Water‐soluble polyamides as potential drug carriers, II. Amine‐functionalized poly (α,β‐d,l‐aspartamide) derivatives

Several derivatives of poly(α,β‐D,L‐aspartic acid) ( 2 ) comprising amine functions as side chain components are synthesized for use as macromolecular drug carriers. The structures of the target polymers are designed so as to provide complete solubility in water, a prerequisite for smooth intravenous administration, and the strategy of derivatization reflects the requirement for the performance of all reaction steps in a partially or entirely aqueous phase. The poly(aspartic acid) ( 2 ) — a known synthetic polyamide obtained from poly(succinimide) ( 1 ) and composed of both α‐ and β‐ peptide units in the chain — is coupled with ethylenediamine, diethylenetriamine, N‐(2‐hydroxyethyl)ethylenediamine, and hydrazine, respectively, in the presence of water‐soluble carbodiimides. This gives the poly(aspartamides) 3 to 6 possessing primary amino side groups. More efficaciously, circumventing the intermediacy of the polyacid 2 , polymers 3 to 6 are obtained through nucleophilic opening of the imide rings in 1 by the same amine reactants. The analytically and spectroscopically characterized, water‐soluble target polymers 3 to 6 have inherent viscosities ranging from 5 to 20 ml g −1 and possess the structural prerequisites for side‐chain drug anchoring involving the spacer‐bound amino groups. The susceptibility of these functional groups to substitution as a measure of their drug binding capabilities is demonstrated by conversion of 5 and 6 to the N‐acryloylated derivatives 7 and 8 — with 7 further derivatized to give 9 — and by condensation of 5‐formylsalicylic acid with the bidentate — ethylenediamine side group in 4 to give the conjugate 10 containing the bioactive salicylyl group as a side‐chain component.