Chlorambucil, structure

According to a hypothesis launched by Larionov et al in the 1960s, some new nitrogen mustard derivatives were developed. They contain metabolites and heterocyclic structures as carriers of the cytotoxic chloroethylamine groups. By this way the synthesis of aliylating metabolites started melphalan (sarcolysine) as L- or DL-phenylalanine derivative prospidine with a tricyclic piperazine moiety and chlorambucil as butyric acid derivative. It was proven that each alkylating metabolite has its own spectrum of selective antitumor activity. 

Fig. 3.11 Alkylating polyamide binding site model and structures of polyamide-alkylator conjugates. The dotted triangle represents the alkylating agent. All other symbols are defined in Fig. 3.4. The CBI and chlorambucil alkylator domains are boxed...

Melphalan Melphalan, L-3-[p-[bis-(2-chloroethyl)amino]phenyl]alanine (30.2.1.13), is a structural analog of chlorambucil in which the butyric acid fragment is replaced with an aminoacid fragment, alanine. This drug is synthesized from L-phenylalanine, the nitration of... 

Chemical Name Prednisolone 21 -(4 -(p-bis(2-chloroethyl)aminol phenyl] butyrate Common Name Prednisolone chlorambucil ester Structural Formula ... 

Agents acting by an Sn 2 mechanism can be more selective in the nucleophile sites they attack, since they form transition complexes with some molecules more readily than with others. Other agents in vivo may, because of their chemical structure, concentrate in certain areas, giving effects not predicted from model experiments. This is the case with dimethylmyleran, a sulphonoxyalkane, quite unreactive to nucleophiles in vitro, but quite toxic in vivo. Presumably this is due to its reaction with nucleophiles, which are in the lipid phase where it concentrates. Similarly the biological activity of the aromatic nitrogen mustard chlorambucil is considerably influenced by complexing with serum proteins. 

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