analogue thereof with an active carbonyl electrophile and subsequently obtaining said VB.sub.12 derivatives. The invention also relates to novel VB.sub.12 derivatives, VB.sub.12 derivatives prepared by the methods of the present invention and uses thereof in the preparation of in the preparation of polymer complexes or nanoparticles.
Claims26
A method for preparing VB.sub.12 derivatives suitable for linking to a polymer, nanoparticle or therapeutic agent, protein or peptide, comprising the steps of reacting the 5'OH group of VB.sub.12 or an analogue thereof with a bifunctional carbonyl electrophile to form an active intermediate, and subsequently reacting the intermediate with a nucleophilic spacer molecule to yield said VB.sub.12 derivative.
A method for preparing a VB.sub.12 derivative suitable for linking to a polymer, nanoparticle or therapeutic agent, protein or peptide comprising the steps of reacting a carboxylic acid spacer molecule with a bifunctional carbonyl electrophile to form an active intermediate, and subsequently reacting the 5'OH group of VB.sub.12 with the active intermediate to yield said VB.sub.12 derivative.
A VB.sub.12 derivative of the formula (I):
- VB.sub.12 -5'O--CO--NH--R.sup.1 (I)
- or a salt thereof, wherein
- R.sup.1 is C.sub.1-24 alkyl, C.sub.2-24 alkenyl, C.sub.2-24 alkynyl, C.sub.3-8 cycloalkyl, (C.sub.3-8 cycloalkyl)alkyl, amino, --(C.sub.1-12 alkyl)C(O)R.sup.2, --(C.sub.2-12 alkenyl)C(O)R.sup.2, --NHC(O)--C.sub.1-8 alkyl-C(O)NHNH.sub.2 or --CH(R.sup.3)C(O)R.sup.4 all of which are optionally substituted by one or more groups selected from amino, amido, hydroxy, alkyl, halo, haloalkyl, carboxy, alkoxycarbonyl, acetoxy, sulfanyl, aryl, arylalkyl and alkylarylalkyl,
- R.sup.2 is amino, hydroxy, C.sub.1-6 alkoxy or C.sub.2-6 alkenyloxy,
- R.sup.3 is an amino acid side chain or a derivative thereof, and
- R.sup.4 is hydroxy, C.sub.1-6 alkoxy, an amino acid or a peptide.
A VB.sub.12 derivative of the formula (II):
- VB.sub.12 -5'O--CO--R.sup.1 (II)
- or a salt thereof, wherein
- R.sup.1 is C.sub.1-24 alkyl or C.sub.2-24 alkenyl which are optionally substituted by one or more groups selected from amino, amido, hydroxy, alkyl, halo, haloalkyl, carboxy, alkoxycarbonyl, acetoxy, sulfanyl, aryl, arylalkyl and alkylarylalkyl, or
- R.sup.1 is --CH(R.sup.2)--NHR.sup.3,
- R.sup.2 is an amino acid side chain or derivative thereof, and
- R.sup.3 is hydrogen, an amine protecting group, an amino acid or a peptide.
Dependencies are inferred from the claim text.